Skip to main content
SpringerLink
Log in
Book cover

Experimental and Applied Immunotherapy pp 229–249Cite as

Negative Regulators in Cancer Immunology and Immunotherapy

  • Chapter
  • First Online:

Abstract

It is now well established that the immune system is able to detect and destroy tumors in a process termed tumor immunosurveillance. However, the “dark side” of tumor immunity is immune evasion. That is, by the time a patient suffers from a clinically-detectable tumor, the tumor has already successfully evaded cancer immunosurveillance and often has established effective mechanisms to actively suppress the immune system, particularly in the tumor microenvironment. Therefore, cell contact-dependent and -independent immunosuppressive networks represent a significant barrier to effective immunity and immunotherapy. In this chapter, we describe some of these immunosuppressive mechanisms and components that are linked in complex networks. A better understanding of these mechanisms will eventually lead to improvements of cancer immunotherapies.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   229.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
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

Learn about institutional subscriptions

References

  1. Zhou G, Levitsky HI (2007). Natural regulatory T cells and de novo-induced regulatory T cells contribute independently to tumor-specific tolerance. J Immunol 178:2155–2162.

    PubMed  CAS  Google Scholar 

  2. Qin FX (2009). Dynamic behavior and function of Foxp3+ regulatory T cells in tumor bearing host. Cell Mol Immunol 6:3–13.

    Article  PubMed  CAS  Google Scholar 

  3. Ito T, Hanabuchi S, Wang YH et al (2008). Two functional subsets of FOXP3+ regulatory T cells in human thymus and periphery. Immunity 28:870–880.

    Article  PubMed  CAS  Google Scholar 

  4. Colombo MP, Piconese S (2007). Regulatory-T-cell inhibition versus depletion: the right choice in cancer immunotherapy. Nat Rev Cancer 7:880–887.

    Article  PubMed  CAS  Google Scholar 

  5. Curiel TJ (2008). Regulatory T cells and treatment of cancer. Curr Opin Immunol 20:241–246.

    Article  PubMed  CAS  Google Scholar 

  6. Aandahl EM, Torgersen KM, Tasken K (2008). CD8+ regulatory T cells-A distinct T-cell lineage or a transient T-cell phenotype? Hum Immunol 69:696–699.

    Article  PubMed  CAS  Google Scholar 

  7. Wang RF (2008). CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum Immunol 69:811–814.

    Article  PubMed  CAS  Google Scholar 

  8. Berzofsky JA, Terabe M (2008). NKT cells in tumor immunity: opposing subsets define a new immunoregulatory axis. J Immunol 180:3627–3635.

    PubMed  CAS  Google Scholar 

  9. Park JM, Terabe M, van den Broeke LT et al (2005). Unmasking immunosurveillance against a syngeneic colon cancer by elimination of CD4+ NKT regulatory cells and IL-13. Int J Cancer 114:80–87.

    Article  PubMed  CAS  Google Scholar 

  10. Gabrilovich DI, Nagaraj S (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174.

    Article  PubMed  CAS  Google Scholar 

  11. Kusmartsev S, Nefedova Y, Yoder D et al (2004). Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species. J Immunol 172:989–999.

    PubMed  CAS  Google Scholar 

  12. Movahedi K, Guilliams M, Van den BJ et al (2008). Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood 111:4233–4244.

    Article  PubMed  CAS  Google Scholar 

  13. Nefedova Y, Fishman M, Sherman S et al (2007). Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells. Cancer Res 67:11021–11028.

    Article  PubMed  CAS  Google Scholar 

  14. Kusmartsev S, Cheng F, Yu B et al (2003). All-trans-retinoic acid eliminates immature myeloid cells from tumor-bearing mice and improves the effect of vaccination. Cancer Res 63:4441–4449.

    PubMed  CAS  Google Scholar 

  15. Kusmartsev S, Su Z, Heiser A et al (2008). Reversal of myeloid cell-mediated immunosu p‑pression in patients with metastatic renal cell carcinoma. Clin Cancer Res 14:8270–8278.

    Article  PubMed  CAS  Google Scholar 

  16. Pan PY, Wang GX, Yin B et al (2008). Reversion of immune tolerance in advanced malignancy: modulation of myeloid-derived suppressor cell development by blockade of stem-cell factor function. Blood 111:219–228.

