Skip to main content
SpringerLink
Log in

Role of the Immune System in Cancer Development and Therapeutic Implications

  • Chapter
The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies

Part of the book series: Medical Radiology ((Med Radiol Radiat Oncol))

  • 1219 Accesses

Abstract

This chapter elucidates immunological aspects in cancer therapy. For many years, the impact of the immune system in cancer immunity was a matter of debate. Nowadays, it is generally accepted that an active immune system can monitor, edit, and destroy malignantly transformed cells in vitro and in established tumor mouse models. However, the capacity of the immune system to fight human tumors is limited, as human tumors are highly individual, complex, and dynamic systems that have the capacity to modulate anticancer immune responses and to affect the tumor microenvironment. Here, we describe the development of innovative immunological strategies from a preclinical stage to clinical application. In the last decade, especially humanized monoclonal antibodies (mAb) have emerged as promising pharmaceutical tools (“magic bullet”) for the treatment of cancer in combination with radio- and/or chemotherapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adams C, Totpal K, Lawrence D, Marsters S, Pitti R, Yee S, Ross S, Deforge L, Koeppen H, Sagolla M, Compaan D, Lowman H, Hymowitz S, Ashkenazi A (2008) Structural and functional analysis of the interaction between the agonistic monoclonal antibody Apomab and the proapoptotic receptor DR5. Cell Death Differ 15:751–761

    Article  PubMed  CAS  Google Scholar 

  • Allan NC, Richards SM, Shepherd PC (1995) UK Medical Research Council randomized, multicenter trial of interferon alfa n1 for chronic myeloid leukaemia: improved survival irrespective of cytogenetic response. Lancet 345:1392–1397

    Article  PubMed  CAS  Google Scholar 

  • Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman DR, Palmer DC, Chan CC, Klebanoff CA, Overwijk WW, Rosenberg SA, Restifo NP (2005) CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol 174:2591–2601

    PubMed  CAS  Google Scholar 

  • Asea A, Stein-Streilein J (1998) Signalling through NK1.1 triggers NK cells to die but induces NK T cells to produce interleukin-4. Immunology 93:296–305

    Article  PubMed  CAS  Google Scholar 

  • Ashley DM, Faiola B, Nair S, Hale LP, Bigner DD, Gilboa E (1997) Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J Exp Med 186:1177–1182

    Article  PubMed  CAS  Google Scholar 

  • Atzpodien J, Schmitt E, Gertenbach U, Fornara P, Heynemann H, Maskow A et al., German Cooperative Renal Carcinoma Chemo-Immunotherapy Trials Group (DGCIN) (2005) Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumor nephrectomy: results of a prospectively randomized trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer 92:843–846

    Article  PubMed  CAS  Google Scholar 

  • Bajetta E, Di Leo A, Zampino MG, Sertoli MR, Comella G, Bardugni M et al (1994) Multicenter randomized trial of dacarbazine alone or in combination with two different doses and schedules of interferon alfa-2a in the treatment of advanced melanoma. J Clin Oncol 12:806–811

    PubMed  CAS  Google Scholar 

  • Banchereau J, Steinman RM (1998) Dendritic cells and the control of immunity. Nature 392:245–252

    Article  PubMed  CAS  Google Scholar 

  • Baselga J, Albanell J, Molina MA, Arribas J (2001) Mechanism of action of trastuzumab and scientific update. Semin Oncol 28:4–11

    Article  PubMed  CAS  Google Scholar 

  • Beechey RT, Edwards BE, Kelland CH (1986) Adenocarcinoma of the colon: an unusual case. Med J Aust 144:211–213

    PubMed  CAS  Google Scholar 

  • Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, Ove R, Kies MS, Baselga J, Youssoufian H, Amellal N, Rowinsky EK, Ang KK (2006) Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med 354:567–578

    Article  PubMed  CAS  Google Scholar 

  • Bontkes HJ, de Gruijl TD, van den Muysenberg AJ, Verheijen RH, Stukart MJ, Meijer CJ, Scheper RJ, Stacey SN, Duggan-Keen MF, Stern PL, Man S, Borysiewicz LK, Walboomers JM (2000) Human papillomavirus type 16 E6/E7-specific cytotoxic T lymphocytes in women with cervical neoplasia. Int J Cancer 88:92–98

    Article  PubMed  CAS  Google Scholar 

  • Boon T, van der Bruggen BP (1996) Human tumor antigens recognized by T lymphocytes. J Exp Med 183:725–729

