MHC class i antigens and the tumor microenvironment

Abstract

Cancer is characterized by the accumulation of multiple genetic events leading to malignant transformation and escape from the immune surveillance. A complex interaction of malignant cells with the surrounding tissues, including epithelial cells, vascular and lymphatic vessels, extracellular matrix, cytokines, chemokines, and infiltrating immune cells, lead to tumor immunoediting and generation of tumor escape variants with an increased ability to disseminate to distant sites. Tumor- infiltrating cytotoxic T-lymphocytes (TILs) are responsible for tumor cell recognition and elimination, while Major Histocompatibility Complex (MHC) class I and II products play a central role in mounting an effective anti-tumor immune response by restricting T cell recognition of foreign antigens (Ags) processed as small peptides. Therefore, tumor cells that fail to express MHC molecules have an advantage that provides them with an escape route from T cell immunity. The molecular identification of human cancer antigens has allowed the development of antigen-specific immunotherapy. Novel cancer vaccines aim to induce tumor-specific effector T cells that can reduce the tumor mass and to induce tumor-specific memory T cells that can control tumor relapse. However, loss of tumor MHC class I expression may compromise the efficacy of the immunotherapy-induced anti-tumor T cell immunity. Early cancer detection and treatment require more effective cancer biomarkers, or molecular signatures, for diagnosis, prognosis, and therapeutic efficacy. Analysis of the tumor expression of HLA class I antigens as biomarkers of cancer development might help to choose an appropriate treatment protocol and monitor clinical response to cancer immunotherapy.