Cancer Immunology, Immunotherapy

, Volume 52, Issue 12, pp 715–738

Naturally occurring B-cell responses to breast cancer

Review

Abstract

As demonstrated by the effectiveness of trastuzumab, antibodies against breast cancer antigens are a potentially potent mechanism of tumor control. While trastuzumab is administered exogenously, its efficacy suggests that induction of very high titer antibody responses in vivo might also be therapeutic. Both naturally occurring and vaccine-induced antibody responses to some breast cancer antigens are associated with improved survival in some cases. However, the improvement in survival associated with antibody responses to breast cancer is modest, and tumor regression is not known to be associated with the natural antitumor antibody response, indicating a need for improved understanding of the natural antitumor antibody response. Naturally occurring B-cell responses in the form of serum antibody, tumor reactive lymph node B cells, and tumor-infiltrating B cells have been described, and a variety of breast tumor–associated antigens have been identified based on reactivity of patient antibodies. This review discusses current knowledge of humoral immunity to breast cancer with regard to specific antigens and the basis for their immunogenicity, and the contexts (tumor, lymph node, serum) in which responses are observed. With few exceptions, "tumor-associated antigens" identified with naturally occurring antibodies may be overexpressed on tumor but are in fact nonspecific autoantigens. This suggests that while overexpression or aberrant processing can increase immunogenicity in some cases, the immunogenicity of many or even most tumor-associated antigens is a function of expression in tumor or the result of ancillary tumor factors.

Keywords

Antibody B cell Breast cancer 

References

  1. 1.
    Baselga J (2001) Phase I and II clinical trials of trastuzumab. Ann Oncol 12:S49Google Scholar
  2. 2.
    Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J, Norton L (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344:783Google Scholar
  3. 3.
    Ross MB, Buzdar AU, Hortobagyi GN, Lukeman JM (1982) Spontaneous regression of breast carcinoma: follow-up report and literature review. J Surg Oncol 19:22PubMedGoogle Scholar
  4. 4.
    Hodenpyl E (1910) Treatment of carcinoma with the body fluids of a recovered case. Med Rec 77:359Google Scholar
  5. 5.
    Lee YT, Sheikh KM, Quismorio FP Jr, Friou GJ (1985) Circulating anti-tumor and autoantibodies in breast carcinoma: relationship to stage and prognosis. Breast Cancer Res Treat 6:57PubMedGoogle Scholar
  6. 6.
    Sheikh KM, Quismorio FP, Friou GJ, Lee YT (1979) Ductular carcinoma of the breast: serum antibodies to tumor-associated antigens. Cancer 44:2083PubMedGoogle Scholar
  7. 7.
    Schiffman K, Rinn K, Disis ML (2002) Delayed type hypersensitivity response to recall antigens does not accurately reflect immune competence in advanced stage breast cancer patients. Breast Cancer Res Treat 74:17CrossRefPubMedGoogle Scholar
  8. 8.
    Brydak LB, Guzy J, Starzyk J, Machala M, Gozdz SS (2001) Humoral immune response after vaccination against influenza in patients with breast cancer. Support Care Cancer 9:65CrossRefPubMedGoogle Scholar
  9. 9.
    Hansen MH, Nielsen HV, Ditzel HJ (2002) Translocation of an intracellular antigen to the surface of medullary breast cancer cells early in apoptosis allows for an antigen-driven antibody response elicited by tumor-infiltrating B cells. J Immunol 169:2701PubMedGoogle Scholar
  10. 10.
    Hansen MH, Nielsen H, Ditzel HJ (2001) The tumor-infiltrating B cell response in medullary breast cancer is oligoclonal and directed against the autoantigen actin exposed on the surface of apoptotic cancer cells. Proc Natl Acad Sci U S A 98:12659CrossRefPubMedGoogle Scholar
  11. 11.
    Bondanza A, Zimmermann VS, Dell'Antonio G, Dal Cin E, Capobianco A, Sabbadini MG, Manfredi AA, Rovere-Querini P (2003) Cutting edge: dissociation between autoimmune response and clinical disease after vaccination with dendritic cells. J Immunol 170:24PubMedGoogle Scholar
  12. 12.
    Disis ML, Pupa SM, Gralow JR, Dittadi R, Menard S, Cheever MA (1997) High-titer HER-2/neu protein-specific antibody can be detected in patients with early-stage breast cancer. J Clin Oncol 15:3363PubMedGoogle Scholar
  13. 13.
    Disis ML, Knutson KL, Schiffman K, Rinn K, McNeel DG (2000) Pre-existent immunity to the HER-2/neu oncogenic protein in patients with HER-2/neu overexpressing breast and ovarian cancer [In Process Citation]. Breast Cancer Res Treat 62:245CrossRefPubMedGoogle Scholar
  14. 14.
    von Mensdorff-Pouilly S, Gourevitch MM, Kenemans P, Verstraeten AA, Litvinov SV, van Kamp GJ, Meijer S, Vermorken J, Hilgers J (1996) Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours. Eur J Cancer 32A:1325PubMedGoogle Scholar
  15. 15.
    von Mensdorff-Pouilly S, Petrakou E, Kenemans P, van Uffelen K, Verstraeten AA, Snijdewint FG, van Kamp GJ, Schol DJ, Reis CA, Price MR, Livingston PO, Hilgers J (2000) Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides and n-acetylgalactosamine (GalNAc) peptides. Int J Cancer 86:702CrossRefPubMedGoogle Scholar
  16. 16.
    Reilly RT, Machiels JP, Emens LA, Ercolini AM, Okoye FI, Lei RY, Weintraub D, Jaffee EM (2001) The collaboration of both humoral and cellular HER-2/neu-targeted immune responses is required for the complete eradication of HER-2/neu- expressing tumors. Cancer Res 61:880PubMedGoogle Scholar
  17. 17.
    Chung MH, Gupta RK, Hsueh E, Essner R, Ye W, Yee R, Morton DL (2003) Humoral immune response to a therapeutic polyvalent cancer vaccine after complete resection of thick primary melanoma and sentinel lymphadenectomy. J Clin Oncol 21:313CrossRefPubMedGoogle Scholar
  18. 18.
    DiFronzo LA, Gupta RK, Essner R, Foshag LJ, O'Day SJ, Wanek LA, Stern SL, Morton DL (2002) Enhanced humoral immune response correlates with improved disease-free and overall survival in American Joint Committee on Cancer stage II melanoma patients receiving adjuvant polyvalent vaccine. J Clin Oncol 20:3242PubMedGoogle Scholar
  19. 19.
    Coronella JA, Spier C, Welch M, Trevor KT, Stopeck AT, Villar H, Hersh EM (2002) Antigen-driven oligoclonal expansion of tumor-infiltrating B cells in infiltrating ductal carcinoma of the breast. J. Immunology 169:1829Google Scholar
  20. 20.
    Kim HJ, Krenn V, Steinhauser G, Berek C (1999) Plasma cell development in synovial germinal centers in patients with rheumatoid and reactive arthritis. J Immunol 162:3053PubMedGoogle Scholar
  21. 21.
    Colombo M, Dono M, Gazzola P, Roncella S, Valetto A, Chiorazzi N, Mancardi GL, Ferrarini M (2000) Accumulation of clonally related B lymphocytes in the cerebrospinal fluid of multiple sclerosis patients. J Immunol 164:2782PubMedGoogle Scholar
  22. 22.
    Stott DI, Hiepe F, Hummel M, Steinhauser G, Berek C (1998) Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease: the salivary glands of patients with Sjogren's syndrome. J Clin Invest 102:938PubMedGoogle Scholar
  23. 23.
    Jaume JC, Portolano S, Prummel MF, McLachlan SM, Rapoport B (1994) Molecular cloning and characterization of genes for antibodies generated by orbital tissue-infiltrating B-cells in Graves' ophthalmopathy. J Clin Endocrinol Metab 78:348PubMedGoogle Scholar
  24. 24.
    Rossen RD, Reisberg MA, Hersh EM, Gutterman JU (1977) The C1q binding test for soluble immune complexes: clinical correlations obtained in patients with cancer. J Natl Cancer Inst 58:1205PubMedGoogle Scholar
  25. 25.
    Sahin U, Tureci O, Schmitt H, Cochlovius B, Johannes T, Schmits R, Stenner F, Luo G, Schobert I, Pfreundschuh M (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proc Natl Acad Sci U S A 92:11810PubMedGoogle Scholar
  26. 26.
