Tumours: Immunotherapy


The mainstay of cancer treatment has historically involved therapies, such as surgery, chemotherapy or radiation, that were developed without regard for the patient's immune system. However, as researchers have started to elucidate mechanisms by which the immune system can eradicate cancerous cells, an increasing number of approaches have been developed that capitalise on an immune‐based antitumour response. These therapies include nonspecific activation of the immune system using toll‐like receptor ligands, cytokines or immune checkpoint inhibitors, or specific treatments, like monoclonal antibody administration or vaccination, that directly target cancer cells. Perhaps, the most promising specific therapy is the adoptive transfer of genetically engineered tumour‐reactive T cells, an approach that has already proven curative in some patients with metastatic disease. Cumulatively, these new immune‐based approaches have great promise to revolutionise cancer therapy. In this article, we will outline the mechanisms and characteristics of these tumour immunotherapies, emphasising those with demonstrated clinical efficacy.

Key Concepts:

  • The immune system can destroy malignant cells.

  • The tumour microenvironment enables tumour growth by exerting immunosuppression.

  • Restoring the immune system's ability to fight cancers is a promising clinical approach.

  • Nonspecific immunotherapies include administration of toll‐like receptor ligands, cytokines or immune‐checkpoint inhibiting antibodies.

  • Specific immunotherapies include administration of monoclonal antibodies, adoptive T cell transfer or vaccination.

Keywords: adoptive transfer; cancer; cytokines; immunotherapy; toll‐like receptors; vaccination

Figure 1.

Generalized scheme of adoptive cell transfer (ACT) of genetically modified T cells. In ACT, T cells from a cancer patient‘s peripheral blood are genetically modified to recognize the tumor ex vivo and reinfused into the patient. Reprinted from January 2013 issue of Progressnotes (MUSChealth.com/progressnotes), with permission of the Medical University of South Carolina. Image by Emma Vought. All rights retained.



Adler MJ and Dimitrov DS (2012) Therapeutic antibodies against cancer. Hematology/Oncology Clinics of North America 26(3): 447–481, vii.

Barber DL, Wherry EJ, Masopust D et al. (2006) Restoring function in exhausted CD8T cells during chronic viral infection. Nature 439(7077): 682–687.

Bolhassani A, Safaiyan S and Rafati S (2011) Improvement of different vaccine delivery systems for cancer therapy. Molecular Cancer 10: 3.

Brahmer JR, Tykodi SS, Chow LQM et al. (2012) Safety and activity of anti‐PD‐L1 antibody in patients with advanced cancer. New England Journal of Medicine 366(26): 2455–2465.

Brunda MJ, Luistro L, Warrier RR et al. (1993) Antitumour and antimetastatic activity of interleukin 12 against murine tumours. Journal of Experimental Medicine 178(4): 1223–1230.

Cluff CW (2010) Monophosphoryl lipid A (MPL) as an adjuvant for anti‐cancer vaccines: clinical results. Advances in Experimental Medicine and Biology 667: 111–123.

Di Stasi A, Tey SK, Dotti G et al. (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. New England Journal of Medicine 365(18): 1673–1683.

Dong H, Strome SE, Salomao DR et al. (2002) Tumour‐associated B7‐H1 promotes T‐cell apoptosis: a potential mechanism of immune evasion. Nature Medicine 8(8): 793–800.

Dranoff G (2004) Cytokines in cancer pathogenesis and cancer therapy. Nature Reviews Cancer 4(1): 11–22.

Draube A, Klein‐Gonzalez N, Mattheus S et al. (2011) Dendritic cell based tumour vaccination in prostate and renal cell cancer: a systematic review and meta‐analysis. PloS One 6(4): e18801.

Forni G, Fujiwara H, Martino F et al. (1988) Helper strategy in tumour immunology: expansion of helper lymphocytes and utilization of helper lymphokines for experimental and clinical immunotherapy. Cancer Metastasis Reviews 7(4): 289–309.