    Article  PubMed  CAS  Google Scholar 

  • Boon T, Coulie PG, van den Eynde B (1997) Tumor antigens recognized by T cells. Immunol Today 18:267–268

    Article  PubMed  CAS  Google Scholar 

  • Boshoff C, Weiss R (2002) AIDS-related malignancies. Nat Rev Cancer 2:373–382

    Article  PubMed  CAS  Google Scholar 

  • Brandau S, Riemensberger J, Jacobsen M, Kemp D, Zhao W, Zhao X, Jocham D, Ratliff TL, Bohle A (2001) NK cells are essential for effective BCG immunotherapy. Int J Cancer 92:697–702

    Article  PubMed  CAS  Google Scholar 

  • Brichard V, Van Pel A, Wolfel T, Wolfel C, De Plaen E, Lethe B, Coulie P, Boon T (1993) The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 178:489–495

    Article  PubMed  CAS  Google Scholar 

  • Bronte V, Zanovello P (2005) Regulation of immune responses by l-arginine metabolism. Nat Rev Immunol 5:641–654

    Article  PubMed  CAS  Google Scholar 

  • Cameron DA, Cornbleet MC, MacKie RM, Hunter JA, Gore M, Hancock B, Smyth JF. (2001) Adjuvant interferon alpha 2b in high risk melanoma—the Scottish study. Br J Cancer 84:1146–1149

    Article  PubMed  CAS  Google Scholar 

  • Cheever MA, Disis ML, Bernhard H, Gralow JR, Hand SL, Huseby ES, Qin HL, Takahashi M, Chen W (1995) Immunity to oncogenic proteins. Immunol Rev 145:33–59

    Article  PubMed  CAS  Google Scholar 

  • Chen YT, Scanlan MJ, Sahin U, Tureci O, Gure AO, Tsang S, Williamson B, Stockert E, Pfreundschuh M, Old LJ (1997) A testicular antigen aberrantly expressed in human cancers detected by autologous antibody screening. Proc Natl Acad Sci USA 94:1914–1918

    Article  PubMed  CAS  Google Scholar 

  • Clark JI, Atkins MB, Urba WJ, Creech S, Figlin RA, Dutcher JP et al (2003) Adjuvant high-dose bolus interleukin-2 for patients with high risk renal cell carcinoma: a cytokine working group randomized trial. J Clin Oncol 21:3133–3140

    Article  PubMed  CAS  Google Scholar 

  • Coley WB (1893) II. Hawkins on tubercular peritonitis. Ann Surg 17:462–464

    Article  PubMed  CAS  Google Scholar 

  • Colomer R (2005) What is the best schedule for administration of gemcitabine-taxane? Cancer Treat Rev 31:S23–S28

    Article  PubMed  CAS  Google Scholar 

  • Contassot E, Gaide O, French LE (2007) Death receptors and apoptosis. Dermatol Clin 25:487–501, vii

    PubMed  CAS  Google Scholar 

  • Coulie PG, Brichard V, Van Pel A, Wolfel T, Schneider J, Traversari C, Mattei S, De Plaen E, Lurquin C, Szikora JP, Renauld JC, Boon T (1994) A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas. J Exp Med 180:35–42

    Article  PubMed  CAS  Google Scholar 

  • Coulie PG, Ikeda H, Baurain JF, Chiari R (1999) Antitumor immunity at work in a melanoma patient. Adv Cancer Res 76:213–242

    Article  PubMed  CAS  Google Scholar 

  • Degli-Esposti MA, Smyth MJ (2005) Close encounters of different kinds: dendritic cells and NK cells take centre stage. Nat Rev Immunol 5:112–124

    Article  PubMed  CAS  Google Scholar 

  • Dillman RO, Church C, Barth NM, Oldham RK, Wiemann MC (1997) Long-term survival after continuous infusion interleukin-2; Cancer Biother Radiopharm 12:243–248

    PubMed  CAS  Google Scholar 

  • Dudley ME, Rosenberg SA (2007) Adoptive cell transfer therapy. Semin Oncol 34:524–531

    Article  PubMed  Google Scholar 

  • Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998

    Article  PubMed  CAS  Google Scholar 

  • Dunn GP, Old LJ, Schreiber RD (2004) The three Es of cancer immunoediting. Annu Rev Immunol 22:329–360

