Mechanistic Levers of Cancer Immunotherapy: From Immune Surveillance to Immunoediting

Abstract

: Cancer immunotherapy has become a game-changing approach in oncology. Overall, the review examines the development of cancer immunotherapy, from the early immune surveillance theory to the idea of cancer immunoediting, the mechanisms of the immune system's interaction with tumors, including the immunosuppressive features of the tumor microenvironment and the mechanisms of tumor immune escape, the categorization of the main immunotherapeutic approaches and future research aims. The mechanisms of tumor immune escape, such as the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) axis, regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells, are presented. Next, the review discusses the categorization and the mechanisms of immunotherapies. Targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and PD-1/PD-L1, immune checkpoint inhibitors (ICIs) have shown significant efficacy in clinical trials. Cellular therapies like CAR-T and TCR-T advance hematologic and solid tumor treatment. Cancer vaccines, especially peptide-based and mRNA vaccines represent a rapidly developing field with encouraging preliminary clinical outcomes. Immunomodulatory drugs, including engineered cytokines and toll-like receptor agonists, provide alternative strategies to affect immune responses. Future research aims to overcome resistance, improve combination strategies, and secure lasting clinical benefits through the integration of checkpoint inhibition, adoptive cell therapy, cancer vaccination, and immunomodulation.