The Pathophysiological Impact of HLA Class Ia and HLA-G Expression and Regulatory T Cells in Malignant Melanoma: A Review

Figure 2

Schematic representation of immunological mechanisms discussed in the text that may lead to escape of malignant melanoma cells from immune surveillance. The expression of HLA class Ia molecules on the tumor cell surface may be compromised or downregulated. The tumor cell may begin, or may be selected, to express immunosuppressive HLA-G molecules that exist in both membrane-bound forms and soluble forms. Regulatory T cells in the tumor microenvironment secrete TGF-β, IL-10, and IL-35 that inhibit T cell functions. If the immune checkpoint balance is in favor of negative signals, it will result in inhibition of T cell responses with exhausted T cells and cytotoxic T lymphocytes in anergy (APC: antigen-presenting cell; CTL: cytotoxic T lymphocyte; IL-10: interleukin-10; IL-35: interleukin-35; ILT2: immunoglobulin-like transcript-2; TCR: T cell receptor; TGF-β: transforming growth factor-β; Treg: regulatory T cell).