    Article  PubMed  CAS  Google Scholar 

  • Falkson CI, Ibrahim J, Kirkwood JM, Coates AS, Atkins MB, Blum RH (1998) Phase III trial of dacarbazine versus dacarbazine with interferon alpha-2v versus dacarbazine with tamoxifen in patients with metastatic malignant melanoma: an Eastern Cooperative Oncology Group study. J Clin Oncol 16:1743–1751

    PubMed  CAS  Google Scholar 

  • Foon KA, Maluish AE, Abrams PG, et al. (1986) Recombinant leukocyte A interferon therapy for advanced hairy cell leukemia. Therapeutic and immunologic results. Am J Med. 80:351–356

    Article  PubMed  CAS  Google Scholar 

  • Furtado GC, Curotto de Lafaille MA, Kutchukhidze N, Lafaille JJ (2002) Interleukin 2 signaling is required for CD4+ regulatory T cell function. J Exp Med 196:851–857

    Article  PubMed  CAS  Google Scholar 

  • Fyfe G, Fisher RI, Rosenberg SA et al (1995) Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol 13:688–696

    PubMed  CAS  Google Scholar 

  • Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R (2008) Evidence-based and interdisciplinary consensus-based German guidelines: systemic medical treatment of melanoma in the adjuvant and palliative setting. Melanoma Res. Apr 18:152–160

    Article  CAS  Google Scholar 

  • Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65:5238–5247

    Article  PubMed  CAS  Google Scholar 

  • Gattinoni L, Powell DJ, Jr., Rosenberg SA, Restifo NP (2006) Adoptive immunotherapy for cancer: building on success. Nat Rev Immunol 6:383–393

    Article  CAS  Google Scholar 

  • Gnjatic S, Cai Z, Viguier M, Chouaib S, Guillet JG, Choppin J (1998) Accumulation of the p53 protein allows recognition by human CTL of a wild-type p53 epitope presented by breast carcinomas and melanomas. J Immunol 160:328–333

    PubMed  CAS  Google Scholar 

  • Grob JJ, Dreno B, de la SP, Delaunay M, Cupissol D, Guillot B et al (1998) Randomized trial of interferon alpha-2a as adjuvant therapy in resected primary melanoma thicker than 1.5 mm without clinically detectable node metastases. French Cooperative Group on Melanoma. Lancet 351:1905–1910

    Article  PubMed  CAS  Google Scholar 

  • Gross C, Koelch W, DeMaio A, Arispe N, Multhoff G (2003) Cell surface-bound heat shock protein 70 (Hsp70) mediates perforin-independent apoptosis by specific binding and uptake of granzyme B. J Biol Chem 278:41173–41181

    Article  PubMed  CAS  Google Scholar 

  • Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J (1997) Interferon alpha-2b combined with cytarabine versus interferon alone in chronic myelogenous leukaemia. N Engl J Med 337:223–229

    Article  PubMed  CAS  Google Scholar 

  • Gure AO, Stockert E, Scanlan MJ, Keresztes RS, Jager D, Altorki NK, Old LJ, Chen YT (2000) Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer. Proc Natl Acad Sci USA 97:4198–4203

    Article  PubMed  CAS  Google Scholar 

  • Houghton AN, Brooks H, Cote RJ, Taormina MC, Oettgen HF, Old LJ (1983) Detection of cell surface and intracellular antigens by human monoclonal antibodies. Hybrid cell lines derived from lymphocytes of patients with malignant melanoma. J Exp Med 158:53–65

    Article  PubMed  CAS  Google Scholar 

  • 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 84:506–510

    Article  PubMed  CAS  Google Scholar 

  • Kappauf H, Gallmeier WM, Wunsch PH, Mittelmeier HO, Birkmann J, Buschel G, Kaiser G, Kraus J (1997) Complete spontaneous remission in a patient with metastatic non-small-cell lung cancer. Case report, review of the literature, and discussion of possible biological pathways involved. Ann Oncol 8:1031–1039

    Article  PubMed  CAS  Google Scholar 

  • Kawakami Y, Eliyahu S, Jennings C, Sakaguchi K, Kang X, Southwood S, Robbins PF, Sette A, Appella E, Rosenberg SA (1995) Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression. J Immunol 154:3961–3968

    PubMed  CAS  Google Scholar 

  • Keilholz U, Goey SH, Punt CJ, Proebstle TM, Salzmann R, Scheibenbgen C et al (1997) Interferon alfa-2a and interleukin-2 with or without cisplatin in metastatic melanoma: a randomized trial of the European Organization for Research and Treatment of Cancer Melanoma Cooperative Group. J Clin Oncol 15:2579–2588