Frampton JE (2012) Catumaxomab: in malignant ascites. Drugs 72(10): 1399–1410.

Heine H (2011) TLRs, NLRs and RLRs: innate sensors and their impact on allergic diseases‐‐a current view. Immunology Letters 139(1–2): 14–24.

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.

Iwai Y, Ishida M, Tanaka Y et al. (2002) Involvement of PD‐L1 on tumour cells in the escape from host immune system and tumour immunotherapy by PD‐L1 blockade. Proceedings of the National Academy of Sciences of the USA 99(19): 12293–12297.

Janeway CA Jr (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symposia on Quantitative Biology 54(Pt 1): 1–13.

Kantoff PW, Schuetz TJ, Blumenstein BA et al. (2010) Overall survival analysis of a phase II randomized controlled trial of a Poxviral‐based PSA‐targeted immunotherapy in metastatic castration‐resistant prostate cancer. Journal of Clinical Oncology 28(7): 1099–1105.

Kaufman HL (2012) Vaccines for melanoma and renal cell carcinoma. Seminars in Oncology 39(3): 263–275.

Kerkar SP, Goldszmid RS, Muranski P et al. (2011) IL‐12 triggers a programmatic change in dysfunctional myeloid‐derived cells within mouse tumours. Journal of Clinical Investigation 121(12): 4746–4757.

Kirkwood JM, Ibrahim JG, Sosman JA et al. (2001) High‐dose interferon alfa‐2b significantly prolongs relapse‐free and overall survival compared with the GM2‐KLH/QS‐21 vaccine in patients with resected stage IIB‐III melanoma: results of intergroup trial E1694/S9512/C509801. Journal of Clinical Oncology 19(9): 2370–2380.

Larocca C and Schlom J (2011) Viral vector‐based therapeutic cancer vaccines. Cancer Journal 17(5): 359–371.

Leonard JP, Sherman ML, Fisher GL et al. (1997) Effects of single‐dose interleukin‐12 exposure on interleukin‐12‐associated toxicity and interferon‐gamma production. Blood 90(7): 2541–2548.

Lowy DR and Schiller JT (2006) Prophylactic human papillomavirus vaccines. Journal of Clinical Investigation 116(5): 1167–1173.

Mahvi DM, Henry MB, Albertini MR et al. (2007) Intratumoural injection of IL‐12 plasmid DNA – results of a phase I/IB clinical trial. Cancer Gene Therapy 14(8): 717–723.

Matzinger P (1994) Tolerance, danger, and the extended family. Annual Review of Immunology 12: 991–1045.

Mellman I, Coukos G and Dranoff G (2011) Cancer immunotherapy comes of age. Nature 480(7378): 480–489.

Nagorsen D and Thiel E (2006) Clinical and immunologic responses to active specific cancer vaccines in human colorectal cancer. Clinical Cancer Research 12(10): 3064–3069.

Negrier S, Maral J, Drevon M et al. (2000) Long‐term follow‐up of patients with metastatic renal cell carcinoma treated with intravenous recombinant interleukin‐2 in Europe. Cancer Journal from Scientific American 6(suppl. 1): S93–S98.

Okazaki T, Iwai Y and Honjo T (2002) New regulatory co‐receptors: inducible co‐stimulator and PD‐1. Current Opinion in Immunology 14(6): 779–782.

Paulos CM, Wrzesinski C, Kaiser A et al. (2007) Microbial translocation augments the function of adoptively transferred self/tumour‐specific CD8+ T cells via TLR4 signaling. Journal of Clinical Investigation 117(8): 2197–2204.

Porter DL, Levine BL, Kalos M, Bagg A and June CH (2011) Chimeric antigen receptor‐modified T cells in chronic lymphoid leukemia. New England Journal of Medicine 365(8): 725–733.

Postow MA, Callahan MK, Barker CA et al. (2012) Immunologic correlates of the abscopal effect in a patient with melanoma. New England Journal of Medicine 366(10): 925–931.

