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Immune Infiltration in Human Cancer: Prognostic Significance and Disease Control

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Cancer Immunology and Immunotherapy

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 344))

Abstract

The interplay between tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses tumor−immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Thus, the fact that a strong infiltration of memory T cells with a Th1 and cytotoxic pattern is the strongest predictor for recurrence and metastasis is exemplified in colorectal cancer in which intratumoral chemokines shape an efficient immune reaction. Based on these data, we propose an immune score that predicts recurrence in early stage (UICC-TNM stage I-II) cancers. Studies on non-small lung cancers have confirmed findings of colorectal cancers and have addressed the question of the sites where antitumor immune reactions may take place. Tertiary lymphoid structures (TLS) adjacent to the tumor nest are sites of intense activity with mature dendritic cells in contact with T cells and germinal-like centers with proliferating B cells. The large number of these TLS being correlated with disease specific and overall survival tempts to postulate that they are privileged sites to mount an efficient antitumor reaction. Inflammation is a major component of human tumors and chronic inflammation is generally of bad prognosis. Head and neck cancers are highly inflammatory and two ways to modulate inflammation in these diseases are presented here: soluble IL-15 receptor α (IL-15 Rα) increases the pro-inflammatory effect of IL-15 and aggravates inflammation resulting in poor prognosis when found at high levels in the plasma of patients. By contrast, infiltration of regulatory T cells is paradoxically beneficial for local control of head and neck tumors, probably by “cooling down” the inflammatory process. The modulation of other aspects of innate immunity may also result in paradoxical effects such as the signaling through Toll like receptors 7 and 8 expressed on lung tumor cells which induce an aggressive tumoral phenotype. Finally, the analysis of primary intraocular lymphoma, which develops in the eye, exemplifies the induction of an antitumor immune reaction in an “immune sanctuary,” presenting all the complexities of the tumor–immune interplay in “open” tissues such as the colon or the lung.

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References

  • Akasaki Y, Liu G, Chung NH, Ehtesham M, Black KL, Yu JS (2004) Induction of a CD4+ T regulatory type 1 response by cyclooxygenase-2-overexpressing glioma. J Immunol 173:4352–4359

    PubMed  CAS  Google Scholar 

  • Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, Mosseri V, Laccourreye O, Bruneval P, Fridman WH, Brasnu DF, Tartour E (2006) Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res 12:465–472

    Article  PubMed  CAS  Google Scholar 

  • Badoual C, Bouchaud G, Agueznay Nel H, Mortier E, Hans S, Gey A, Fernani F, Peyrard S, -Puig PL, Bruneval P, Sastre X, Plet A, Garrigue-Antar L, Quintin-Colonna F, Fridman WH, Brasnu D, Jacques Y, Tartour E (2008) The soluble alpha chain of interleukin-15 receptor: a proinflammatory molecule associated with tumor progression in head and neck cancer. Cancer Res 68:3907–3914

    Article  PubMed  CAS  Google Scholar 

  • Badoual C, Hans S, Fridman WH, Brasnu D, Erdman S, Tartour E (2009) Revisiting the prognostic value of regulatory T cells in patients with cancer. J Clin Oncol 27:e5–e6, author reply e7

    Article  PubMed  Google Scholar 

  • Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545, Review

    Article  PubMed  CAS  Google Scholar 

  • Baratelli F, Lin Y, Zhu L, Yang SC, Heuze-Vourc'h N, Zeng G, Reckamp K, Dohadwala M, Sharma S, Dubinett SM (2005) Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol 175:1483–1490

    PubMed  CAS  Google Scholar 

  • Bergmann C, Strauss L, Zeidler R, Lang S, Whiteside TL (2007) Expansion of human T regulatory type 1 cells in the microenvironment of cyclooxygenase 2 overexpressing head and neck squamous cell carcinoma. Cancer Res 67:8865–8873

    Article  PubMed  CAS  Google Scholar 

  • Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z, Galon J (2009) ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 25:1091–1093