    PubMed  CAS  Google Scholar 

  • Kerl K, Prins C, Saurat JH, French LE (2006) Intralesional and intravenous treatment of cutaneous B-cell lymphomas with the monoclonal anti-CD20 antibody rituximab: report and follow-up of eight cases. Br J Dermatol 155:1197–1200

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood JM, Strawderman MH, Ernstoff MS, Smith TJ, Borden EC, Blum RH (1996) Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma: the Eastern Cooperative Oncology Group Trial EST 1684. J Clin Oncol 14:7–17

    PubMed  CAS  Google Scholar 

  • Kirkwood JM, Ibrahim JG, Sondak VK et al (2000) High and low-dose interferon alfa-2b in high risk melanoma: first analysis of intergroup trial E1690/S9111/C9190. J Clin Oncol 18:2444–2458

    PubMed  CAS  Google Scholar 

  • Kirkwood JM, Ibrahim JG, Sosman JA et al (2000) High-dose interferon alfa-2b significantly prolongs relapse-free and overall survival compared with GM2-KLH/QS-21 vaccine in patients with resected stage IIB-III melanoma: results of an intergroup trial E1694/S9512/C509801. J Clin Oncol 19:2370–2380

    Google Scholar 

  • Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497

    Article  PubMed  CAS  Google Scholar 

  • Koka R, Burkett PR, Chien M, Chai S, Chan F, Lodolce JP, Boone DL, Ma A (2003) Interleukin (IL)-15Rα-deficient natural killer cells survive in normal but not IL-15Rα-deficient mice. J Exp Med 197:977–984

    Article  PubMed  CAS  Google Scholar 

  • Krause SW, Rothe G, Gnad M, Reichle A, Andreesen R (2003) Blood leukocyte subsets and cytokine profile after autologous peripheral blood stem cell transplantation. Ann Hematol 82:628–636

    Article  PubMed  CAS  Google Scholar 

  • Kronenberg M (2005) Toward an understanding of NKT cell biology: progress and paradoxes. Annu Rev Immunol 23:877–900

    Article  PubMed  CAS  Google Scholar 

  • Lanzavecchia A, Sallusto F (2001) Antigen decoding by T lymphocytes: from synapses to fate determination. Nat Immunol 2:487–492

    Article  PubMed  CAS  Google Scholar 

  • Larsen SS, Egeblad M, Jaattela M, Lykkesfeldt AE (1999) Acquired antiestrogen resistance in MCF-7 human breast cancer sublines is not accomplished by altered expression of receptors in the ErbB-family. Breast Cancer Res Treat 58:41–56

    Article  PubMed  CAS  Google Scholar 

  • Lennette ET, Winberg G, Yadav M, Enblad G, Klein G (1995) Antibodies to LMP2A/2B in EBV-carrying malignancies. Eur J Cancer 31A: 1875–1878

    Article  PubMed  CAS  Google Scholar 

  • Ligibel JA, Winer EP (2002) Trastuzumab/chemotherapy combinations in metastatic breast cancer. Semin Oncol 29:38–43

    PubMed  CAS  Google Scholar 

  • Lilenbaum RC (2006) The evolving role of cetuximab in non-small cell lung cancer. Clin Cancer Res 12:4432s-4435s

    Article  PubMed  CAS  Google Scholar 

  • Lin A, Rugo HS (2007) The role of trastuzumab in early stage breast cancer: current data and treatment recommendations. Curr Treat Options Oncol 8:47–60

    Article  PubMed  Google Scholar 

  • Lyseng-Williamson KA, Robinson DM (2006) Spotlight on bevacizumab in advanced colorectal cancer, breast cancer, and non-small cell lung cancer. BioDrugs 20:193–195

    Article  PubMed  CAS  Google Scholar 

  • Ma A, Koka R, Burkett P (2006a) Diverse functions of IL-2, IL-15, and IL-7 in lymphoid homeostasis. Annu Rev Immunol 24:657–679

    Article  CAS  Google Scholar 

  • Ma XT, Xu B, An LL, Dong CY, Lin YM, Shi Y, Wu KF (2006b) Vaccine with beta-defensin 2-transduced leukemic cells activates innate and adaptive immunity to elicit potent antileukemia responses. Cancer Res 66:1169–1176

    Article  CAS  Google Scholar 

  • Mackensen A, Carcelain G, Viel S, Raynal MC, Michalaki H, Triebel F, Bosq J, Hercend T (1994) Direct evidence to support the immunosurveillance concept in a human regressive melanoma. J Clin Invest 93:1397–1402