    Pupa SM, Menard S, Andreola S, Colnaghi MI (1993) Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients. Cancer Res 53:5864PubMedGoogle Scholar
  27. 27.
    Rughetti A, Turchi V, Ghetti CA, Scambia G, Panici PB, Roncucci G, Mancuso S, Frati L, Nuti M (1993) Human B-cell immune response to the polymorphic epithelial mucin. Cancer Res 53:2457PubMedGoogle Scholar
  28. 28.
    Bogoch S, Bogoch ES, Fager CA, Harris JH, Ambrus JL, Lux WE, Ransohoff JA (1982) Determination of anti-malignin antibody and malignin in 1,026 cancer patients and controls: relation of antibody to survival. J Med 13:49PubMedGoogle Scholar
  29. 29.
    Bogoch S, Bogoch ES (1991) Malignin antibody and early malignancy. Lancet 337:977Google Scholar
  30. 30.
    De Camilli P, Thomas A, Cofiell R, Folli F, Lichte B, Piccolo G, Meinck HM, Austoni M, Fassetta G, Bottazzo G et al (1993) The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer. J Exp Med 178:2219PubMedGoogle Scholar
  31. 31.
    Folli F, Solimena M, Cofiell R, Austoni M, Tallini G, Fassetta G, Bates D, Cartlidge N, Bottazzo GF, Piccolo G et al (1993) Autoantibodies to a 128-kd synaptic protein in three women with the stiff-man syndrome and breast cancer. N Engl J Med 328:546CrossRefPubMedGoogle Scholar
  32. 32.
    Forti S, Scanlan MJ, Invernizzi A, Castiglioni F, Pupa S, Agresti R, Fontanelli R, Morelli D, Old LJ, Pupa SM, Menard S (2002) Identification of breast cancer-restricted antigens by antibody screening of SKBR3 cDNA library using a preselected patient's serum. Breast Cancer Res Treat 73:245CrossRefPubMedGoogle Scholar
  33. 33.
    Sioud M, Hansen MH (2001) Profiling the immune response in patients with breast cancer by phage-displayed cDNA libraries. Eur J Immunol 31:716CrossRefPubMedGoogle Scholar
  34. 34.
    Jager E, Stockert E, Zidianakis Z, Chen YT, Karbach J, Jager D, Arand M, Ritter G, Old LJ, Knuth A (1999) Humoral immune responses of cancer patients against "Cancer-Testis" antigen NY-ESO-1: correlation with clinical events. Int J Cancer 84:506CrossRefPubMedGoogle Scholar
  35. 35.
    Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177PubMedGoogle Scholar
  36. 36.
    Strasser F, Betticher DC, Suter TM (2001) Trastuzumab and breast cancer. N Engl J Med 345:996.Google Scholar
  37. 37.
    Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U et al (1985) Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 230:1132PubMedGoogle Scholar
  38. 38.
    Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK (1993) Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24:85PubMedGoogle Scholar
  39. 39.
    Disis ML, Cheever MA (1997) HER-2/neu protein: a target for antigen-specific immunotherapy of human cancer. Adv Cancer Res 71:343PubMedGoogle Scholar
  40. 40.
    Disis ML, Calenoff E, McLaughlin G, Murphy AE, Chen W, Groner B, Jeschke M, Lydon N, McGlynn E, Livingston RB et al (1994) Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer. Cancer Res 54:16PubMedGoogle Scholar
  41. 41.
    Visco V, Bei R, Moriconi E, Gianni W, Kraus MH, Muraro R (2000) ErbB2 immune response in breast cancer patients with soluble receptor ectodomain. Am J Pathol 156:1417PubMedGoogle Scholar
  42. 42.
    Jasinska J, Wiltschke C, Brodowicz T, Zielinski CC, Hoffmann-Sommergruber K, Zeillinger R (1998) Anti-HER-2/neu antibodies detected in sera of patients with breast cancer, but also in healthy females. Eur J Cancer 34:2135CrossRefPubMedGoogle Scholar
  43. 43.
    Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, Slamon DJ, Murphy M, Novotny WF, Burchmore M, Shak S, Stewart SJ, Press M (2002) Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 20:719CrossRefPubMedGoogle Scholar
  44. 44.
    Pupa SM, Menard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI (1993) The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene 8:2917PubMedGoogle Scholar
  45. 45.
    Shokat KM, Goodnow CC (1995) Antigen-induced B-cell death and elimination during germinal-centre immune responses. Nature 375:334PubMedGoogle Scholar
  46. 46.
    Han S, Zheng B, Dal Porto J, Kelsoe G (1995) In situ studies of the primary immune response to (4-hydroxy-3- nitrophenyl)acetyl. IV. Affinity-dependent, antigen-driven B cell apoptosis in germinal centers as a mechanism for maintaining self- tolerance. J Exp Med 182:1635PubMedGoogle Scholar
  47. 47.
    Pietras RJ, Pegram MD, Finn RS, Maneval DA, Slamon DJ (1998) Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 17:2235CrossRefPubMedGoogle Scholar
  48. 48.
    Jurianz K, Maslak S, Garcia-Schuler H, Fishelson Z, Kirschfink M (1999) Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2. Immunopharmacology 42:209PubMedGoogle Scholar
  49. 49.
    Baselga J, Albanell J (2001) Mechanism of action of anti-HER2 monoclonal antibodies. Ann Oncol 12: S35Google Scholar
  50. 50.
    Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA, Slamon DJ (1998) Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185HER2/neu monoclonal antibody plus cisplatin in patients with HER2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 16:2659PubMedGoogle Scholar
  51. 51.
    Tokuda Y, Ohnishi Y, Shimamura K, Iwasawa M, Yoshimura M, Ueyama Y, Tamaoki N, Tajima T, Mitomi T (1996) In vitro and in vivo anti-tumour effects of a humanised monoclonal antibody against c-erbB-2 product. Br J Cancer 73:1362PubMedGoogle Scholar
  52. 52.
    Fleming GF, Meropol NJ, Rosner GL, Hollis DR, Carson WE, 3rd, Caligiuri M, Mortimer J, Tkaczuk K, Parihar R, Schilsky RL, Ratain MJ (2002) A phase I trial of escalating doses of trastuzumab combined with daily subcutaneous interleukin 2: report of cancer and leukemia group B 9661. Clin Cancer Res 8:3718PubMedGoogle Scholar
  53. 53.
    De Santes K, Slamon D, Anderson SK, Shepard M, Fendly B, Maneval D, Press O (1992) Radiolabeled antibody targeting of the HER-2/neu oncoprotein. Cancer Res 52:1916PubMedGoogle Scholar
  54. 54.
    Murray JL, Gillogly ME, Przepiorka D, Brewer H, Ibrahim NK, Booser DJ, Hortobagyi GN, Kudelka AP, Grabstein KH, Cheever MA, Ioannides CG (2002) Toxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369–377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer. Clin Cancer Res 8:3407PubMedGoogle Scholar
  55. 55.
    Yip YL, Ward RL (2002) Anti-ErbB-2 monoclonal antibodies and ErbB-2-directed vaccines. Cancer Immunol Immunother 50:569CrossRefPubMedGoogle Scholar
  56. 56.
    Nyhus JK, Wolford CC, Friece CR, Nelson MB, Sampsel JW, Barbera-Guillem E (2001) IgG-recognizing shed tumor-associated antigens can promote tumor invasion and metastasis. Cancer Immunol Immunother 50:361CrossRefPubMedGoogle Scholar
  57. 57.
    Lancaster CA, Peat N, Duhig T, Wilson D, Taylor-Papadimitriou J, Gendler SJ (1990) Structure and expression of the human polymorphic epithelial mucin gene: an expressed VNTR unit. Biochem Biophys Res Commun 173:1019PubMedGoogle Scholar
  58. 58.
    Gendler SJ, Lancaster CA, Taylor-Papadimitriou J, Duhig T, Peat N, Burchell J, Pemberton L, Lalani EN, Wilson D (1990) Molecular cloning and expression of human tumor-associated polymorphic epithelial mucin. J Biol Chem 265:15286PubMedGoogle Scholar
  59. 59.
    Gendler SJ (2001) MUC1, the renaissance molecule. J Mammary Gland Biol Neoplasia 6:339CrossRefPubMedGoogle Scholar
  60. 60.