    Article  PubMed  CAS  Google Scholar 

  • Birkeland Sa, Hamilton-Dutoit S, Sandvej K, Andersen Hm, Bendtzen K, Møller B, Jørgensen Ka (1995) EBV-induced post-transplant lymphoproliferative disorder (PTLD). Transplant Proc 27:3467–3472

    PubMed  CAS  Google Scholar 

  • Bodaghi B (2005) New etiological concepts in uveitis. J Fr Ophtalmol 28:547–555

    Article  PubMed  CAS  Google Scholar 

  • Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27

    PubMed  CAS  Google Scholar 

  • Camus M, Tosolini M, Mlecnik B, Pages F, Kirilovsky A, Berger A, Costes A, Bindea G, Charoentong P, Bruneval P, Trajanoski Z, Fridman W-H, Galon J (2009) Coordination of intratumoral immune reaction and human colorectal cancer recurrence. Cancer Res 69:2685–2693

    Article  PubMed  CAS  Google Scholar 

  • Cassoux N, Giron A, Bodaghi B, Tran TH, Baudet S, Davy F, Chan CC, Lehoang P, Merle-Béral H (2007) IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma. Invest Ophthalmol Vis Sci 48:3253–3259

    Article  PubMed  Google Scholar 

  • Cherfils-Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, Magdeleinat P, Mami-Chouaib F, Dieu-Nosjean MC, Fridman WH, Damotte D, Sautès-Fridman C, Cremer I (2010) Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. J Clin Invest 120(4):1285–1297

    Article  PubMed  CAS  Google Scholar 

  • Ciree A, Michel L, Camilleri-Broet S, Jean Louis F, Oster M, Flageul B, Senet P, Fossiez F, Fridman WH, Bachelez H, Tartour E (2004) Expression and activity of IL-17 in cutaneous T-cell lymphomas (mycosis fungoides and Sezary syndrome). Int J Cancer 112:113–120

    Article  PubMed  CAS  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949

    Article  PubMed  CAS  Google Scholar 

  • Dalerba P, Maccalli C, Casati C, Castelli C, Parmiani G (2003) Immunology and immunotherapy of colorectal cancer. Crit Rev Oncol Hematol 46:33–57

    Article  PubMed  Google Scholar 

  • Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529–1531

    Article  PubMed  CAS  Google Scholar 

  • Dieu-Nosjean MC, Antoine M, Danel C, Heudes D, Wislez M, Poulot V, Rabbe N, Laurans L, Tartour E, De Chaisemartin L, Lebecque S, Fridman Wh, Cadranel J (2008) Long-term survival for patients with non-small-cell lung cancer with intratumoral lymphoid structures. J Clin Oncol 26:4410–4417

    Article  PubMed  CAS  Google Scholar 

  • Droemann D, Goldmann T, Branscheid D, Clark R, Dalhoff K, Zabel P, Vollmer E (2003) Toll-like receptor 2 is expressed by alveolar epithelial cells type II and macrophages in the human lung. Histochem Cell Biol 119:103–108

    PubMed  CAS  Google Scholar 

  • Droemann D, Albrecht D, Gerdes J, Ulmer AJ, Branscheid D, Vollmer E, Dalhoff K, Zabel P, Goldmann T (2005) Human lung cancer cells express functionally active Toll-like receptor 9. Respir Res 6:1

    Article  PubMed  Google Scholar 

  • Dudek AZ, Yunis C, Harrison LI, Kumar S, Hawkinson R, Cooley S, Vasilakos JP, Gorski KS, Miller JS (2007) First in human phase I trial of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced cancer. Clin Cancer Res 13:7119–7125

    Article  PubMed  CAS  Google Scholar 

  • Dunn GP, Koebel CM, Schreiber RD (2006) Interferons, immunity and cancer immunoediting. Nat Rev Immunol 6:836–848

