Tumour Antigens Recognised by T Lymphocytes


Cancer cells bear markers (antigens) that identify them to the immune system. These antigens can be recognised by either cytotoxic or helper T lymphocytes, which can in turn produce a variety of anticancer effects, including direct lysis of tumour cells or indirect inhibition of tumour growth via the release of cytokines. Over the past two decades, the identity and structure of many different tumour antigens has been revealed via a range of different techniques. Some of these antigens are found only on tumour cells, whereas others can be found on both normal and cancerous tissues. Extensive efforts are currently underway to exploit this knowledge to develop effective therapeutic vaccines that elicit the immune system to eradicate cancer cells from the body.

Key Concepts:

  • Cancer cells bear markers (antigens) that identify them to the immune system.

  • Tumour antigens can be recognised by cytotoxic and helper T cells.

  • T cells can directly lyse tumour cells or inhibit tumour growth via cytokine release.

  • The identity and structure of many different tumour antigens are now known.

  • Tumour antigens can be classified into different groups based on their expression patterns.

  • Therapeutic vaccines that elicit the immune system to better recoginise tumour antigens have the potential to eradicate cancer cells from the body.

Keywords: tumour antigens; cytotoxic T lymphocytes; helper T lymphocytes; cancer vaccines

Figure 1.

Presentation of antigenic peptide on class I and II MHC molecules. MHC Class I‐binding peptides are classically derived from intracellular proteins. These proteins are degraded in the cytosol by the proteasome. The resulting peptides are transferred by the Transporter associated with antigen processing (TAP) to the endoplasmic reticulum (ER), where they bind to empty MHC class I molecules in association with the protein, β2 microglobulin. The resulting complex then migrates to the cell membrane where it can be recognised by CTLs. In contrast, peptides presented by MHC class II molecules originate from extracellular proteins that have been engulfed via endocytosis into vesicles where they are degraded into small peptides that then combine with class II molecules before finally reaching the cell surface. In professional APCs, class I‐binding peptides can also be derived from engulfed extracellular proteins or protein fragments via a pathway known as cross‐presentation.



Boon T, Cerottini JC, Van den Eynde B, Van den Bruggen P and Van Pel A (1994) Tumor antigens recognized by T lymphocytes. Annual Review Immunology 12: 337–365.

Bronte V and Zanovello P (2005) Regulation of immune responses by l‐arginine metabolism. Nature Reviews Immunology 5: 641–654.

Corthay A, Skovseth DK, Lundin KU et al. (2005) Primary antitumor immune response mediated by CD4+ T cells. Immunity 22(3): 371–383.

Davis ID, Chen W, Jackson H et al. (2004) Recombinant NY‐ESO‐1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans. Proceedings of the National Academy of Sciences of the USA 101: 10697–10702.

De Plaen E, Lurquin C, Lethe B et al. (1997) Identification of genes coding for tumor antigens recognized by cytolytic T lymphocytes. Methods 12: 125–142.

Demotte N, Stroobant V, Courtoy PJ et al. (2008) Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor‐infiltrating lymphocytes. Immunity 28: 414–424.

Dudley ME, Wunderlich JR, Robbins PF et al. (2002) Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 298: 850–854.

Figdor CG, de Vries IJ, Lesterhuis WJ and Melief CJ (2004) Dendritic cell immunotherapy: mapping the way. Nature Medicine 10: 475–480.

Frazer IH (2004) Prevention of cervical cancer through papillomavirus vaccination. Nature Reviews Immunology 4: 46–54.

Hodi FS, O'Day SJ, McDermott DF et al. (2010) Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine 363(8): 711–723.

Hunder NN, Wallen H, Cao J et al. (2008) Treatment of metastatic melanoma with autologous CD4+ T cells against NY‐ESO‐1. New England Journal of Medicine 358(25): 2698–2703.

Kochenderfer JN, Dudley ME, Feldman SA et al. (2012) B‐cell depletion and remissions of malignancy along with cytokine‐associated toxicity in a clinical trial of anti‐CD19 chimeric‐antigen‐receptor‐transduced T cells. Blood 119(12): 2709–2720.