    DeSouza MM, Surveyor GA, Price RE, Julian J, Kardon R, Zhou X, Gendler S, Hilkens J, Carson DD (1999) MUC1/episialin: a critical barrier in the female reproductive tract. J Reprod Immunol 45:127PubMedGoogle Scholar
  61. 61.
    Agrawal B, Gendler SJ, Longenecker BM (1998) The biological role of mucins in cellular interactions and immune regulation: prospects for cancer immunotherapy. Mol Med Today 4:397CrossRefPubMedGoogle Scholar
  62. 62.
    Agrawal B, Krantz MJ, Parker J, Longenecker BM (1998) Expression of MUC1 mucin on activated human T cells: implications for a role of MUC1 in normal immune regulation. Cancer Res 58:4079PubMedGoogle Scholar
  63. 63.
    Hayes DF, Zurawski VR Jr, Kufe DW (1986) Comparison of circulating CA15–3 and carcinoembryonic antigen levels in patients with breast cancer. J Clin Oncol 4:1542PubMedGoogle Scholar
  64. 64.
    Muller S, Alving K, Peter-Katalinic J, Zachara N, Gooley AA, Hanisch FG (1999) High density O-glycosylation on tandem repeat peptide from secretory MUC1 of T47D breast cancer cells. J Biol Chem 274:18165CrossRefPubMedGoogle Scholar
  65. 65.
    Muller S, Hanisch FG (2002) Recombinant MUC1 probe authentically reflects cell-specific O-glycosylation profiles of endogenous breast cancer mucin. High density and prevalent core 2-based glycosylation. J Biol Chem 277:26103CrossRefPubMedGoogle Scholar
  66. 66.
    Hiltbold EM, Alter MD, Ciborowski P, Finn OJ (1999) Presentation of MUC1 tumor antigen by class I MHC and CTL function correlate with the glycosylation state of the protein taken Up by dendritic cells. Cell Immunol 194:143CrossRefPubMedGoogle Scholar
  67. 67.
    Paul WE (1999) Fundamental immunology. Lippincott-Raven, PhiladelphiaGoogle Scholar
  68. 68.
    von Mensdorff-Pouilly S, Verstraeten AA, Kenemans P, Snijdewint FG, Kok A, Van Kamp GJ, Paul MA, Van Diest PJ, Meijer S, Hilgers J (2000) Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin. J Clin Oncol 18:574PubMedGoogle Scholar
  69. 69.
    von Mensdorff-Pouilly S, Gourevitch MM, Kenemans P, Verstraeten AA, van Kamp GJ, Kok A, van Uffelen K, Snijdewint FG, Paul MA, Meijer S, Hilgers J (1998) An enzyme-linked immunosorbent assay for the measurement of circulating antibodies to polymorphic epithelial mucin (MUC1). Tumour Biol 19:186CrossRefPubMedGoogle Scholar
  70. 70.
    Croce MV, Isla-Larrain MT, Capafons A, Price MR, Segal-Eiras A (2001) Humoral immune response induced by the protein core of MUC1 mucin in pregnant and healthy women. Breast Cancer Res Treat 69:1CrossRefPubMedGoogle Scholar
  71. 71.
    Croce MV, Isla-Larrain MT, Price MR, Segal-Eiras A (2001) Detection of circulating mammary mucin (Muc1) and MUC1 immune complexes (Muc1-CIC) in healthy women. Int J Biol Markers 16:112PubMedGoogle Scholar
  72. 72.
    Price MR, Clarke AJ, Robertson JF, O'Sullivan C, Baldwin RW, Blamey RW (1990) Detection of polymorphic epithelial mucins in the serum of systemic breast cancer patients using the monoclonal antibody, NCRC-11. Cancer Immunol Immunother 31:269PubMedGoogle Scholar
  73. 73.
    Gilewski T, Adluri S, Ragupathi G, Zhang S, Yao TJ, Panageas K, Moynahan M, Houghton A, Norton L, Livingston PO (2000) Vaccination of high-risk breast cancer patients with mucin-1 (MUC1) keyhole limpet hemocyanin conjugate plus QS-21. Clin Cancer Res 6:1693Google Scholar
  74. 74.
    MacLean GD, Reddish MA, Koganty RR, Longenecker BM (1996) Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. J Immunother Emphasis Tumor Immunol 19:59PubMedGoogle Scholar
  75. 75.
    Lloyd KO (1991) Humoral immune responses to tumor-associated carbohydrate antigens. Semin Cancer Biol 2:421PubMedGoogle Scholar
  76. 76.
    Coomber DW, Hawkins NJ, Dalley D, Ward RL (1998) The significance of anti-sialyl-Tn antibodies in patients with colorectal and breast cancer. Neoplasma 45:12PubMedGoogle Scholar
  77. 77.
    Mitchell MS (2002) Cancer vaccines, a critical review--part II. Curr Opin Investig Drugs 3:150CrossRefPubMedGoogle Scholar
  78. 78.
    MacLean GD, Miles DW, Rubens RD, Reddish MA, Longenecker BM (1996) Enhancing the effect of THERATOPE STn-KLH cancer vaccine in patients with metastatic breast cancer by pretreatment with low-dose intravenous cyclophosphamide. J Immunother Emphasis Tumor Immunol 19:309PubMedGoogle Scholar
  79. 79.
    Holmberg LA, Oparin DV, Gooley T, Lilleby K, Bensinger W, Reddish MA, MacLean GD, Longenecker BM, Sandmaier BM (2000) Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE STn-KLH cancer vaccine. Bone Marrow Transplant 25:1233CrossRefPubMedGoogle Scholar
  80. 80.
    Thornthwaite JT (2000) Anti-malignin antibody in serum and other tumor marker determinations in breast cancer. Cancer Lett 148:39CrossRefPubMedGoogle Scholar
  81. 81.
    Abrams MB, Bednarek KT, Bogoch S, Bogoch ES, Dardik HJ, Dowden R, Fox SC, Goins EE, Goodfried G, Herrman RA et al (1994) Early detection and monitoring of cancer with the anti-malignin antibody test. Cancer Detect Prev 18:65PubMedGoogle Scholar
  82. 82.
    Crawford LV, Pim DC, Bulbrook RD (1982) Detection of antibodies against the cellular protein p53 in sera from patients with breast cancer. Int J Cancer 30:403PubMedGoogle Scholar
  83. 83.
    Metcalfe S, Wheeler TK, Picken S, Negus S, Jo Milner A (2000) P53 autoantibodies in 1006 patients followed up for breast cancer. Breast Cancer Res 2:438CrossRefPubMedGoogle Scholar
  84. 84.
    Schlichtholz B, Legros Y, Gillet D, Gaillard C, Marty M, Lane D, Calvo F, Soussi T (1992) The immune response to p53 in breast cancer patients is directed against immunodominant epitopes unrelated to the mutational hot spot. Cancer Res 52:6380PubMedGoogle Scholar
  85. 85.
    Angelopoulou K, Yu H, Bharaj B, Giai M, Diamandis EP (2000) p53 gene mutation, tumor p53 protein overexpression, and serum p53 autoantibody generation in patients with breast cancer. Clin Biochem 33:53CrossRefPubMedGoogle Scholar
  86. 86.
    Davidoff AM, Iglehart JD, Marks JR (1992) Immune response to p53 is dependent upon p53/HSP70 complexes in breast cancers. Proc Natl Acad Sci U S A 89:3439PubMedGoogle Scholar
  87. 87.
    Manjili MH, Wang XY, Park J, Facciponte JG, Repasky EA, Subjeck JR (2002) Immunotherapy of cancer using heat shock proteins. Front Biosci 7: d43PubMedGoogle Scholar
  88. 88.
    Conroy SE, Sasieni PD, Fentiman I, Latchman DS (1998) Autoantibodies to the 90 kDa heat shock protein and poor survival in breast cancer patients. Eur J Cancer 34:942PubMedGoogle Scholar
  89. 89.
    Conroy SE, Sasieni PD, Amin V, Wang DY, Smith P, Fentiman IS, Latchman DS (1998) Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer. Br J Cancer 77:1875PubMedGoogle Scholar
  90. 90.
    Yang NS, McGrath CM, Furmanski P (1978) Presence of a mouse mammary tumor virus-related antigen in human breast carcinoma cells and its absence from normal mammary epithelial cells. J Natl Cancer Inst 61:1205PubMedGoogle Scholar
  91. 91.