Qureshi OS, Zheng Y, Nakamura K et al. (2011) Trans‐endocytosis of CD80 and CD86: a molecular basis for the cell‐extrinsic function of CTLA‐4. Science (New York) 332(6029): 600–603.

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 (1986) Adoptive immunotherapy of cancer using lymphokine activated killer cells and recombinant interleukin‐2. Important Advances in Oncology 55–91.

Rosenberg SA, Yang JC, Sherry RM et al. (2011) Durable complete responses in heavily pretreated patients with metastatic melanoma using T‐cell transfer immunotherapy. Clinical Cancer Research 17(13): 4550–4557.

Rosenberg SA, Yang JC, Topalian SL et al. (1994) Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high‐dose bolus interleukin 2. Journal of the American Medical Association 271(12): 907–913.

Salem ML and Cole DJ (2010) Dendritic cell recovery post‐lymphodepletion: a potential mechanism for anti‐cancer adoptive T cell therapy and vaccination. Cancer Immunology, Immunotherapy 59(3): 341–353.

Schiessl C, Wolber C, Tauber M, Offner F and Strohal R (2007) Treatment of all basal cell carcinoma variants including large and high‐risk lesions with 5% imiquimod cream: histological and clinical changes, outcome, and follow‐up. Journal of Drugs in Dermatology 6(5): 507–513.

Schreiber RD, Old LJ and Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science (New York) 331(6024): 1565–1570.

Schwartzentruber DJ, Lawson DH, Richards JM et al. (2011) gp100 peptide vaccine and interleukin‐2 in patients with advanced melanoma. New England Journal of Medicine 364(22): 2119–2127.

Seya T, Akazawa T, Tsujita T and Matsumoto M (2006) Role of Toll‐like receptors in adjuvant‐augmented immune therapies. Evidence‐Based Complementary and Alternative Medicine 3(1): 31–38.

Shackleton M, Davis ID, Hopkins W et al. (2004) The impact of imiquimod, a Toll‐like receptor‐7 ligand (TLR7L), on the immunogenicity of melanoma peptide vaccination with adjuvant Flt3 ligand. Cancer Immunity 4: 9.

Speiser DE, Lienard D, Rufer N et al. (2005) Rapid and strong human CD8+ T cell responses to vaccination with peptide, IFA, and CpG oligodeoxynucleotide 7909. Journal of Clinical Investigation 115(3): 739–746.

Stewart JH 4th and Levine EA (2011) Role of bacillus Calmette‐Guerin in the treatment of advanced melanoma. Expert Review of Anticancer Therapy 11(11): 1671–1676.

Tivol EA, Borriello F, Schweitzer AN et al. (1995) Loss of CTLA‐4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA‐4. Immunity 3(5): 541–547.

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.

Vermorken JB, Claessen AM, van Tinteren H et al. (1999) Active specific immunotherapy for stage II and stage III human colon cancer: a randomised trial. Lancet 353(9150): 345–350.

Zuiverloon TC, Nieuweboer AJ, Vekony H et al. (2012) Markers predicting response to bacillus Calmette‐Guerin immunotherapy in high‐risk bladder cancer patients: a systematic review. European Urology 61(1): 128–145.

Further Reading

Chow MT, Moller A and Smyth MJ (2012) Inflammation and immune surveillance in cancer. Seminars in Cancer Biology 22(1): 23–32.

Krysko DV, Garg AD, Kaczmarek A et al. (2012) Immunogenic cell death and DAMPs in cancer therapy. Nature Reviews Cancer 12(12): 860–875.

Lee S and Margolin K (2011) Cytokines in cancer immunotherapy. Cancers 3: 3856–3893.

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

* Required Field

How to Cite close
Johnson, C Bryce, Salem, Mohamed L, Mehrotra, Shikhar, Cole, David J, and Rubinstein, Mark P(Jun 2013) Tumours: Immunotherapy. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001432.pub3]