Deciphering the complexities of cancer cell immune evasion: Mechanisms and therapeutic implications

Cancer immune evasion is one of the principal mechanisms leading to the progression and metastatization of the disease. Despite the migration and infiltration at the tumor site of immune cells, multiple factors can influence the composition of hot or "immune-sensitive" tumors and cold or "immune-resistant" tumors. Among the multiple mechanisms responsible for the make-up of the tumor microenvironment are the expression levels of major histocompatibility molecules (MHC) and of the antigen processing machinery, the metabolic network, hypoxia, and the secretion of pro-inflammatory molecules (e.g., cytokines, chemokines, and growth factors). Moreover, the different triggered pathways can mediate the reprogramming of activated, memory, effector, or regulatory/ tolerogenic subtypes of immune cells (T, NK, dendritic cells, and macrophages). Recent studies have focused on the role of cancer metabolism in evading immune surveillance through the action of the active tryptophan catabolic enzyme indoleamine 2,3-dioxygenase (IDO). Immune suppression and evasion mechanisms in cancer cells are now being extensively studied with a special focus on developing immunotherapy strategies, such as the targeting of immune checkpoints (programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1), Cytotoxic T-lymphocyte antigen-4 (CTLA-4)), adoptive cell therapy or cancer vaccines. In this review, an overview of the underlying mechanisms of cancer immune evasion and the efficacy of the therapeutic targets and agents to overcome the immune escape are described.