    Yang NS, Soule HD, McGrath CM (1977) Expression of murine mammary tumor virus-related antigens in human breast carcinoma (MCF-7) cells. J Natl Cancer Inst 59:1357PubMedGoogle Scholar
  92. 92.
    Wang Y, Holland JF, Bleiweiss IJ, Melana S, Liu X, Pelisson I, Cantarella A, Stellrecht K, Mani S, Pogo BG (1995) Detection of mammary tumor virus env gene-like sequences in human breast cancer. Cancer Res 55:5173PubMedGoogle Scholar
  93. 93.
    Malivanova TF, Kriukova IN, Litvinov SV, Ermilova VD, Shirin DF, Blokhina NG (1995) [Humoral antibodies to structural proteins of murine mammary tumor virus as a potential immunologic marker of human breast cancer]. Vopr Onkol 41:43PubMedGoogle Scholar
  94. 94.
    Zotter S, Grossmann H, Francois C, Kozma S, Hainaut P, Calberg-Bacq CM, Osterrieth PM (1983) Among the human antibodies reacting with intracytoplasmic a particles of mouse mammary tumor virus, some react with MMTV p14, the nucleic-acid-binding protein, and others with MMTV p28, the main core protein. Int J Cancer 32:27PubMedGoogle Scholar
  95. 95.
    Poon MC, Tomana M, Niedermeier W (1983) Serum antibodies against mouse mammary tumor-virus-associated antigen detected nine months before appearance of a breast carcinoma. Ann Intern Med 98:937PubMedGoogle Scholar
  96. 96.
    Bowen JM, Dmochowski L, Miller MF, Priori ES, Seman G, Dodson ML, Maruyama K (1976) Implications of humoral antibody in mice and humans to breast tumor and mouse mammary tumor virus-associated antigens. Cancer Res 36:759PubMedGoogle Scholar
  97. 97.
    Tomana M, Kajdos AH, Niedermeier W, Durkin WJ, Mestecky J (1981) Antibodies to mouse mammary tumor virus-related antigen in sera of patients with breast carcinoma. Cancer 47:2696PubMedGoogle Scholar
  98. 98.
    Levine PH, Mesa-Tejada R, Keydar I, Tabbane F, Spiegelman S, Mourali N (1984) Increased incidence of mouse mammary tumor virus-related antigen in Tunisian patients with breast cancer. Int J Cancer 33:305PubMedGoogle Scholar
  99. 99.
    Day NK, Witkin SS, Sarkar NH, Kinne D, Jussawalla DJ, Levin A, Hsia CC, Geller N, Good RA (1981) Antibodies reactive with murine mammary tumor virus in sera of patients with breast cancer: geographic and family studies. Proc Natl Acad Sci U S A 78:2483PubMedGoogle Scholar
  100. 100.
    Witkin SS, Egeli RA, Sarkar NH, Good RA, Day NK (1979) Virolysis of mouse mammary tumor virus by sera from breast cancer patients. Proc Natl Acad Sci U S A 76:2984PubMedGoogle Scholar
  101. 101.
    Dion AS, Girardi AJ, Williams CC, Pomenti AA, Redfield ES (1987) Responses of serum from breast cancer patients to murine mammary tumor virus: fact or artifact? J Natl Cancer Inst 79:207PubMedGoogle Scholar
  102. 102.
    Kovarik A, Hlubinova K, Prachar J, Simkovic D, Knotek J (1989) No significant correlation between specific antibodies to mouse mammary tumour virus and human cancer. Br J Cancer 60:572PubMedGoogle Scholar
  103. 103.
    Jager D, Stockert E, Gure AO, Scanlan MJ, Karbach J, Jager E, Knuth A, Old LJ, Chen YT (2001) Identification of a tissue-specific putative transcription factor in breast tissue by serological screening of a breast cancer library. Cancer Res 61:2055PubMedGoogle Scholar
  104. 104.
    Tomkiel JE, Alansari H, Tang N, Virgin JB, Yang X, VandeVord P, Karvonen RL, Granda JL, Kraut MJ, Ensley JF, Fernandez-Madrid F (2002) Autoimmunity to the M(r) 32,000 subunit of replication protein A in breast cancer. Clin Cancer Res 8:752PubMedGoogle Scholar
  105. 105.
    Garcia-Lozano R, Gonzalez-Escribano F, Sanchez-Roman J, Wichmann I, Nunez-Roldan A (1995) Presence of antibodies to different subunits of replication protein A in autoimmune sera. Proc Natl Acad Sci U S A 92:5116PubMedGoogle Scholar
  106. 106.
    Hansen MH, Ostenstad B, Sioud M (2001) Identification of immunogenic antigens using a phage-displayed cDNA library from an invasive ductal breast carcinoma tumour. Int J Oncol 19:1303PubMedGoogle Scholar
  107. 107.
    Sinnreich M, Assal F, Hefft S, Magistris MR, Chizzolini C, Landis T, Burkhard PR (2001) Anti-GAD antibodies and breast cancer in a patient with stiff-person syndrome: a puzzling association. Eur Neurol 46:51CrossRefPubMedGoogle Scholar
  108. 108.
    Di Paolo G, Sankaranarayanan S, Wenk MR, Daniell L, Perucco E, Caldarone BJ, Flavell R, Picciotto MR, Ryan TA, Cremona O, De Camilli P (2002) Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron 33:789PubMedGoogle Scholar
  109. 109.
    Floyd S, Butler MH, Cremona O, David C, Freyberg Z, Zhang X, Solimena M, Tokunaga A, Ishizu H, Tsutsui K, De Camilli P (1998) Expression of amphiphysin I, an autoantigen of paraneoplastic neurological syndromes, in breast cancer. Mol Med 4:29PubMedGoogle Scholar
  110. 110.
    David C, McPherson PS, Mundigl O, de Camilli P (1996) A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci U S A 93:331CrossRefPubMedGoogle Scholar
  111. 111.
    McPherson PS, Garcia EP, Slepnev VI, David C, Zhang X, Grabs D, Sossin WS, Bauerfeind R, Nemoto Y, De Camilli P (1996) A presynaptic inositol-5-phosphatase. Nature 379:353CrossRefPubMedGoogle Scholar
  112. 112.
    David C, Solimena M, De Camilli P (1994) Autoimmunity in stiff-Man syndrome with breast cancer is targeted to the C-terminal region of human amphiphysin, a protein similar to the yeast proteins, Rvs167 and Rvs161. FEBS Lett 351:73CrossRefPubMedGoogle Scholar
  113. 113.
    Berghs S, Ferracci F, Maksimova E, Gleason S, Leszczynski N, Butler M, De Camilli P, Solimena M (2001) Autoimmunity to beta IV spectrin in paraneoplastic lower motor neuron syndrome. Proc Natl Acad Sci U S A 98:6945CrossRefPubMedGoogle Scholar
  114. 114.
    Reeves WH (2001) Tumor immunity and autoimmunity: a case of Dr. Jekyll and Mr. Hyde. Clin Immunol 100:129CrossRefPubMedGoogle Scholar
  115. 115.
    Buckanovich RJ, Posner JB, Darnell RB (1993) Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system. Neuron 11:657PubMedGoogle Scholar
  116. 116.
    Aloisi F, Ambrosini E, Columba-Cabezas S, Magliozzi R, Serafini B (2001) Intracerebral regulation of immune responses. Ann Med 33:510PubMedGoogle Scholar
  117. 117.
    Wahid FS, Fun LC, Keng CS, Ismail F (2001) Breast carcinoma presenting as immune thrombocytopenic purpura. Int J Hematol 73:399PubMedGoogle Scholar
  118. 118.
    Saxman SB, Seitz D (1997) Breast cancer associated with palmar fasciitis and arthritis. J Clin Oncol 15:3515PubMedGoogle Scholar
  119. 119.
    Wenzel J (2002) Scleroderma and malignancy: mechanisms of interrelationship. Eur J Dermatol 12:296PubMedGoogle Scholar
  120. 120.
    Nadel E, Ackerman LV (1950) Lesions resembling Boeck's sarcoid in lymph nodes draining an area containing a malignant neoplasm. Am J Clin Pathol 20:952Google Scholar
  121. 121.