    Article  PubMed  CAS  Google Scholar 

  • Erdman SE, Poutahidis T, Tomczak M, Rogers AB, Cormier K, Plank B, Horwitz BH, Fox JG (2003) CD4+ CD25+ regulatory T lymphocytes inhibit microbially induced colon cancer in Rag2-deficient mice. Am J Pathol 162:691–702

    Article  PubMed  CAS  Google Scholar 

  • Erdman SE, Sohn JJ, Rao VP, Nambiar PR, Ge Z, Fox JG, Schauer DB (2005) CD4+CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res 65:3998–4004

    Article  PubMed  CAS  Google Scholar 

  • Erdman SE, Rao VP, Poutahidis T, Ihrig MM, Ge Z, Feng Y, Tomczak M, Rogers AB, Horwitz BH, Fox JG (2006) CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63:6042–6050

    Google Scholar 

  • Fu J, Xu D, Liu Z, Shi M, Zhao P, Fu B, Zhang Z, Yang H, Zhang H, Zhou C, Yao J, Jin L, Wang H, Yang Y, Fu YX, Wang FS (2007) Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients. Gastroenterology 132:2328–2339

    Article  PubMed  Google Scholar 

  • Gajewska BU, Alvarez D, Vidric M, Goncharova S, Stämpfli MR, Coyle AJ, Gutierrez-Ramos JC, Jordana M (2001) Generation of experimental allergic airways inflammation in the absence of draining lymph nodes. J Clin Invest 108:577–583

    PubMed  CAS  Google Scholar 

  • Galon J, Costes A, Sanchez-Cabo F, Kirilovsky A, Berger A, Camus M, Mlecnik B, Bruneval P, Molidor R, Cugnenc P-H, Trajanoski Z, Fridman WH, Pagès F (2006) Type, density, and location of immune cells within human colorectal tumors predicts clinical outcome. Science 313:1960–1964

    Article  PubMed  CAS  Google Scholar 

  • Galon J, Fridman WH, Pages F (2007) The adaptive immunologic microenvironment in colorectal cancer: a novel perspective. Cancer Res 67:1883–1886

    Article  PubMed  CAS  Google Scholar 

  • Gould SJ, Isaacson PG (1993) Bronchus-associated lymphoid tissue (BALT) in human fetal and infant lung. J Pathol 169:229–234

    Article  PubMed  CAS  Google Scholar 

  • Greene FL, Sobin LH (2009) A worldwide approach to the TNM staging system: collaborative efforts of the AJCC and UICC. J Surg Oncol 99:269–272

    Article  PubMed  Google Scholar 

  • Gribar SC, Anand RJ, Sodhi CP, Hackam DJ (2008) The role of epithelial Toll-like receptor signaling in the pathogenesis of intestinal inflammation. J Leukoc Biol 83:493–498

    Article  PubMed  CAS  Google Scholar 

  • Halle S, Dujardin HC, Bakocevic N, Fleige H, Danzer H, Willenzon S, Suezer Y, Hämmerling G, Garbi N, Sutter G, Worbs T, Förster R (2009) Induced bronchus-associated lymphoid tissue serves as a general priming site for T cells and is maintained by dendritic cells. J Exp Med 206:2593–2601

    Article  PubMed  CAS  Google Scholar 

  • Harizi H, Juzan M, Pitard V, Moreau JF, Gualde N (2002) Cyclooxygenase-2-issued prostaglandin e(2) enhances the production of endogenous IL-10, which down-regulates dendritic cell functions. J Immunol 168:2255–2263

    PubMed  CAS  Google Scholar 

  • Hart OM, Athie-Morales V, O'Connor GM, Gardiner CM (2005) TLR7/8-mediated activation of human NK cells results in accessory cell-dependent IFN-gamma production. J Immunol 175:1636–1642

    PubMed  CAS  Google Scholar 

  • He W, Liu Q, Wang L, Chen W, Li N, Cao X (2007) TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol 44:2850–2859