    Article  PubMed  CAS  Google Scholar 

  • Mandruzzato S, Brasseur F, Andry G, Boon T, van der BP (1997) A CASP-8 mutation recognized by cytolytic T lymphocytes on a human head and neck carcinoma. J Exp Med 186:785–793

    Article  PubMed  CAS  Google Scholar 

  • Mantovani G, Proto E, Lai P, Turnu E, Sulis G, Puxeddu P, Del Giacco GS (1992) [Controlled trial of thymostimulin treatment of patients with primary carcinoma of the larynx resected surgically. Immunological and clinical evaluation and therapeutic prospects]. Recenti Prog Med 83:303–306

    PubMed  CAS  Google Scholar 

  • McDermott DF, Regan MM, Clark JI et al (2005) Randomized phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 23:133–141

    Article  PubMed  CAS  Google Scholar 

  • Medical Research Council Renal Cancer Collaborators (1999) Interferon-alpha and survival in metastatic renal carcinoma: early results of a randomized controlled trial. Lancet 353:14–17

    Article  Google Scholar 

  • Messing EM, Manola J, Wilding G, Propert K, Fleischmann J, Crawford ED et al (2003) Eastern Cooperative Oncology Group/Intergroup trial. Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial. J Clin Oncol 21:1214–1222

    Article  PubMed  CAS  Google Scholar 

  • Meyskens FL Jr, Kopecky K, Samson M, Hersh E, Macdonald J, Jaffe H et al (1990) Recombinant human interferon gamma: adverse effects in high-risk sag I and II cutaneous malignant melanoma. J Natl Cancer Inst 82:1071

    Article  PubMed  Google Scholar 

  • Miller JS, Soignier Y, Panoskaltsis-Mortari A, McNearney SA, Yun GH, Fautsch SK, McKenna D, Le C, Defor TE, Burns LJ, Orchard PJ, Blazar BR, Wagner JE, Slungaard A, Weisdorf DJ, Okazaki IJ, McGlave PB (2005) Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood 105:3051–3057

    Article  PubMed  CAS  Google Scholar 

  • Morimoto RI (1991) Heat shock: the role of transient inducible responses in cell damage, transformation, and differentiation. Cancer Cells 3:295–301

    PubMed  CAS  Google Scholar 

  • Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et al. (2007) Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med 356:115–124

    Article  PubMed  CAS  Google Scholar 

  • Multhoff G, Botzler C, Jennen L, Schmidt J, Ellwart J, Issels R (1997) Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol 158:4341–4350

    PubMed  CAS  Google Scholar 

  • Nair SK, Snyder D, Rouse BT, Gilboa E (1997) Regression of tumors in mice vaccinated with professional antigen-presenting cells pulsed with tumor extracts. Int J Cancer 70:706–715

    Article  PubMed  CAS  Google Scholar 

  • Negrier S, Escudier B, Lasset Ch, Doullard JY, Savary J, Chevreau Ch, Ravaud A, Mercatello A, Peny J, Mousseau M, Philip T, Tursz T (1998) Recombinant human interleukin-2, recombinant human interferon alpha-2a, or both in metastatic renal-cell carcinoma. N Engl J Med 338:1272–1278

    Article  PubMed  CAS  Google Scholar 

  • Ni CN, Redmond HP (2006) Regulatory T-cells and autoimmunity. J Surg Res 130:124–135

    Article  CAS  Google Scholar 

  • Odunsi K, Jungbluth AA, Stockert E, Qian F, Gnjatic S, Tammela J, Intengan M, Beck A, Keitz B, Santiago D, Williamson B, Scanlan MJ, Ritter G, Chen YT, Driscoll D, Sood A, Lele S, Old LJ (2003) NY-ESO-1 and LAGE-1 cancer-testis antigens are potential targets for immunotherapy in epithelial ovarian cancer. Cancer Res 63:6076–6083

    PubMed  CAS  Google Scholar 

  • Old LJ, Chen YT (1998) New paths in human cancer serology. J Exp Med 187:1163–1167

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi K, Ohno R, Tomonaga M et al (1995) A randomized trial comparing interferon-alfa with busulfan for newly diagnosed chronic myelogenous leukemia in chronic phase. Blood. 86:906–916