    Article  PubMed  CAS  Google Scholar 

  17. Rodriguez PC, Hernandez CP, Quiceno D et al (2005). Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma. J Exp Med 202:931–939.

    Article  PubMed  CAS  Google Scholar 

  18. Haas AR, Sun J, Vachani A et al (2006). Cycloxygenase-2 inhibition augments the efficacy of a cancer vaccine. Clin Cancer Res 12:214–222.

    Article  PubMed  CAS  Google Scholar 

  19. Serafini P, Meckel K, Kelso M et al (2006). Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med 203:2691–2702.

    Article  PubMed  CAS  Google Scholar 

  20. Bingle L, Brown NJ, Lewis CE (2002). The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–265.

    Article  PubMed  CAS  Google Scholar 

  21. Takayama H, Nishimura K, Tsujimura A et al (2009). Increased infiltration of tumor associated macrophages is associated with poor prognosis of bladder carcinoma in situ after intravesical bacillus Calmette-Guerin instillation. J Urol 181:1894–1900.

    Article  PubMed  CAS  Google Scholar 

  22. Allavena P, Sica A, Garlanda C et al (2008). The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev 222:155–161.

    Article  PubMed  CAS  Google Scholar 

  23. Muller AJ, Scherle PA (2006). Targeting the mechanisms of tumoral immune tolerance with small-molecule inhibitors. Nat Rev Cancer 6:613–625.

    Article  PubMed  CAS  Google Scholar 

  24. Allavena P, Sica A, Solinas G et al (2008). The inflammatory micro-environment in tumor progression: the role of tumor-associated macrophages. Crit Rev Oncol Hematol 66:1–9.

    Article  PubMed  Google Scholar 

  25. Greenhough A, Smartt HJ, Moore AE et al (2009). The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30:377–386.

    Article  PubMed  CAS  Google Scholar 

  26. Breyer RM, Bagdassarian CK, Myers SA et al (2001). Prostanoid receptors: subtypes and signaling. Annu Rev Pharmacol Toxicol 41:661–690.

    Article  PubMed  CAS  Google Scholar 

  27. Harizi H, Gualde N (2005). The impact of eicosanoids on the crosstalk between innate and adaptive immunity: the key roles of dendritic cells. Tissue Antigens 65:507–514.

    Article  PubMed  CAS  Google Scholar 

  28. Samuelsson B, Morgenstern R, Jakobsson PJ (2007). Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 59:207–224.

    Article  PubMed  CAS  Google Scholar 

  29. Bierie B, Moses HL (2006). Tumour microenvironment: TGF-b: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer 6:506–520.

    Article  PubMed  CAS  Google Scholar 

  30. Wrzesinski SH, Wan YY, Flavell RA (2007). Transforming growth factor-beta and the immune response: implications for anticancer therapy. Clin Cancer Res 13:5262–5270.

    Article  PubMed  CAS  Google Scholar 

  31. Geissmann F, Revy P, Regnault A et al (1999). TGF-b 1 prevents the noncognate maturation of human dendritic Langerhans cells. J Immunol 162:4567–4575.

    PubMed  CAS  Google Scholar 

  32. Maynard CL, Weaver CT (2008). Diversity in the contribution of interleukin-10 to T-cell-mediated immune regulation. Immunol Rev 226:219–233.

    Article  PubMed  CAS  Google Scholar 

  33. O’Garra A, Barrat FJ, Castro AG et al (2008). Strategies for use of IL-10 or its antagonists in human disease. Immunol Rev 223:114–131.

    Article  PubMed  Google Scholar 

  34. Brunet JF, Denizot F, Luciani MF et al (1987). A new member of the immunoglobulin superfamily – CTLA-4. Nature 328:267–270.

    Article  PubMed  CAS  Google Scholar 

  35. Linsley PS, Greene JL, Tan P et al (1992). Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes. J Exp Med 176:1595–1604.

    Article  PubMed  CAS  Google Scholar 

  36. Riley JL (2009). PD-1 signaling in primary T cells. Immunol Rev 229:114–125.

    Article  PubMed  CAS  Google Scholar 

  37. Waterhouse P, Penninger JM, Timms E et al (1995). Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 270:985–988.

    Article  PubMed  CAS  Google Scholar 

  38. Peggs KS, Quezada SA, Korman AJ et al (2006). Principles and use of anti-CTLA-4 antibody in human cancer immunotherapy. Curr Opin Immunol 18:206–213.