    Article  PubMed  CAS  Google Scholar 

  • Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526–1529

    Article  PubMed  CAS  Google Scholar 

  • Hiraoka N, Onozato K, Kosuge T, Hirohashi S (2006) Prevalence of FOXP3+ regulatory T cells increases during the progression of pancreatic ductal adenocarcinoma and its premalignant lesions. Clin Cancer Res 12:5423–5434

    Article  PubMed  CAS  Google Scholar 

  • Johnson B, Osada T, Clay T, Lyerly H, Aorse M (2009) Physiology and therepeutics of vascular endothelial growth factor in tumor immuno-suppression. Curr nol ned 9:702–707

    Google Scholar 

  • Kawamata N, Xu B, Nishijima H, Aoyama K, Kusumoto M, Takeuchi T, Tei C, Michie SA, Matsuyama T (2009) Expression of endothelia and lymphocyte adhesion molecules in bronchus-associated lymphoid tissue (BALT) in adult human lung. Respir Res 10:97

    Article  PubMed  Google Scholar 

  • Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni L, Theoret MR, Grewal N, Spiess PJ, Antony PA, Palmer DC, Tagaya Y, Rosenberg SA, Waldmann TA, Restifo NP (2004) IL-15 enhances the in vivo antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci USA 101:1969–1974

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi H, Dubois S, Sato N, Sabzevari H, Sakai Y, Waldmann TA, Tagaya Y (2005) Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance. Blood 105:721–727

    Article  PubMed  CAS  Google Scholar 

  • Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903–907

    Article  PubMed  CAS  Google Scholar 

  • Kortylewski M, Yu H (2008) Role of Stat3 in suppressing anti-tumor immunity. Curr Opin Immunol 20:228–233

    Article  PubMed  CAS  Google Scholar 

  • Kumar H, Kawai T, Akira S (2009) Toll-like receptors and innate immunity. Biochem Biophys Res Commun 388:621–625

    Article  PubMed  CAS  Google Scholar 

  • Lamm DL (1992) Long-term results of intravesical therapy for superficial bladder cancer. Urol Clin North Am 19:573–580

    PubMed  CAS  Google Scholar 

  • Larangé A, Antonios D, Pallardy M, Kerdine-Römer S (2009) TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation. J Leukoc Biol 85:673–683

    Article  PubMed  Google Scholar 

  • Lebel-Binay S, Berger A, Zinzindohoué F, Cugnenc P, Thiounn N, Fridman WH, Pagès F (2000) Interleukin-18: biological properties and clinical implications. Eur Cytokine Netw 11:15–26

    PubMed  CAS  Google Scholar 

  • Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM, Davies DR (2008) Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320:379–381

    Article  PubMed  CAS  Google Scholar 

  • Mlecnik B, Tosolini M, Charoentong P, Kirilovsky A, Bindea G, Berger A, Camus M, Gillard M, Bruneval P, Fridman Wh, Pagès F, Trajanoski Z, Galon J (2010) Biomolecular network reconstruction reveals mechanisms of immune reaction associated with improved prognosis in colorectal cancer. Gastroenterology 138:1429–1440

    Google Scholar 

  • Mochizuki M (2009) Regional Immunity of the Eye. Acta Ophthalmol, Nov 7, Epub ahead of print

    Google Scholar 

  • Moyron-Quiroz JE, Rangel-Moreno J, Kusser K, Hartson L, Sprague F, Goodrich S, Woodland DL, Lund FE, Randall TD (2004) Role of inducible bronchus associated lymphoid tissue (iBALT) in respiratory immunity. Nat Med 10:927–934

    Article  PubMed  CAS  Google Scholar 

  • Nagpal JK, Mishra R, Das BR (2002) Activation of Stat-3 as one of the early events in tobacco chewing-mediated oral carcinogenesis. Cancer 94:2393–2400

    Article  PubMed  CAS  Google Scholar 

  • Napolitani G, Rinaldi A, Bertoni F, Sallusto F, Lanzavecchia A (2005) Selected Toll-like receptor agonist combinations synergistically trigger a T helper type 1-polarizing program in dendritic cells. Nat Immunol 6:769–776