Muranski P, Boni A, Antony PA et al. (2008) Tumor‐specific Th17‐polarized cells eradicate large established melanoma. Blood 112(2): 362–373.

Old LJ and Chen YT (1998) New paths in human cancer serology. Journal of Experimental Medicine 187: 1163–1167.

Pashine A, Valiante NM and Ulmer JB (2005) Targeting the innate immune response with improved vaccine adjuvants. Nature Medicine 11: S63–S68.

Quezada SA, Simpson TR, Peggs KS et al. (2010) Tumor‐reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. Journal of Experimental Medicine 207(3): 637–650.

Restifo NP, Dudley ME and Rosenberg SA (2012) Adoptive immunotherapy for cancer: harnessing the T cell response. Nature Reviews Immunology 12(4): 269–281.

Rosenberg SA, Yang JC and Restifo NP (2004) Cancer immunotherapy: moving beyond current vaccines. Nature Medicine 10: 909–915.

Sahin U, Tureci O, Schmitt H et al. (1995) Human neoplasms elicit multiple specific immune responses in the autologous host. Proceedings of the National Academy of Sciences of the USA 92(25): 11810–11813.

Simpson AJ, Caballero OL, Jungbluth A, Chen YT and Old LJ (2005) Cancer/testis antigens, gametogenesis and cancer. Nature Reviews Cancer 5: 615–625.

Spiotto MT, Rowley DA and Schreiber H (2004) Bystander elimination of antigen loss variants in established tumors. Nature Medicine 10: 294–298.

Topalian SL, Hodi FS, Brahmer JR et al. (2012) Safety, activity, and immune correlates of anti‐PD‐1 antibody in cancer. New England Journal of Medicine 366(26): 2443–2454.

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. Nature Medicine 9: 1269–1274.

Van den Eynde BJ and van der Bruggen P (1997) T cell defined tumor antigens. Current Opinion Immunology 9: 684–693.

Villa LL, Costa RL, Petta CA et al. (2005) Prophylactic quadrivalent human papillomavirus (types 6, 11, 16, and 18) L1 virus‐like particle vaccine in young women: a randomised double‐blind placebo‐controlled multicentre phase II efficacy trial. Lancet Oncology 6: 271–278.

Yu P, Rowley DA, Fu YX and Schreiber H (2006) The role of stroma in immune recognition and destruction of well‐established solid tumors. Current Opinion Immunology 18: 226–231.

Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nature Reviews Immunology 6: 295–307.

Further Reading

Blankenstein T, Coulie PG, Gilboa E et al. (2012) The determinants of tumour immunogenicity. Nature Reviews Cancer 12(4): 307–313.

Boon T, Coulie PG, Van den Eynde BJ and Van der Bruggen P (2006) Human T cell responses against melanoma. Annual Reviews of Immunology 24: 175–208.

Gilboa E (2004) The promise of cancer vaccines. Nature Reviews Cancer 4: 401–411.

Kirkwood JM, Butterfield LH, Tarhini AA et al. (2012) Immunotherapy of cancer in 2012. CA A Cancer Journal for Clinicians 62(5): 309–335.

Park TS, Rosenberg SA and Morgan RA (2011) Treating cancer with genetically engineered T cells. Trends Biotechnology 29(11): 550–557.

Scott AM, Wolchok JD and Old LJ (2012) Antibody therapy of cancer. Nature Reviews Cancer 12(4): 278–287.

TANTIGEN: Tumor T cell Antigen Database. http://cvc.dfci.harvard.edu

Vigneron N and Van den Eynde BJ (2012) Proteasome subtypes and the processing of tumor antigens: increasing antigenic diversity. Current Opinion in Immunology 24(1): 84–91.

Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nature Reviews Cancer 5: 263–274.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Pang, Ken C, Van den Eynde, Benoît J, van der Bruggen, Pierre, and Chen, Weisan(May 2013) Tumour Antigens Recognised by T Lymphocytes. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001431.pub3]