    Black M, Kerpe, S, and Speer, FD (1953) Lymph node structure in patients with cancer of the breast. Am J Pathol 29:505Google Scholar
  122. 122.
    Hirschl S, Black MM, Kwon CS (1976) Ultrastructural characteristics of sinus histiocytic reaction in lymph nodes draining various stages of breast cancer. Cancer 38:807PubMedGoogle Scholar
  123. 123.
    Sobrinho-Simoes MA, Brandao A, Sousa-Le F, Giesteira-Almeida A (1985) Prognostic significance of some pathologic factors in breast carcinoma. Pathol Res Pract 180:185PubMedGoogle Scholar
  124. 124.
    Syrjanen KJ, Hjelt LH (1978) Tumor-host interrelationships in carcinoma of the female breast. Surg Gynecol Obstet 147:43PubMedGoogle Scholar
  125. 125.
    Hunter RL, Ferguson DJ, Coppleson LW (1975) Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes. Cancer 36:528PubMedGoogle Scholar
  126. 126.
    Hartveit F (1980) Axillary node histology in cases of infiltrating breast cancer without nodal metastases dying later of disseminated disease. Invest Cell Pathol 3:311PubMedGoogle Scholar
  127. 127.
    Wernicke M, Podesta A (1984) Host defense factors, tumor aggressiveness, and prognosis associated with carcinomas of the breast. Hum Pathol 15:423PubMedGoogle Scholar
  128. 128.
    Black MM, Hankey BF, Aron JL, Prorok PC (1984) Possible immunological implications of an association between the stages of first and second independent breast cancers. Breast Cancer Res Treat 4:95PubMedGoogle Scholar
  129. 129.
    Fisher ER, Fisher B, Sass R, Wickerham L (1984) Pathologic findings from the National Surgical Adjuvant Breast Project (Protocol No. 4). XI. Bilateral breast cancer. Cancer 54:3002PubMedGoogle Scholar
  130. 130.
    Urdiales-Viedma M, Nogales-Fernandez F, Martos-Padilla S, Sanchez-Cantalejo E (1986) Correlation of histologic grade and lymph node status with some histopathologic discriminants in breast cancer. Tumori 72:43PubMedGoogle Scholar
  131. 131.
    Silverberg SG, Chitale AR, Hind AD, Frazier AB, Levitt SH (1970) Sinus histiocytosis and mammary carcinoma: study of 366 radical mastectomies and an historical review. Cancer 26:1177PubMedGoogle Scholar
  132. 132.
    Tsakraklides V, Olson P, Kersey JH, Good RA (1974) Prognostic significance of the regional lymph node histology in cancer of the breast. Cancer 34:1259PubMedGoogle Scholar
  133. 133.
    Whitford P, George WD, Campbell AM (1992) Flow cytometric analysis of tumour infiltrating lymphocyte activation and tumour cell MHC class I and II expression in breast cancer patients. Cancer Lett 61:157PubMedGoogle Scholar
  134. 134.
    Morton BA, Ramey WG, Paderon H, Miller RE (1986) Monoclonal antibody-defined phenotypes of regional lymph node and peripheral blood lymphocyte subpopulations in early breast cancer. Cancer Res 46:2121PubMedGoogle Scholar
  135. 135.
    Eremin O, Roberts P, Plumb D, Stephens JP (1980) Human regional tumour lymph nodes: alterations of micro-architecture and lymphocyte subpopulations. Br J Cancer 41:62PubMedGoogle Scholar
  136. 136.
    Wernicke M (1975) Quantitative morphologic assessment of immunoreactivity in regional lymph nodes of patients with carcinoma of the breast. Surg Gynecol Obstet 140:919PubMedGoogle Scholar
  137. 137.
    Goldstein NI, Nagle R, Villar H, Hersh E, Fisher PB (1990) Isolation and characterization of a human monoclonal antibody which reacts with breast and colorectal carcinoma. Anticancer Res 10:1491PubMedGoogle Scholar
  138. 138.
    Macey DJ, Grant EJ, Kasi L, Rosenblum MG, Zhang HZ, Katz RL, Rieger PT, LeBherz D, South M, Greiner JW, Schlom J, Podoloff DA, Murray JL (1997) Effect of recombinant alpha-interferon on pharmacokinetics, biodistribution, toxicity, and efficacy of 131I-labeled monoclonal antibody CC49 in breast cancer: a phase II trial. Clin Cancer Res 3:1547PubMedGoogle Scholar
  139. 139.
    Petrarca C, Casalino B, von Mensdorff-Pouilly S, Rughetti A, Rahimi H, Scambia G, Hilgers J, Frati L, Nuti M (1999) Isolation of MUC1-primed B lymphocytes from tumour-draining lymph nodes by immunomagnetic beads. Cancer Immunol Immunother 47:272CrossRefPubMedGoogle Scholar
  140. 140.
    Tamaki Y, Kobayashi T, Higashiyama M, Shimano T, Mori T, Murakami H (1989) A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient. Hybridoma 8:293PubMedGoogle Scholar
  141. 141.
    Kjeldsen TB, Rasmussen BB, Rose C, Zeuthen J (1988) Human-human hybridomas and human monoclonal antibodies obtained by fusion of lymph node lymphocytes from breast cancer patients. Cancer Res 48:3208PubMedGoogle Scholar
  142. 142.
    Walsh MD, Luckie SM, Cummings MC, Antalis TM, McGuckin MA (1999) Heterogeneity of MUC1 expression by human breast carcinoma cell lines in vivo and in vitro. Breast Cancer Res Treat 58:255CrossRefPubMedGoogle Scholar
  143. 143.
    Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF, Arteaga CL (2001) Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Cancer Res 61:8887PubMedGoogle Scholar
  144. 144.
    Cote RJ, Morrissey DM, Houghton AN, Thomson TM, Daly ME, Oettgen HF, Old LJ (1986) Specificity analysis of human monoclonal antibodies reactive with cell surface and intracellular antigens. Proc Natl Acad Sci U S A 83:2959PubMedGoogle Scholar
  145. 145.
    Cote RJ, Morrissey DM, Houghton AN, Beattie EJ Jr, Oettgen HF, Old LJ (1983) Generation of human monoclonal antibodies reactive with cellular antigens. Proc Natl Acad Sci U S A 80:2026PubMedGoogle Scholar
  146. 146.
    Teramoto YA, Meriani R, Wunderlich D, Schlom J (1982) The immunohistochemical reactivity of a human monoclonal antibody with tissue sections of human mammary tumors. Cancer 50:241PubMedGoogle Scholar
  147. 147.
    Schlom J, Wunderlich D, Teramoto YA (1980) Generation of human monoclonal antibodies reactive with human mammary carcinoma cells. Proc Natl Acad Sci U S A 77:6841PubMedGoogle Scholar
  148. 148.
    Wunderlich D, Teramoto YA, Alford C, Schlom J (1981) The use of lymphocytes from axillary lymph nodes of mastectomy patients to generate human monoclonal antibodies. Eur J Cancer Clin Oncol 17:719PubMedGoogle Scholar
  149. 149.
    Schlom J, Colcher D, Hand PH, Greiner J, Wunderlich D, Weeks M, Fisher PB, Noguchi P, Pestka S, Kufe D (1985) Monoclonal antibodies reactive with breast tumor-associated antigens. Adv Cancer Res 43:143PubMedGoogle Scholar
  150. 150.
    Imam A, Taylor CR (1989) Biochemical and immunological characterizations of antigens recognised by human monoclonal antibodies. Br J Cancer 59:922PubMedGoogle Scholar
  151. 151.
    Imam A, Drushella MM, Taylor CR, Tokes ZA (1985) Generation and immunohistological characterization of human monoclonal antibodies to mammary carcinoma cells. Cancer Res 45:263PubMedGoogle Scholar
  152. 152.
    Baba M, Kobayashi T, Tamaki Y, Mishima H, Yagyu T, Morimoto H, Monden T, Shimano T, Tsuji Y, Murakami H et al (1992) A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid. Hybridoma 11:107PubMedGoogle Scholar
  153. 153.
    Posner MR, Elboim HS, Tumber MB, Wiest PM, Tibbetts LM (1991) An IgG human monoclonal antibody reactive with a surface membrane antigen expressed on malignant breast cancer cells. Hum Antibodies Hybridomas 2:74PubMedGoogle Scholar
  154. 154.