    Article  PubMed  CAS  Google Scholar 

  • Nguyen ST, Hasegawa S, Tsuda H, Tomioka H, Ushijima M, Noda M, Omura K, Miki Y (2007) Identification of a predictive gene expression signature of cervical lymph node metastasis in oral squamous cell carcinoma. Cancer Sci 98:740–746

    Article  PubMed  CAS  Google Scholar 

  • Nussenblatt RB, Chan CC, Wilson WH, Hochman J, Gottesman M and the CNS and Ocular Lymphoma Workshop Group (2006) International Central Nervous System and Ocular Lymphoma Workshop: recommendations for the future. Ocul Immunol Inflamm 14:139–144.

    Google Scholar 

  • O'Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96:1420–1425

    Article  PubMed  Google Scholar 

  • Ohteki T, Tada H, Ishida K, Sato T, Maki C, Yamada T, Hamuro J, Koyasu S (2006) Essential roles of DC-derived IL-15 as a mediator of inflammatory responses in vivo. J Exp Med 203:2329–2338

    Article  PubMed  CAS  Google Scholar 

  • Pagès F, Berger A, Henglein B, Piqueras B, Danel C, Zinzindohoue F, Thiounn N, Cugnenc PH, Fridman WH (1999) Modulation of interleukin-18 expression in human colon carcinoma: consequences for tumor immune surveillance. Int J Cancer 84:326–330

    Article  PubMed  Google Scholar 

  • Pagès F, Berger A, Camus M, Sanchez-Cabo F, Costes A, Molidor R et al (2005) Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 353:2654–2666

    Article  PubMed  Google Scholar 

  • Pagès F, Galon J, Fridman WH (2008) The essential role of the in situ immune reaction in human colorectal cancer. J Leukoc Biol 84:981–987

    Article  PubMed  Google Scholar 

  • Pagès F, Galon J, Dieu-Nosjean MC, Tartour E, Sautes-Fridman C, Fridman WH (2010) Immune infiltration in human tumors, a prognostic factor that should not be ignored. Oncogene 29:1093–1102

    Google Scholar 

  • Pagès F, Kirilovsky A, Mlecnik B, Asslaber M, Tosolini M, Bindea G, Lagorce C, Wind P, Bruneval P, Zatloukal K, Trajanoski Z, Berger A, Fridman Wh, Galon J (2009) In situ Cytotoxic and Memory T Cells Predict Outcome in Early-Stage Colorectal Cancer Patients. J Clin Oncol 35:5944–5951

    Article  Google Scholar 

  • Ren T, Xu L, Jiao S, Wang Y, Cai Y, Liang Y, Zhou Y, Zhou H, Wen Z (2009) TLR9 signaling promotes tumor progression of human lung cancer cell in vivo. Pathol Oncol Res 15:623–630

    Google Scholar 

  • Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, Platell C, Iacopetta B (2009) Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol 27:186–192

    Article  PubMed  Google Scholar 

  • Salaun B, Coste I, Rissoan MC, Lebecque SJ, Renno T (2006) TLR3 can directly trigger apoptosis in human cancer cells. J Immunol 176:4894–4901

    PubMed  CAS  Google Scholar 

  • Salaun B, Lebecque S, Matikainen S, Rimoldi D, Romero P (2007) Toll-like receptor 3 expressed by melanoma cells as a target for therapy? Clin Cancer Res 13:4565–4574

    Article  PubMed  CAS  Google Scholar 

  • Sato Y, Goto Y, Narita N, Hoon DS (2009) Cancer Cells Expressing Toll-like Receptors and the Tumor Microenvironment. Cancer Microenviron 2(Suppl 1):205–214

    Google Scholar 

  • Seike M, Yanaihara N, Bowman ED, Zanetti KA, Budhu A, Kumamoto K, Mechanic LE, Matsumoto S, Yokota J, Shibata T, Sugimura H, Gemma A, Kudoh S, Wang XW, Harris CC (2007) Use of a cytokine gene expression signature in lung adenocarcinoma and the surrounding tissue as a prognostic classifier. J Natl Cancer Inst 99:1257–1269

