Abstract
Abstract It is widely believed that a hypo-and/or dysfunctional state in T cells in the elderly is a negative factor in immune defense against cancer. Accordingly, cancer patients are often excluded from immune-based clinical trials and therapies. The incidence of melanoma is rapidly rising in the elderly. To our knowledge, a critical assessment of the immune responsiveness by the elderly against a relevant melanoma associated antigen has not been carried out. Using the MART-127-35 (M27) epitope as a melanoma-associated target epitope and M27 specific T cell receptor (TCR)-engineered T cells from the elderly (over 70) and young (below 45) as common elements in the comparison, we examined the T cell responses in both cohorts to the M27 epitope and to the Influenza matrix peptide MP58-66 (Flu58) as a control, ex vivo. We also compared the expressions of a number of genes associated with immune response by real-time reverse transcription polymerase chain reaction (qPCR) in formalin fixed primary melanomas from both cohorts, in situ. While we detected a compromised CD8+ T cell response to Flu58 in the elderly, T cells from both cohorts proliferated and synthesized Th1 type cytokines in comparable levels when stimulated by the M27 epitope. qPCR analyses of primary melanomas from elderly patients showed lower levels of Fox-P3 expression but revealed comparable levels of expression of IL-2, IFNγ, TNF α, IL-4, IL-10, IDO, and TGFβ. These findings indicate that elderly patients are quite capable of responding to tumor antigens and need not be excluded from immune-based therapies or clinical trials. Citation Format: Nitya G. Chakraborty, Prashant Singh, Soheil S. Dadras, Bijay Mukherji, Upendra P. Hegde. Comparison of T cell responses to a melanoma-related antigen in elderly and young melanoma patients. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4982. doi:10.1158/1538-7445.AM2013-4982
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