Effects of Malignant Melanoma Initiating Cells on T-Cell Activation

Abstract

Although human malignant melanoma is a highly immunogenic cancer, both the endogenous antitumor immune response and melanoma immunotherapy often fail to control neoplastic progression. Accordingly, characterizing melanoma cell subsets capable of evading antitumor immunity could unravel optimized treatment strategies that might reduce morbidity and mortality from melanoma. By virtue of their preferential capacity to modulate antitumor immune responses and drive inexorable tumor growth and progression, malignant melanoma-initiating cells (MMICs) warrant closer investigation to further elucidate the cellular and molecular mechanisms underlying melanoma immune evasion and immunotherapy resistance. Here we describe methodologies that enable the characterization of immunoregulatory effects of purified MMICs versus melanoma bulk populations in coculture with syngeneic or allogeneic lymphocytes, using [3H] thymidine incorporation, enzyme-linked immunosorbent spot (ELISPOT), or ELISA assays. These assays were traditionally developed to analyze alloimmune processes and we successfully adapted them for the study of tumor-mediated immunomodulatory functions.

AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer

“…While in incipient cancer innate and adaptive immune responses may clear some tumour cells (4), cancer-initiating cells (CiC) soon instruct infiltrating immune effector cells to adapt regulatory phenotypes (5). Such active immune suppression functions are accompanied by tumour-supported accumulation of Tregs, B cells, DCs, and M2 macrophages in its microenvironment, which may contribute immunoregulatory mediators such as IL-10 or VEGF, and B cells may express alternative Th2-biased IgG4 and IgA.…”