    Article  PubMed  CAS  Google Scholar 

  • Shankaran V, Ikeda H, Bruce AT, White JM, Swanson PE, Old LJ, Schreiber RD (2001) IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410:1107–1111

    Article  PubMed  CAS  Google Scholar 

  • Smyth MJ, Dunn GP, Schreiber RD (2006) Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 90:1–50

    Article  PubMed  CAS  Google Scholar 

  • Tartour E, Gey A, Sastre-Garau X, Lombard Surin I, Mosseri V, Fridman WH (1998) Prognostic value of intratumoral interferon gamma messenger RNA expression in invasive cervical carcinomas. J Natl Cancer Inst 90:287–294

    Article  PubMed  CAS  Google Scholar 

  • Tartour E, Mosseri V, Jouffroy T, Deneux L, Jaulerry C, Brunin F, Fridman WH, Rodriguez J (2001) Serum soluble interleukin-2 receptor concentrations as an independent prognostic marker in head and neck cancer. Lancet 357:1263–1264

    Article  PubMed  CAS  Google Scholar 

  • Teague RM, Sather BD, Sacks JA, Huang MZ, Dossett ML, Morimoto J, Tan X, Sutton SE, Cooke MP, Ohlén C, Greenberg PD (2006) Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors. Nat Med 12:335–341

    Article  PubMed  CAS  Google Scholar 

  • Tesar BM, Chalasani G, Smith-Diggs L, Baddoura FK, Lakkis FG, Goldstein DR (2004) Direct antigen presentation by a xenograft induces immunity independently of secondary lymphoid organs. J Immunol 173:4377–4386

    PubMed  CAS  Google Scholar 

  • Thaunat O, Hanf W, Dubois V, McGregor B, Perrat G, Chauvet C, Touraine JL, Morelon E (2009) Chronic humoral rejection mediated by anti-HLA-DP alloantibodies: insights into the role of epitope sharing in donor-specific and non-donor specific alloantibodies generation. Transpl Immunol 20:209–211

    Article  PubMed  CAS  Google Scholar 

  • Tillman DK Jr, Carroll MT (2008) A 36-month clinical experience of the effectiveness of curettage and imiquimod 5% cream in the treatment of basal cell carcinoma. J Drugs Dermatol 7:s7–s14

    PubMed  Google Scholar 

  • Tissari J, Sirén J, Meri S, Julkunen I, Matikainen S (2005) IFN-alpha enhances TLR3-mediated antiviral cytokine expression in human endothelial and epithelial cells by up-regulating TLR3 expression. J Immunol 174:4289–4294

    PubMed  CAS  Google Scholar 

  • Touitou V, Daussy C, Bodaghi B, Camelo S, de Kozak Y, Lehoang P, Naud MC, Varin A, Thillaye-Goldenberg B, Merle-Béral H, Fridman WH, Sautès-Fridman C, Fisson S (2007) Impaired th1/tc1 cytokine production of tumor-infiltrating lymphocytes in a model of primary intraocular B-cell lymphoma. Invest Ophthalmol Vis Sci 48:3223–3229

    Article  PubMed  Google Scholar 

  • Tschernig T, Pabst R (2000) Bronchus-associated lymphoid tissue (BALT) is not present in the normal adult lung but in different diseases. Pathobiology 68:1–8, Review

    Article  PubMed  CAS  Google Scholar 

  • Van der Meer JW, Weening RS, Schellekens PT, van Munster IP, Nagengast FM (1993) Colorectal cancer in patients with X-linked agammaglobulinaemia. Lancet 341:1439–1440

    Article  PubMed  Google Scholar 

  • Waldmann TA (2006) The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat Rev Immunol 6:595–601, Review

