Cancer cells have developed strategies to escape and suppress the immune system which results in a failure to initiate and maintain adequate anti-tumor immunity, and consequently facilitates tumor survival and progression. Strategies include tumor antigens being only weakly immunogenic. Tumors may down regulate or modulate the expression of antigens, thus evading immune-cell detection. In addition, tumors can suppress the immune response through the synthesis of various immune suppressants that have roles in maintaining self-tolerance, or that inhibit effector immune cell function. Tumor immune suppression affects all branches of the immune system and can result in tumor escape from the immune system.
T cells (also known as T lymphocytes) are found widely distributed within tissues and the tumor environment. They play a central role in cell-mediated immunity and can mediate long-lived, antigen specific, effector and immune memory responses. T cells express T cell receptors (TCR) that confers antigenic specificity on the T cell, by recognizing an antigen ligand comprising a short contiguous amino acid sequence of a protein that is presented on the tumor cell.
Tumor cells might insufficiently stimulate antigen-presenting cells in tumor microenvironment resulting in inadequate expression of MHC class I- and II-peptide molecules, co-stimulatory molecules and cytokine production. The antigen-presenting cells therefore cannot fully engage with the TCR on the T cells and thereby leading to suboptimal T-cell activation, proliferation and expansion, resulting in T cells inability to kill tumors.
Targeting the T cell-tumor interactions and blocking their interaction to activate T cells has led to the development and approval of groundbreaking cancer immunotherapies such as Keytruda and Opdivo (anti-PD1) and Tecentriq (anti-PDL1)