    Punt CJ, Barbuto JA, Zhang H, Grimes WJ, Hatch KD, Hersh EM (1994) Anti-tumor antibody produced by human tumor-infiltrating and peripheral blood B lymphocytes. Cancer Immunol Immunother 38:225PubMedGoogle Scholar
  155. 155.
    Shimokawara I, Imamura M, Yamanaka N, Ishii Y, Kikuchi K (1982) Identification of lymphocyte subpopulations in human breast cancer tissue and its significance: an immunoperoxidase study with anti-human T- and B-cell sera. Cancer 49:1456PubMedGoogle Scholar
  156. 156.
    Lee AH, Happerfield LC, Bobrow LG, Millis RR (1997) Angiogenesis and inflammation in ductal carcinoma in situ of the breast. J Pathol 181:200CrossRefPubMedGoogle Scholar
  157. 157.
    Bilik R, Mor C, Hazaz B, Moroz C (1989) Characterization of T-lymphocyte subpopulations infiltrating primary breast cancer. Cancer Immunol Immunother 28:143PubMedGoogle Scholar
  158. 158.
    Chin Y, Janseens J, Vandepitte J, Vandenbrande J, Opdebeek L, Raus J (1992) Phenotypic analysis of tumor-infiltrating lymphocytes from human breast cancer. Anticancer Res 12:1463PubMedGoogle Scholar
  159. 159.
    Marsigliante S, Biscozzo L, Marra A, Nicolardi G, Leo G, Lobreglio GB, Storelli C (1999) Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer Lett 139:33PubMedGoogle Scholar
  160. 160.
    Grekou AN, Toliou T, Stravoravdi P, Patakiouta F, Tsoukalas T, Pinakidis M, Keramidas G (1996) Correlation of apoptosis with the distribution and composition of lymphocytic infiltrate in human breast carcinomas. Anticancer Res 16:3991PubMedGoogle Scholar
  161. 161.
    Wang BL, Springer GF, Kaufman MW (1996) Concurrent immunohistochemical staining of tumor-infiltrating lymphocytes and carcinoma-associated T (Thomsen-Friedenreich)/Tn antigens in human breast carcinoma. J Histochem Cytochem 44:187PubMedGoogle Scholar
  162. 162.
    Coronella JA, Telleman P, Kingsbury GA, Truong TD, Hays S, Junghans RP (2001) Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer. Cancer Res 61:7889PubMedGoogle Scholar
  163. 163.
    Kang YM, Zhang X, Wagner UG, Yang H, Beckenbaugh RD, Kurtin PJ, Goronzy JJ, Weyand CM (2002) CD8 T cells are required for the formation of ectopic germinal centers in rheumatoid synovitis. J Exp Med 195:1325CrossRefPubMedGoogle Scholar
  164. 164.
    Schroder AE, Greiner A, Seyfert C, Berek C (1996) Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis. Proc Natl Acad Sci U S A 93:221CrossRefPubMedGoogle Scholar
  165. 165.
    Takemura S, Braun A, Crowson C, Kurtin PJ, Cofield RH, O'Fallon WM, Goronzy JJ, Weyand CM (2001) Lymphoid neogenesis in rheumatoid synovitis. J Immunol 167:1072PubMedGoogle Scholar
  166. 166.
    Bell D, Chomarat P, Broyles D, Netto G, Harb GM, Lebecque S, Valladeau J, Davoust J, Palucka KA, Banchereau J (1999) In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 190:1417CrossRefPubMedGoogle Scholar
  167. 167.
    Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767PubMedGoogle Scholar
  168. 168.
    Tsuge T, Yamakawa M, Tsukamoto M (2000) Infiltrating dendritic/Langerhans cells in primary breast cancer. Breast Cancer Res Treat 59:141CrossRefPubMedGoogle Scholar
  169. 169.
    Katano M, Kubota E, Nagumo F, Matsuo T, Hisatsugu T, Tadano J (1994) Inhibition of tumor cell growth by a human B-cell line. Biotherapy 8:1PubMedGoogle Scholar
  170. 170.
    Barbas CF (2000) Phage display: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYGoogle Scholar
  171. 171.
    Coronella-Wood J, Maly M, Tatum L, Hersh EM (2002) Tumor specific antibodies from breast tumor infiltrating B cells. In: Abstracts for the 17th annual scientific meeting of the Society for Biological Therapy, La Jolla, CA, November 7-10, 2002. J Immunother 25(6):S1–S37CrossRefPubMedGoogle Scholar
  172. 172.
    Klein U, Kuppers R, Rajewsky K (1993) Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life. Eur J Immunol 23:3272PubMedGoogle Scholar
  173. 173.
    Yamada M, Wasserman R, Reichard BA, Shane S, Caton AJ, Rovera G (1991) Preferential utilization of specific immunoglobulin heavy chain diversity and joining segments in adult human peripheral blood B lymphocytes. J Exp Med 173:395PubMedGoogle Scholar
  174. 174.
    Wang X, Stollar BD (1999) Immunoglobulin VH gene expression in human aging [published erratum appears in Clin Immunol. 2000 Mar 94(3):219]. Clin Immunol 93:132CrossRefPubMedGoogle Scholar
  175. 175.
    Zanetti M, Capra JD (1995) The antibodies. Harwood Academic Publishers, LuxembourgGoogle Scholar
  176. 176.
    Lossos IS, Tibshirani R, Narasimhan B, Levy R (2000) The inference of antigen selection on Ig genes. J Immunol 165:5122PubMedGoogle Scholar
  177. 177.
    Carayannopoulos MO, Potter KN, Li Y, Natvig JB, Capra JD (2000) Evidence that human immunoglobulin M rheumatoid factors can be derived from the natural autoantibody pool and undergo an antigen driven immune response in which somatically mutated rheumatoid factors have lower affinities for immunoglobulin G Fc than their germline counterparts. Scand J Immunol 51:327PubMedGoogle Scholar
  178. 178.
    Itoh K, Meffre E, Albesiano E, Farber A, Dines D, Stein P, Asnis SE, Furie RA, Jain RI, Chiorazzi N (2000) Immunoglobulin heavy chain variable region gene replacement as a mechanism for receptor revision in rheumatoid arthritis synovial tissue B lymphocytes [In Process Citation]. J Exp Med 192:1151CrossRefPubMedGoogle Scholar
  179. 179.
    Itoh K, Patki V, Furie RA, Chartash EK, Jain RI, Lane L, Asnis SE, Chiorazzi N (1999) Clonal expansion is a characteristic feature of the B-cell repertoire of patients with rheumatoid arthritis. Arthritis Res 2:50CrossRefPubMedGoogle Scholar
  180. 180.
    de Boer BA, Voigt I, Kim HJ, Camacho SA, Lipp M, Forster R, Berek C (2000) Affinity maturation in ectopic germinal centers. Curr Top Microbiol Immunol 251:191PubMedGoogle Scholar
  181. 181.
    Menard S, Casalini P, Tomasic G, Pilotti S, Cascinelli N, Bufalino R, Perrone F, Longhi C, Rilke F, Colnaghi MI (1999) Pathobiologic identification of two distinct breast carcinoma subsets with diverging clinical behaviors. Breast Cancer Res Treat 55:169PubMedGoogle Scholar
  182. 182.
    Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, Salvadori B, Colnaghi MI, Rilke F (1997) Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res 3:817PubMedGoogle Scholar
  183. 183.
    Pupa SM, Bufalino R, Invernizzi AM, Andreola S, Rilke F, Lombardi L, Colnaghi MI, Menard S (1996) Macrophage infiltrate and prognosis in c-erbB-2-overexpressing breast carcinomas [see comments]. J Clin Oncol 14:85PubMedGoogle Scholar
  184. 184.
    Barbera-Guillem E, Nyhus JK, Wolford CC, Friece CR, Sampsel JW (2002) Vascular endothelial growth factor secretion by tumor-infiltrating macrophages essentially supports tumor angiogenesis, and IgG immune complexes potentiate the process. Cancer Res 62:7042PubMedGoogle Scholar
  185. 185.
    Nelson MB, Nyhus JK, Oravecz-Wilson KI, Barbera-Guillem E (2001) Tumor cells express FcgammaRI which contributes to tumor cell growth and a metastatic phenotype. Neoplasia 3:115CrossRefPubMedGoogle Scholar
  186. 186.