    Article  PubMed  CAS  Google Scholar 

  • Wilson NJ, Boniface K, Chan JR, McKenzie BS, Blumenschein WM, Mattson JD, Basham B, Smith K, Chen T, Morel F, Lecron JC, Kastelein RA, Cua DJ, McClanahan TK, Bowman EP, de Waal Malefyt R (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8:950–957

    Article  PubMed  CAS  Google Scholar 

  • Yajima T, Nishimura H, Wajjwalku W, Harada M, Kuwano H, Yoshikai Y (2002) Overexpression of interleukin-15 in vivo enhances antitumor activity against MHC class I-negative and -positive malignant melanoma through augmented NK activity and cytotoxic T-cell response. Int J Cancer 99:573–578

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by grants from Association pour la Recherche sur le Cancer (ARC), National Cancer Institute (INCa), Canceropole Ile de France, Ville de Paris, Inserm, European Union (7FP, Geninca Consortium grant number 202230), Laboratoire Français de fractionnement et des Biotechnologies (LFB), and Pôle de Compétitivité Ile de France (Immucan). The authors wholeheartedly thank the doctoral and postdoctoral fellows, as well as the engineers and colleagues who performed the biological and statistical experiments: C. Badoual, G. Bindea, M. Camus, J. Cherfils, C. Daussy, L. de Chaisemartin, N. El Houda Afneznay, A. Gey, A. Kirilovski, C. Lagorce, L. Laurans, F. Marliot, B. Mlecnik, R. Molidor, F. Sandoval, M. Tosolini, V. Touitou, and Z. Trajanovski. They acknowledge the trustfull and enthusiastic collaboration with devoted and interactive clinicians and pathologists:M. Antoine, A. Berger, B. Bodaghi, D. Brasnu, P. Bruneval, J. Cadranel, N. Cassou, C. Danel, S. Hans, P. Le Hoang, H. Merle Béral, S. Oudart, P. Validire, P. Wind, and F. Zinzindouhé.

Author information

Authors and Affiliations

  1. INSERM U872, Centre de Recherche des Cordeliers, Paris, 75006, France

    Wolf H. Fridman, Jérome Galon, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Sylvain Fisson, Diane Damotte, Franck Pagès & Catherine Sautès-Fridman

  2. UMRS 872, Université Pierre et Marie Curie–Paris 6, Paris, 75006, France

    Wolf H. Fridman, Jérome Galon, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Sylvain Fisson, Diane Damotte, Franck Pagès & Catherine Sautès-Fridman

  3. UMRS 872, Université Paris Descartes, Paris, 75006, France

    Wolf H. Fridman, Jérome Galon, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Sylvain Fisson, Diane Damotte, Franck Pagès & Catherine Sautès-Fridman

  4. Service d’Immunologie Biologique, Hôpital Européen Georges Pompidou, AP-HP, Paris, 75015, France

    Wolf H. Fridman, Franck Pagès & Eric Tartour

  5. INSERM U872, Centre de Recherche des Cordeliers, 15 rue de l’Ecole de Médecine, Paris, 75006, France

    Wolf H. Fridman, Franck Pagès & Eric Tartour

Authors
  1. Wolf H. Fridman
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  2. Jérome Galon
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  3. Marie-Caroline Dieu-Nosjean
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  4. Isabelle Cremer
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  5. Sylvain Fisson
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  6. Diane Damotte
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  7. Franck Pagès
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  8. Eric Tartour
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  9. Catherine Sautès-Fridman
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Corresponding author

Correspondence to Wolf H. Fridman .

Editor information

Editors and Affiliations

  1. , Medical Oncology/Hematologic Neoplasial, Dana-Farber Cancer Institute, Binney Street 44, Boston, 02115, Massachusetts, USA

    Glenn Dranoff

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Fridman, W.H. et al. (2010). Immune Infiltration in Human Cancer: Prognostic Significance and Disease Control. In: Dranoff, G. (eds) Cancer Immunology and Immunotherapy. Current Topics in Microbiology and Immunology, vol 344. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2010_46

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