    Article  PubMed  CAS  Google Scholar 

  39. Fong L, Small EJ (2008). Anti-cytotoxic T-lymphocyte antigen-4 antibody: the first in an emerg ing class of immunomodulatory antibodies for cancer treatment. J Clin Oncol 26:5275–5283.

    Article  PubMed  CAS  Google Scholar 

  40. Attia P, Phan GQ, Maker AV et al (2005). Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 23:6043–6053.

    Article  PubMed  CAS  Google Scholar 

  41. Blank C, Mackensen A (2007). Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 56:739–745.

    Article  PubMed  Google Scholar 

  42. Gao Q, Wang XY, Qiu SJ et al (2009). Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res 15:971–979.

    Article  PubMed  CAS  Google Scholar 

  43. Barber DL, Wherry EJ, Masopust D et al (2006). Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439:682–687.

    Article  PubMed  CAS  Google Scholar 

  44. Wherry EJ, Ha SJ, Kaech SM et al (2007). Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27:670–684.

    Article  PubMed  CAS  Google Scholar 

  45. Ahmadzadeh M, Johnson LA, Heemskerk B et al (2009). Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood 114(8):1537–1544.

    Article  PubMed  CAS  Google Scholar 

  46. Nomi T, Sho M, Akahori T et al (2007). Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clin Cancer Res 13:2151–2157.

    Article  PubMed  CAS  Google Scholar 

  47. Parekh VV, Lalani S, Kim S et al (2009). PD-1/PD-L blockade prevents anergy induction and enhances the anti-tumor activities of glycolipid-activated invariant NKT cells. J Immunol 182:2816–2826.

    Article  PubMed  CAS  Google Scholar 

  48. Berger R, Rotem-Yehudar R, Slama G et al (2008). Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res 14:3044–3051.

    Article  PubMed  CAS  Google Scholar 

  49. Kammerer R, Hahn S, Singer BB et al (1998). Biliary glycoprotein (CD66a), a cell adhesion molecule of the immunoglobulin superfamily, on human lymphocytes: structure, expression and involvement in T cell activation. Eur J Immunol 28:3664–3674.

    Article  PubMed  CAS  Google Scholar 

  50. Chen Z, Chen L, Qiao SW et al (2008). Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits proximal TCR signaling by targeting ZAP-70. J Immunol 180:6085–6093.

    PubMed  CAS  Google Scholar 

  51. Kammerer R, Stober D, Singer BB et al (2001). Carcinoembryonic antigen-related cell adhesion molecule 1 on murine dendritic cells is a potent regulator of T cell stimulation. J Immunol 166:6537–6544.

    PubMed  CAS  Google Scholar 

  52. Kammerer R, Riesenberg R, Weiler C et al (2004). The tumour suppressor gene CEACAM1 is completely but reversibly downregulated in renal cell carcinoma. J Pathol 204:258–267.

    Article  PubMed  CAS  Google Scholar 

  53. Kammerer R, von Kleist S (1994). CEA expression of colorectal adenocarcinomas is correlated with their resistance against LAK-cell lysis. Int J Cancer 57:341–347.

    Article  PubMed  CAS  Google Scholar 

  54. Stern N, Markel G, Arnon TI et al (2005). Carcinoembryonic antigen (CEA) inhibits NK killing via interaction with CEA-related cell adhesion molecule 1. J Immunol 174:6692–6701.

    PubMed  CAS  Google Scholar 

  55. Markel G, Lieberman N, Katz G et al (2002). CD66a interactions between human melanoma and NK cells: a novel class I MHC-independent inhibitory mechanism of cytotoxicity. J Immunol 168:2803–2810.

    PubMed  CAS  Google Scholar 

  56. Markel G, Seidman R, Cohen Y et al (2009). Dynamic expression of protective CEACAM1 on melanoma cells during specific immune attack. Immunology 126:186–200.

    Article  PubMed  CAS  Google Scholar 

  57. Iijima H, Neurath MF, Nagaishi T et al (2004). Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J Exp Med 199:471–482.

    Article  PubMed  CAS  Google Scholar 

  58. Ball HJ, Sanchez-Perez A, Weiser S et al (2007). Characterization of an indoleamine 2,3-dio xygenase-like protein found in humans and mice. Gene 396:203–213.