    Quan N, Zhang Z, Demetrikopoulos MK, Kitson RP, Chambers WH, Goldfarb RH, Weiss JM (1999) Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat. Cancer Res 59:1080PubMedGoogle Scholar
  187. 187.
    Harris JR (2000) Diseases of the breast. Lippicott Williams and Wilkins, PhiladelphiaGoogle Scholar
  188. 188.
    Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V (1977) Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up. Cancer 40:1365PubMedGoogle Scholar
  189. 189.
    Bloom HJ, Richardson WW, Field JR (1970) Host resistance and survival in carcinoma of breast: a study of 104 cases of medullary carcinoma in a series of 1,411 cases of breast cancer followed for 20 years. Br Med J 3:181PubMedGoogle Scholar
  190. 190.
    Pedersen L, Zedeler K, Holck S, Schiodt T, Mouridsen HT (1991) Medullary carcinoma of the breast, proposal for a new simplified histopathological definition. Based on prognostic observations and observations on inter- and intraobserver variability of 11 histopathological characteristics in 131 breast carcinomas with medullary features. Br J Cancer 63:591PubMedGoogle Scholar
  191. 191.
    Gaffey MJ, Frierson HF Jr, Mills SE, Boyd JC, Zarbo RJ, Simpson JF, Gross LK, Weiss LM (1993) Medullary carcinoma of the breast. Identification of lymphocyte subpopulations and their significance. Mod Pathol 6:721PubMedGoogle Scholar
  192. 192.
    Sienski W (1980) Immunohistological patterns of immunoglobulins in dysplasias, benign neoplasms and carcinomas of the breast. Tumori 66:699PubMedGoogle Scholar
  193. 193.
    Jensen V, Jensen ML, Kiaer H, Andersen J, Melsen F (1997) MIB-1 expression in breast carcinomas with medullary features: an immunohistological study including correlations with p53 and bcl-2. Virchows Arch 431:125CrossRefPubMedGoogle Scholar
  194. 194.
    Lazzaro B, Anderson AE, Kajdacsy-Balla A, Hessner MJ (2001) Antigenic characterization of medullary carcinoma of the breast: HLA-DR expression in lymph node positive cases. Appl Immunohistochem Mol Morphol 9:234CrossRefPubMedGoogle Scholar
  195. 195.
    Bacus SS, Zelnick CR, Chin DM, Yarden Y, Kaminsky DB, Bennington J, Wen D, Marcus JN, Page DL (1994) Medullary carcinoma is associated with expression of intercellular adhesion molecule-1: implication to its morphology and its clinical behavior. Am J Pathol 145:1337PubMedGoogle Scholar
  196. 196.
    Brown DM, Fisher TL, Wei C, Frelinger JG, Lord EM (2001) Tumours can act as adjuvants for humoral immunity. Immunology 102:486CrossRefPubMedGoogle Scholar
  197. 197.
    Demaria S, Volm MD, Shapiro RL, Yee HT, Oratz R, Formenti SC, Muggia F, Symmans WF (2001) Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res 7:3025PubMedGoogle Scholar
  198. 198.
    Prasad SC, Soldatenkov V, Notario V, Smulson M, Dritschilo A (1999) Detection of heterogeneity of apoptotic fragments of poly (ADP-ribose) polymerase in MDA-MB-468 breast cancer cells: two-dimensional gel analysis. Electrophoresis 20:618CrossRefPubMedGoogle Scholar
  199. 199.
    Gerner C, Frohwein U, Gotzmann J, Bayer E, Gelbmann D, Bursch W, Schulte-Hermann R (2000) The Fas-induced apoptosis analyzed by high throughput proteome analysis. J Biol Chem 275:39018CrossRefPubMedGoogle Scholar
  200. 200.
    Nouri-Shirazi M, Banchereau J, Bell D, Burkeholder S, Kraus ET, Davoust J, Palucka KA (2000) Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses. J Immunol 165:3797PubMedGoogle Scholar
  201. 201.
    Pietra G, Mortarini R, Parmiani G, Anichini A (2001) Phases of apoptosis of melanoma cells, but not of normal melanocytes, differently affect maturation of myeloid dendritic cells. Cancer Res 61:8218PubMedGoogle Scholar
  202. 202.
    Summers KL, Hock BD, McKenzie JL, Hart DN (2001) Phenotypic characterization of five dendritic cell subsets in human tonsils. Am J Pathol 159:285PubMedGoogle Scholar
  203. 203.
    Behr TM, Behe M, Wormann B (2001) Trastuzumab and breast cancer. N Engl J Med 345:995CrossRefPubMedGoogle Scholar
  204. 204.
    Zhang JY, Casiano CA, Peng XX, Koziol JA, Chan EK, Tan EM (2003) Enhancement of antibody detection in cancer using panel of recombinant tumor-associated antigens. Cancer Epidemiol Biomarkers Prev 12:136PubMedGoogle Scholar
  205. 205.
    Faig OZ, Lutz CS (2003) Novel specificity of anti-U1A autoimmune patient sera. Scand J Immunol 57:79CrossRefPubMedGoogle Scholar
  206. 206.
    Hermann P, Van-Kooten C, Gaillard C, Banchereau J, Blanchard D (1995) CD40 ligand-positive CD8+ T cell clones allow B cell growth and differentiation. Eur J Immunol 25:2972PubMedGoogle Scholar
  207. 207.
    Thomas E, Brewster DH, Black RJ, Macfarlane GJ (2000) Risk of malignancy among patients with rheumatic conditions. Int J Cancer 88:497CrossRefPubMedGoogle Scholar
  208. 208.
    Farsad K, Ringstad N, Takei K, Floyd SR, Rose K, De Camilli P (2001) Generation of high curvature membranes mediated by direct endophilin bilayer interactions. J Cell Biol 155:193CrossRefPubMedGoogle Scholar
  209. 209.
    Brooks S, Takita H, Shin K, Sharma S, Fang Y, Karakousis C (2002) Treatment of cancer by direct intra-tumor injection of granulocyte/monocyte-colony stimulating factor. J Immunother 25:S1CrossRefPubMedGoogle Scholar
  210. 210.
    Wang J, Foster A, Chin R, Yu P, Sun Y, Wang Y, Pfeffer K, Fu YX (2002) The complementation of lymphotoxin deficiency with LIGHT, a newly discovered TNF family member, for the restoration of secondary lymphoid structure and function. Eur J Immunol 32:1969CrossRefPubMedGoogle Scholar
  211. 211.
    Fu YX, Molina H, Matsumoto M, Huang G, Min J, Chaplin DD (1997) Lymphotoxin-alpha (LTalpha) supports development of splenic follicular structure that is required for IgG responses. J Exp Med 185:2111CrossRefPubMedGoogle Scholar
  212. 212.
    Bowman EP, Campbell JJ, Soler D, Dong Z, Manlongat N, Picarella D, Hardy RR, Butcher EC (2000) Developmental switches in chemokine response profiles during B cell differentiation and maturation. J Exp Med 191:1303CrossRefPubMedGoogle Scholar
  213. 213.
    Vanderlugt CL, Miller SD (2002) Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2:85CrossRefPubMedGoogle Scholar
  214. 214.
    Dhodapkar KM, Krasovsky J, Williamson B, Dhodapkar MV (2002) Antitumor monoclonal antibodies enhance cross-presentation ofcCellular antigens and the generation of myeloma-specific killer T cells by dendritic cells. J Exp Med 195:125CrossRefPubMedGoogle Scholar
  215. 215.
    Selenko N, Majdic O, Jager U, Sillaber C, Stockl J, Knapp W (2002) Cross-priming of cytotoxic T cells promoted by apoptosis-inducing tumor cell reactive antibodies? J Clin Immunol 22:124CrossRefPubMedGoogle Scholar
  216. 216.
    Cruz JS, Lau SY, Ramirez EM, Giovanni CD, Forni G, Morrison SL, Penichet ML (2003) Protein vaccination with the HER2/neu extracellular domain plus anti-HER2/neu antibody-cytokine fusion proteins induces a protective anti-HER2/neu immune response in mice. Vaccine 21:1317CrossRefPubMedGoogle Scholar
  217. 217.
    Reed VL, Mack DO, Smith LD (1987) Adenylosuccinate lyase as an indicator of breast and prostate malignancies: a preliminary report. Clin Biochem 20:349PubMedGoogle Scholar
  218. 218.