    PubMed  CAS  Google Scholar 

  • Parihar R, Dierksheide J, Hu Y, Carson WE (2002) IL-12 enhances the natural killer cell cytokine response to Ab-coated tumor cells. J Clin Invest 110:983–992

    PubMed  CAS  Google Scholar 

  • Pehamberger H, Soyer HP, Steiner A, Kofler R, Binder M, Mischer P et al (1998) Adjuvant interferon alfa-2a treatment in resected primary stage II cutaneous melanoma. Austrian Malignant Melanoma Cooperative Group. J Clin Oncol 16:1425–1429

    PubMed  CAS  Google Scholar 

  • Pierce SK (1994) Molecular chaperones in the processing and presentation of antigen to helper T cells. Experientia 50:1026–1030

    Article  PubMed  CAS  Google Scholar 

  • Pulendran B, Ahmed R (2006) Translating innate immunity into immunological memory: implications for vaccine development. Cell 124:849–863

    Article  PubMed  CAS  Google Scholar 

  • Quesada JR, Hersh EM, Manning J et al (1986) Treatment of hairy cell leukemia with recombinant alfa-interferon. Blood. 68:493–497

    PubMed  CAS  Google Scholar 

  • Ravandi F, O’Brien S (2006) Alemtuzumab in CLL and other lymphoid neoplasms. Cancer Invest 24:718–725

    Article  PubMed  CAS  Google Scholar 

  • Renkvist N, Castelli C, Robbins PF, Parmiani G (2001) A listing of human tumor antigens recognized by T cells. Cancer Immunol Immunother 50:3–15

    Article  PubMed  CAS  Google Scholar 

  • Ritossa P (1962) [Problems of prophylactic vaccinations of infants.]. Riv Ist Sieroter Ital 37:79–108

    PubMed  CAS  Google Scholar 

  • Robbins PF, El Gamil M, Li YF, Kawakami Y, Loftus D, Appella E, Rosenberg SA (1996) A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes. J Exp Med 183:1185–1192

    Article  PubMed  CAS  Google Scholar 

  • Robertson MJ (2002) Role of chemokines in the biology of natural killer cells. J Leukoc Biol 71:173–183

    PubMed  CAS  Google Scholar 

  • Rosenberg SA (1986) Adoptive immunotherapy of cancer using lymphokine activated killer cells and recombinant interleukin-2. Important Adv Oncol 55–91

    Google Scholar 

  • Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 319:1676–1680

    PubMed  CAS  Google Scholar 

  • Rosenberg SA, Lotze MT, Yang JC et al. (1993) Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst 85:622– 632

    Article  PubMed  CAS  Google Scholar 

  • Rudolf MP, Man S, Melief CJ, Sette A, Kast WM (2001) Human T-cell responses to HLA-A-restricted high binding affinity peptides of human papillomavirus type 18 proteins E6 and E7. Clin Cancer Res 7:788s-795s

    PubMed  CAS  Google Scholar 

  • Ruggeri L, Capanni M, Tosti A, Urbani E, Posati S, Aversa F, Martelli MF, Velardi A (2002) Innate immunity against hematological malignancies. Cytotherapy 4:343–346

    Article  PubMed  CAS  Google Scholar 

  • Sallusto F, Lanzavecchia A (2000) Understanding dendritic cell and T-lymphocyte traffic through the analysis of chemokine receptor expression. Immunol Rev 177:134–140

    Article  PubMed  CAS  Google Scholar 

  • Saltz LB (2005) Metastatic colorectal cancer: is there one standard approach? Oncology (Williston Park) 19:1147–1154

    Google Scholar 

  • Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550

    Article  PubMed  CAS  Google Scholar 

  • Scanlan MJ, Altorki NK, Gure AO, Williamson B, Jungbluth A, Chen YT, Old LJ (2000) Expression of cancer-testis antigens in lung cancer: definition of bromodomain testis-specific gene (BRDT) as a new CT gene, CT9. Cancer Lett 150:155–164

    Article  PubMed  CAS  Google Scholar 

  • Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Tureci O, Sahin U, Pfreundschuh M, Old LJ (1998) Characterization of human colon cancer antigens recognized by autologous antibodies. Int J Cancer 76:652–658

    Article  PubMed  CAS  Google Scholar 

  • Schmitt E, Parcellier A, Gurbuxani S, Cande C, Hammann A, Morales MC, Hunt CR, Dix DJ, Kroemer RT, Giordanetto F, Jaattela M, Penninger JM, Pance A, Kroemer G, Garrido C (2003) Chemosensitization by a non-apoptogenic heat shock protein 70-binding apoptosis-inducing factor mutant. Cancer Res 63:8233–8240