    Article  PubMed  CAS  Google Scholar 

  59. Yuasa HJ, Takubo M, Takahashi A et al (2007). Evolution of vertebrate indoleamine 2,3-dio xygenases. J Mol Evol 65:705–714.

    Article  PubMed  CAS  Google Scholar 

  60. Munn DH, Zhou M, Attwood JT et al (1998). Prevention of allogeneic fetal rejection by tryptophan catabolism. Science 281:1191–1193.

    Article  PubMed  CAS  Google Scholar 

  61. Mellor AL, Munn DH (2004). IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol 4:762–774.

    Article  PubMed  CAS  Google Scholar 

  62. Mellor AL, Munn DH (2008). Creating immune privilege: active local suppression that benefits friends, but protects foes. Nat Rev Immunol 8:74–80.

    Article  PubMed  CAS  Google Scholar 

  63. Uyttenhove C, Pilotte L, Theate I et al (2003). Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med 9:1269–1274.

    Article  PubMed  CAS  Google Scholar 

  64. Yoshida N, Ino K, Ishida Y et al (2008). Overexpression of indoleamine 2,3-dioxygenase in human endometrial carcinoma cells induces rapid tumor growth in a mouse xenograft model. Clin Cancer Res 14:7251–7259.

    Article  PubMed  CAS  Google Scholar 

  65. Zheng X, Koropatnick J, Li M et al (2006). Reinstalling antitumor immunity by inhibiting tumor-derived immunosuppressive molecule IDO through RNA interference. J Immunol 177:5639–5646.

    PubMed  CAS  Google Scholar 

  66. Prendergast GC (2008). Immune escape as a fundamental trait of cancer: focus on IDO. Oncogene 27:3889–3900.

    Article  PubMed  CAS  Google Scholar 

  67. Brandacher G, Perathoner A, Ladurner R et al (2006). Prognostic value of indoleamine 2,3-dioxygenase expression in colorectal cancer: effect on tumor-infiltrating T cells. Clin Cancer Res 12:1144–1151.

    Article  PubMed  CAS  Google Scholar 

  68. Chamuleau ME, van de Loosdrecht AA, Hess CJ et al (2008). High INDO (indoleamine 2,3-dioxygenase) mRNA level in blasts of acute myeloid leukemic patients predicts poor clinical outcome. Haematologica 93:1894–1898.

    Article  PubMed  CAS  Google Scholar 

  69. Ino K, Yamamoto E, Shibata K et al (2008). Inverse correlation between tumoral indoleamine 2,3-dioxygenase expression and tumor-infiltrating lymphocytes in endometrial cancer: its association with disease progression and survival. Clin Cancer Res 14:2310–2317.

    Article  PubMed  CAS  Google Scholar 

  70. Pan K, Wang H, Chen MS et al (2008). Expression and prognosis role of indoleamine 2,3-dioxygenase in hepatocellular carcinoma. J Cancer Res Clin Oncol 134:1247–1253.

    Article  PubMed  CAS  Google Scholar 

  71. Takao M, Okamoto A, Nikaido T et al (2007). Increased synthesis of indoleamine-2,3-diox ygenase protein is positively associated with impaired survival in patients with serous-type, but not with other types of, ovarian cancer. Oncol Rep 17:1333–1339.

    PubMed  CAS  Google Scholar 

  72. Ishio T, Goto S, Tahara K et al (2004). Immunoactivative role of indoleamine 2,3-dioxygenase in human hepatocellular carcinoma. J Gastroenterol Hepatol 19:319–326.

    Article  PubMed  CAS  Google Scholar 

  73. Riesenberg R, Weiler C, Spring O et al (2007). Expression of indoleamine 2,3-dioxygenase in tumor endothelial cells correlates with long-term survival of patients with renal cell carcinoma. Clin Cancer Res 13:6993–7002.

    Article  PubMed  CAS  Google Scholar 

  74. Muller AJ, Sharma MD, Chandler PR et al (2008). Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxyg enase. Proc Natl Acad Sci USA 105:17073–17078.

    Article  PubMed  CAS  Google Scholar 

  75. Munn DH, Sharma MD, Hou D et al (2004). Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in tumor-draining lymph nodes. J Clin Invest 114:280–290.

    PubMed  CAS  Google Scholar 

  76. Hou DY, Muller AJ, Sharma MD et al (2007). Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses. Cancer Res 67:792–801.