    Striekland DK, Ashcom JD, Williams S, Battey F, Behre E, McTigue K, Battey JF, Argraves WS (1991) Primary structure of alpha 2-macroglobulin receptor-associated protein: human homologue of a Heymann nephritis antigen. J Biol Chem 266:13364PubMedGoogle Scholar
  219. 219.
    Bieche I, Nogues C, Lidereau R (1999) Overexpression of BRCA2 gene in sporadic breast tumours. Oncogene 18:5232CrossRefPubMedGoogle Scholar
  220. 220.
    Bertwistle D, Swift S, Marston NJ, Jackson LE, Crossland S, Crompton MR, Marshall CJ, Ashworth A (1997) Nuclear location and cell cycle regulation of the BRCA2 protein. Cancer Res 57:5485PubMedGoogle Scholar
  221. 221.
    Santamaria I, Velasco G, Cazorla M, Fueyo A, Campo E, Lopez-Otin C (1998) Cathepsin L2, a novel human cysteine proteinase produced by breast and colorectal carcinomas. Cancer Res 58:1624PubMedGoogle Scholar
  222. 222.
    Sauer G, Kurzeder C, Grundmann R, Kreienberg R, Zeillinger R, Deissler H (2003) Expression of tetraspanin adaptor proteins below defined threshold values is associated with in vitro invasiveness of mammary carcinoma cells. Oncol Rep 10:405PubMedGoogle Scholar
  223. 223.
    Landberg G, Erlanson M, Roos G, Tan EM, Casiano CA (1996) Nuclear autoantigen p330d/CENP-F: a marker for cell proliferation in human malignancies. Cytometry 25:90CrossRefPubMedGoogle Scholar
  224. 224.
    Hussein D, Taylor SS (2002) Farnesylation of Cenp-F is required for G2/M progression and degradation after mitosis. J Cell Sci 115:3403PubMedGoogle Scholar
  225. 225.
    Zhang JY, Zhu W, Imai H, Kiyosawa K, Chan EK, Tan EM (2001) De-novo humoral immune responses to cancer-associated autoantigens during transition from chronic liver disease to hepatocellular carcinoma. Clin Exp Immunol 125:3CrossRefPubMedGoogle Scholar
  226. 226.
    Sorokine I, Ben-Mahrez K, Bracone A, Thierry D, Ishii S, Imamoto F, Kohiyama M (1991) Presence of circulating anti-c-myb oncogene product antibodies in human sera. Int J Cancer 47:665PubMedGoogle Scholar
  227. 227.
    Ben-Mahrez K, Sorokine I, Thierry D, Kawasumi T, Ishii S, Salmon R, Kohiyama M (1990) Circulating antibodies against c-myc oncogene product in sera of colorectal cancer patients. Int J Cancer 46:35PubMedGoogle Scholar
  228. 228.
    Deming SL, Nass SJ, Dickson RB, Trock BJ (2000) C-myc amplification in breast cancer: a meta-analysis of its occurrence and prognostic relevance. Br J Cancer 83:1688CrossRefPubMedGoogle Scholar
  229. 229.
    Yuan J, Eckerdt F, Bereiter-Hahn J, Kurunci-Csacsko E, Kaufmann M, Strebhardt K (2002) Cooperative phosphorylation including the activity of polo-like kinase 1 regulates the subcellular localization of cyclin B1. Oncogene 21:8282CrossRefPubMedGoogle Scholar
  230. 230.
    Yang DC, Wang F, Elliott RL, Head JF (2001) Expression of transferrin receptor and ferritin H-chain mRNA are associated with clinical and histopathological prognostic indicators in breast cancer. Anticancer Res 21:541PubMedGoogle Scholar
  231. 231.
    Pasquinelli R, Barba P, Capasso I, D'Aiuto M, D'Aiuto G, Anzisi AM, De Berardinis P, Guardiola J (1999) Circulating antibodies against the breast tumor marker GCDFP-15/gp17 in mammary carcinoma patients and in patients carrying benign breast conditions. Int J Cancer 84:568CrossRefPubMedGoogle Scholar
  232. 232.
    Mazurkiewicz M, Opolski A, Wietrzyk J, Radzikowski C, Kleinrok Z (1999) GABA level and GAD activity in human and mouse normal and neoplastic mammary gland. J Exp Clin Cancer Res 18:247PubMedGoogle Scholar
  233. 233.
    Nielsen FC, Nielsen J, Christiansen J (2001) A family of IGF-II mRNA binding proteins (IMP) involved in RNA trafficking. Scand J Clin Lab Invest Suppl:93CrossRefGoogle Scholar
  234. 234.
    Grabowski P, Kuhnel T, Muhr-Wilkenshoff F, Heine B, Stein H, Hopfner M, Germer CT, Scherubl H (2003) Prognostic value of nuclear survivin expression in oesophageal squamous cell carcinoma. Br J Cancer 88:115CrossRefPubMedGoogle Scholar
  235. 235.
    Hajitou A, Calberg-Bacq CM (1995) Fibroblast growth factor 3 is tumorigenic for mouse mammary cells orthotopically implanted in nude mice. Int J Cancer 63:702PubMedGoogle Scholar
  236. 236.
    Nupponen NN, Isola J, Visakorpi T (2000) Mapping the amplification of EIF3S3 in breast and prostate cancer. Genes Chromosomes Cancer 28:203CrossRefPubMedGoogle Scholar
  237. 237.
    Otto IM, Raabe T, Rennefahrt UE, Bork P, Rapp UR, Kerkhoff E (2000) The p150-Spir protein provides a link between c-Jun N-terminal kinase function and actin reorganization. Curr Biol 10:345CrossRefPubMedGoogle Scholar
  238. 238.
    Cao J, Gao T, Giuliano AE, Irie RF (1999) Recognition of an epitope of a breast cancer antigen by human antibody. Breast Cancer Res Treat 53:279CrossRefPubMedGoogle Scholar
  239. 239.
    Gao S, Witte MM, Scott RE (2002) P2P-R protein localizes to the nucleolus of interphase cells and the periphery of chromosomes in mitotic cells which show maximum P2P-R immunoreactivity. J Cell Physiol 191:145CrossRefPubMedGoogle Scholar
  240. 240.
    Le Naour F, Misek DE, Krause MC, Deneux L, Giordano TJ, Scholl S, Hanash SM (2001) Proteomics-based identification of RS/DJ-1 as a novel circulating tumor antigen in breast cancer. Clin Cancer Res 7:3328PubMedGoogle Scholar
  241. 241.
    de Bruijn DR, dos Santos NR, Kater-Baats E, Thijssen J, van den Berk L, Stap J, Balemans M, Schepens M, Merkx G, van Kessel AG (2002) The cancer-related protein SSX2 interacts with the human homologue of a Ras-like GTPase interactor, RAB3IP, and a novel nuclear protein, SSX2IP. Genes Chromosomes Cancer 34:285CrossRefPubMedGoogle Scholar
  242. 242.
    Lecomte F, Szpirer J, Szpirer C (1997) The S3a ribosomal protein gene is identical to the Fte-1 (v-fos transformation effector) gene and the TNF-alpha-induced TU-11 gene, and its transcript level is altered in transformed and tumor cells. Gene 186:271CrossRefPubMedGoogle Scholar
  243. 243.
    Shoenfeld Y, Hizi A, Tal R, Smorodinsky NI, Lavie G, Mor C, Schteren S, Mammon Z, Pinkhas J, Keydar T (1987) Human monoclonal antibodies derived from lymph nodes of a patient with breast carcinoma react with MuMTV polypeptides. Cancer 59:43PubMedGoogle Scholar
  244. 244.
    Aihara K, Yamada K, Murakami H, Nomura Y, Omura H (1988) Production of human-human hybridomas secreting monoclonal antibodies reactive to breast cancer cell lines. In Vitro Cell Dev Biol 24:959PubMedGoogle Scholar
  245. 245.
    Skaletsky E, Oh E, Rulot C, Baird SM, Burnett KG, Masuho Y, Astarita RW, Haghighi P, Wolf P, Collins H et al (1988) A human monoclonal antibody to cytokeratin intermediate filament antigens derived from a tumor draining lymph node. Hybridoma 7:367PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Arizona Cancer CenterUniversity of ArizonaTucsonUSA

Personalised recommendations