    PubMed  CAS  Google Scholar 

  • Schmitt E, Gehrmann M, Brunet M, Multhoff G, Garrido C (2007) Intracellular and extracellular functions of heat shock proteins: repercussions in cancer therapy. J Leukoc Biol 81:15–27

    Article  PubMed  CAS  Google Scholar 

  • Shin BK, Wang H, Yim AM, Le Naour F, Brichory F, Jang JH, Zhao R, Puravs E, Tra J, Michael CW, Misek DE, Hanash SM (2003) Global profiling of the cell surface proteome of cancer cells uncovers an abundance of proteins with chaperone function. J Biol Chem 278:7607–7616

    Article  PubMed  CAS  Google Scholar 

  • Singh AP, Moniaux N, Chauhan SC, Meza JL, Batra SK (2004) Inhibition of MUC4 expression suppresses pancreatic tumor cell growth and metastasis. Cancer Res 64:622–630

    Article  PubMed  CAS  Google Scholar 

  • Smith KA, Green JA, Eccles JM (1992) Interferon alpha 2a and vindesin in the treatment of advanced malignant melanoma. Eur J Cancer 28:438–441

    Article  PubMed  CAS  Google Scholar 

  • Smyth MJ, Trapani JA (2001) Lymphocyte-mediated immunosurveillance of epithelial cancers? Trends Immunol 22:409–411

    Article  PubMed  CAS  Google Scholar 

  • Smyth MJ, Cretney E, Takeda K, Wiltrout RH, Sedger LM, Kayagaki N, Yagita H, Okumura K (2001a) Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis. J Exp Med 193:661–670

    Article  CAS  Google Scholar 

  • Smyth MJ, Crowe NY, Godfrey DI (2001b) NK cells and NKT cells collaborate in host protection from methylcholanthrene-induced fibrosarcoma. Int Immunol 13:459–463

    Article  CAS  Google Scholar 

  • Smyth MJ, Cretney E, Kershaw MH, Hayakawa Y (2004) Cytokines in cancer immunity and immunotherapy. Immunol Rev 202:275–293

    Article  PubMed  CAS  Google Scholar 

  • Srivastava PK (1997) Purification of heat shock protein-peptide complexes for use in vaccination against cancers and intracellular pathogens. Methods 12:165–171

    Article  PubMed  CAS  Google Scholar 

  • Srivastava PK, Menoret A, Basu S, Binder RJ, McQuade KL (1998) Heat shock proteins come of age: primitive functions acquire new roles in an adaptive world. Immunity 8:657–665

    Article  PubMed  CAS  Google Scholar 

  • Stangl S, Wortmann A, Guertler U, Multhoff G (2006) Control of metastasized pancreatic carcinomas in SCID/beige mice with human IL-2/TKD-activated NK cells. J Immunol 176:6270–6276

    PubMed  CAS  Google Scholar 

  • Steinman RM, Inaba K (1999) Myeloid dendritic cells. J Leukoc Biol 66:205–208

    PubMed  CAS  Google Scholar 

  • Steplewski Z, Spira G, Blaszczyk M, Lubeck MD, Radbruch A, Illges H, Herlyn D, Rajewsky K, Scharff M (1985) Isolation and characterization of anti-monosialoganglioside monoclonal antibody 19–9 class-switch variants. Proc Natl Acad Sci USA 82:8653–8657

    Article  PubMed  CAS  Google Scholar 

  • Suttmann H, Riemensberger J, Bentien G, Schmaltz D, Stockle M, Jocham D, Bohle A, Brandau S (2006) Neutrophil granulocytes are required for effective bacillus Calmette-Guerin immunotherapy of bladder cancer and orchestrate local immune responses. Cancer Res 66:8250–8257

    Article  PubMed  CAS  Google Scholar 

  • Tindle RW (1996) Human papillomavirus vaccines for cervical cancer. Curr Opin Immunol 8:643–650

    Article  PubMed  CAS  Google Scholar 

  • Tobinai K (2007) 4. Antibody therapy for malignant lymphoma. Intern Med 46:99–100

    Article  PubMed  Google Scholar 

  • Tobinai K, Watanabe T, Ogura M, Morishima Y, Ogawa Y, Ishizawa K, Minami H, Utsunomiya A, Taniwaki M, Terauchi T, Nawano S, Matsusako M, Matsuno Y, Nakamura S, Mori S, Ohashi Y, Hayashi M, Seriu T, Hotta T (2006) Phase II study of oral fludarabine phosphate in relapsed indolent B-cell non-Hodgkin’s lymphoma. J Clin Oncol 24:174–180

