The Delicate Balance of Melanoma Immunotherapy

Overview

Journal Clin Transl Immunology

Specialty Allergy & Immunology

Date 2014 Dec 16

PMID 25505953

Citations 13

Authors

David E Gyorki

Margaret Callahan

Jedd D Wolchok

Charlotte E Ariyan

Affiliations

Soon will be listed here.

Abstract

The strategy of immune modulation for the treatment of cancer is being refined with the introduction of multiple new therapeutic agents into the clinic. Melanoma is a disease where many of these agents have demonstrated efficacy. The mechanisms of action of these agents exploit the counter-regulatory mechanisms of the immune response. However, these agents are also associated with immune-related adverse events (IRAEs), which represent tissue-specific inflammatory responses. These IRAEs highlight the delicate balance of immunologic homeostasis and, with some interventions, may occur more frequently in patients who sustain a therapeutic response. This review will discuss melanoma immunogenicity and immunotherapy. Furthermore, the spectrum and distinction between a reversible immune adverse event and autoimmunity will be highlighted.

Citing Articles

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Immunotherapy in the Treatment of Metastatic Melanoma: Current Knowledge and Future Directions.

Ralli M, Botticelli A, Visconti I, Angeletti D, Fiore M, Marchetti P J Immunol Res. 2020; 2020:9235638.

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Autoimmunity and Cancer, the Paradox Comorbidities Challenging Therapy in the Context of Preexisting Autoimmunity.

Valencia J, Egbukichi N, Erwin-Cohen R J Interferon Cytokine Res. 2018; 39(1):72-84.

PMID: 30562133 PMC: 6350415. DOI: 10.1089/jir.2018.0060.

References

Mackie R, Reid R, Junor B . Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N Engl J Med. 2003; 348(6):567-8. DOI: 10.1056/NEJM200302063480620. View

Moschos S, Edington H, Land S, Rao U, Jukic D, Shipe-Spotloe J . Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon alfa-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol. 2006; 24(19):3164-71. DOI: 10.1200/JCO.2005.05.2498. View

Wolchok J, Kluger H, Callahan M, Postow M, Rizvi N, Lesokhin A . Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013; 369(2):122-33. PMC: 5698004. DOI: 10.1056/NEJMoa1302369. View

Gilhar A, Zelickson B, Ulman Y, Etzioni A . In vivo destruction of melanocytes by the IgG fraction of serum from patients with vitiligo. J Invest Dermatol. 1995; 105(5):683-6. DOI: 10.1111/1523-1747.ep12324456. View

Ahmadzadeh M, Johnson L, Heemskerk B, Wunderlich J, Dudley M, White D . Tumor antigen-specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009; 114(8):1537-44. PMC: 2927090. DOI: 10.1182/blood-2008-12-195792. View

Selby M, Engelhardt J, Quigley M, Henning K, Chen T, Srinivasan M . Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunol Res. 2014; 1(1):32-42. DOI: 10.1158/2326-6066.CIR-13-0013. View

Curran M, Montalvo W, Yagita H, Allison J . PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010; 107(9):4275-80. PMC: 2840093. DOI: 10.1073/pnas.0915174107. View

Brody J, Costantino C, Berger A, Sato T, Lisanti M, Yeo C . Expression of indoleamine 2,3-dioxygenase in metastatic malignant melanoma recruits regulatory T cells to avoid immune detection and affects survival. Cell Cycle. 2009; 8(12):1930-4. DOI: 10.4161/cc.8.12.8745. View

Dunn G, Bruce A, Ikeda H, Old L, Schreiber R . Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002; 3(11):991-8. DOI: 10.1038/ni1102-991. View

10.

Garrido F, Algarra I . MHC antigens and tumor escape from immune surveillance. Adv Cancer Res. 2001; 83:117-58. DOI: 10.1016/s0065-230x(01)83005-0. View

11.

Rosenberg S, Yang J, White D, Steinberg S . Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2: identification of the antigens mediating response. Ann Surg. 1998; 228(3):307-19. PMC: 1191483. DOI: 10.1097/00000658-199809000-00004. View

12.

Ruperto N, Lovell D, Quartier P, Paz E, Rubio-Perez N, Silva C . Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial. Lancet. 2008; 372(9636):383-91. DOI: 10.1016/S0140-6736(08)60998-8. View

13.

Thompson R, Kuntz S, Leibovich B, Dong H, Lohse C, Webster W . Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006; 66(7):3381-5. DOI: 10.1158/0008-5472.CAN-05-4303. View

14.

Beck K, Blansfield J, Tran K, Feldman A, Hughes M, Royal R . Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol. 2006; 24(15):2283-9. PMC: 2140223. DOI: 10.1200/JCO.2005.04.5716. View

15.

Klages K, Mayer C, Lahl K, Loddenkemper C, Teng M, Ngiow S . Selective depletion of Foxp3+ regulatory T cells improves effective therapeutic vaccination against established melanoma. Cancer Res. 2010; 70(20):7788-99. DOI: 10.1158/0008-5472.CAN-10-1736. View

16.

Sun T, Zhou Y, Yang M, Hu Z, Tan W, Han X . Functional genetic variations in cytotoxic T-lymphocyte antigen 4 and susceptibility to multiple types of cancer. Cancer Res. 2008; 68(17):7025-34. DOI: 10.1158/0008-5472.CAN-08-0806. View

17.

Song Y, Connor E, Li Y, Zorovich B, Balducci P, Maclaren N . The role of tyrosinase in autoimmune vitiligo. Lancet. 1994; 344(8929):1049-52. DOI: 10.1016/s0140-6736(94)91709-4. View

18.

Linsley P, Bradshaw J, Greene J, Peach R, Bennett K, Mittler R . Intracellular trafficking of CTLA-4 and focal localization towards sites of TCR engagement. Immunity. 1996; 4(6):535-43. DOI: 10.1016/s1074-7613(00)80480-x. View

19.

Jacobs J, Nierkens S, Figdor C, de Vries I, Adema G . Regulatory T cells in melanoma: the final hurdle towards effective immunotherapy?. Lancet Oncol. 2012; 13(1):e32-42. DOI: 10.1016/S1470-2045(11)70155-3. View

20.

Munn D, Mellor A . Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest. 2007; 117(5):1147-54. PMC: 1857253. DOI: 10.1172/JCI31178. View