    Article  PubMed  CAS  Google Scholar 

  77. Yen MC, Lin CC, Chen YL et al (2009). A novel cancer therapy by skin delivery of indoleamine 2,3-dioxygenase siRNA. Clin Cancer Res 15:641–649.

    Article  PubMed  CAS  Google Scholar 

  78. Metz R, Duhadaway JB, Kamasani U et al (2007). Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 67:7082–7087.

    Article  PubMed  CAS  Google Scholar 

  79. Lob S, Konigsrainer A, Schafer R et al (2008). Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 111:2152–2154.

    Article  PubMed  CAS  Google Scholar 

  80. Lob S, Konigsrainer A, Zieker D et al (2009). IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 58:153–157.

    Article  PubMed  Google Scholar 

  81. Lob S, Konigsrainer A, Rammensee HG et al (2009). Inhibitors of indoleamine-2,3-dioxyg enase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer 9:445–452.

    Article  PubMed  Google Scholar 

  82. Kudo Y, Boyd CA (2001). Characterisation of L-tryptophan transporters in human placenta: a comparison of brush border and basal membrane vesicles. J Physiol 531:405–416.

    Article  PubMed  CAS  Google Scholar 

  83. Seymour RL, Ganapathy V, Mellor AL et al (2006). A high-affinity, tryptophan-selective amino acid transport system in human macrophages. J Leukoc Biol 80:1320–1327.

    Article  PubMed  CAS  Google Scholar 

  84. Schlingensiepen KH, Fischer-Blass B, Schmaus S et al (2008). Antisense therapeutics for tumor treatment: the TGF-b 2 inhibitor AP 12009 in clinical development against malignant tumors. Recent Results Cancer Res 177:137–150.

    Article  PubMed  CAS  Google Scholar 

  85. Ribas A (2008). Overcoming immunologic tolerance to melanoma: targeting CTLA-4 with tremelimumab (CP-675,206). Oncologist 13(Suppl 4):10–15.

    Article  PubMed  CAS  Google Scholar 

  86. Bronte V, Kasic T, Gri G et al (2005). Boosting antitumor responses of T lymphocytes infiltrating human prostate cancers. J Exp Med 201:1257–1268.

    Article  PubMed  CAS  Google Scholar 

  87. Rodriguez PC, Quiceno DG, Ochoa AC (2007). L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109:1568–1573.

    Article  PubMed  CAS  Google Scholar 

  88. Baniyash M (2004). TCR zeta-chain downregulation: curtailing an excessive inflammatory immune response. Nat Rev Immunol 4:675–687.

    Article  PubMed  CAS  Google Scholar 

  89. Nagaraj S, Gupta K, Pisarev V et al (2007). Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med 13:828–835.

    Article  PubMed  CAS  Google Scholar 

  90. Pittet MJ (2009). Behavior of immune players in the tumor microenvironment. Curr Opin Oncol 21:53–59.

    Article  PubMed  Google Scholar 

  91. Breart B, Lemaitre F, Celli S et al (2008). Two-photon imaging of intratumoral CD8+ T cell cytotoxic activity during adoptive T cell therapy in mice. J Clin Invest 118:1390–1397.

    Article  PubMed  CAS  Google Scholar 

  92. Mempel TR, Pittet MJ, Khazaie K et al (2006). Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25:129–141.

    Article  PubMed  CAS  Google Scholar 

  93. Kammerer R, Zimmermann W (2010). Coevolution of activating and inhibitory receptors within mammalian carcinoembryonic antigen families. BMC Biol 4:8–12.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Immunology, Friedrich-Loeffler-Institute, Tuebingen, Germany

    Robert Kammerer

Authors
  1. Wolfgang Zimmermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert Kammerer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert Kammerer .

Editor information

Editors and Affiliations

  1. University Health Network, University of Toronto, College Street 67, Toronto, M5G 2M1, Ontario, Canada

    Jeffrey Medin

  2. National Cancer Institute, Experimental Transplatation &, National Institutes of Health, Center Drive 10, Bethesda, 20892, Maryland, USA

    Daniel Fowler

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Zimmermann, W., Kammerer, R. (2011). Negative Regulators in Cancer Immunology and Immunotherapy. In: Medin, J., Fowler, D. (eds) Experimental and Applied Immunotherapy. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-980-2_11

Download citation

Publish with us

Policies and ethics

Search

Navigation