    Article  PubMed  CAS  Google Scholar 

  • Trauth BC, Klas C, Peters AM, Matzku S, Moller P, Falk W, Debatin KM, Krammer PH (1989) Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science 245:301–305

    Article  PubMed  CAS  Google Scholar 

  • Trinchieri G (1989) Biology of natural killer cells. Adv Immunol 47:187–376

    Article  PubMed  CAS  Google Scholar 

  • Turley SJ (2002) Dendritic cells: inciting and inhibiting autoimmunity. Curr Opin Immunol 14:765–770

    Article  PubMed  CAS  Google Scholar 

  • Tzankov A, Ludescher C, Duba HC, Steinlechner M, Knapp R, Schmid T, Grunewald K, Gastl G, Stauder R (2001) Spontaneous remission in a secondary acute myelogenous leukaemia following invasive pulmonary aspergillosis. Ann Hematol 80:423–425

    Article  PubMed  CAS  Google Scholar 

  • Van den Eynde BJ, Boon T (1997) Tumor antigens recognized by T lymphocytes. Int J Clin Lab Res 27:81–86

    Article  PubMed  Google Scholar 

  • Van den Eynde BJ, van der Brugge BP (1997) T cell defined tumor antigens. Curr Opin Immunol 9:684–693

    Article  PubMed  Google Scholar 

  • Wang RF, Rosenberg SA (1999) Human tumor antigens for cancer vaccine development. Immunol Rev 170:85–100

    Article  PubMed  CAS  Google Scholar 

  • Wolfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281–1284

    Article  PubMed  CAS  Google Scholar 

  • Yang JC, Sherry RM, Steinberg SM et al. (2003) Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol 21:3127–3132

    Article  PubMed  CAS  Google Scholar 

  • Yang XD, Jia XC, Corvalan JR, Wang P, Davis CG, Jakobovits A (1999) Eradication of established tumors by a fully human monoclonal antibody to the epidermal growth factor receptor without concomitant chemotherapy. Cancer Res 59:1236–1243

    PubMed  CAS  Google Scholar 

  • Youde SJ, Dunbar PR, Evans EM, Fiander AN, Borysiewicz LK, Cerundolo V, Man S (2000) Use of fluorogenic histocompatibility leukocyte antigen-A*0201/HPV 16 E7 peptide complexes to isolate rare human cytotoxic T-lymphocyte-recognizing endogenous human papillomavirus antigens. Cancer Res 60:365–371

    PubMed  CAS  Google Scholar 

  • Zhang H, Chua KS, Guimond M, Kapoor V, Brown MV, Fleisher TA, Long LM, Bernstein D, Hill BJ, Douek DC, Berzofsky JA, Carter CS, Read EJ, Helman LJ, Mackall CL (2005) Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells. Nat Med 11:1238–1243

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Louboutin JP, Zhu J, Rivera AJ, Emerson SG (2002) Preterminal host dendritic cells in irradiated mice prime CD8+ T cell-mediated acute graft-versus-host disease. J Clin Invest 109:13

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675, München, Germany

    Gabriele Multhoff PhD & Sabrina T. Astner MD

Authors
  1. Gabriele Multhoff PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sabrina T. Astner MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Straße 22, 81675, München, Germany

    Michael Molls MD

  2. Institute of Physiology and Pathophysiology, University Medical Center, Duesbergweg 6, 55099, Mainz, Germany

    Peter Vaupel MD, MA

  3. Department of Internal Medicine – Oncology, Nordlandssykehuset HF Hospital, 8092, Bodø, Norway

    Carsten Nieder MD

  4. Department of Radiation Oncology, Virginia Commonwealth University School of Medicine, 401 College Street, 980058, 23298-0058, Richmond, VA, USA

    Mitchell S. Anscher MD, FACR, FACRO

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Multhoff, G., Astner, S. (2009). Role of the Immune System in Cancer Development and Therapeutic Implications. In: Molls, M., Vaupel, P., Nieder, C., Anscher, M. (eds) The Impact of Tumor Biology on Cancer Treatment and Multidisciplinary Strategies. Medical Radiology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-74386-6_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-540-74386-6_7

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-74385-9

  • Online ISBN: 978-3-540-74386-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation