Tumor-Infiltrating Lymphocytes in the Checkpoint Inhibitor Era.

Abstract

Checkpoint inhibitors block co-inhibitory signals which serves to promote T cell activation/reinvigoration in the periphery and tumor microenvironment. A brief historical background as well as a summary of key observations related to the composition and prognostic value of tumor-infiltrating lymphocytes (TILs) is discussed. Solid tumor patients that respond to checkpoint inhibitors have greater CD8+ T cell densities (at the tumor margin) associated with a gene inflammation signature and high tumor mutational burden. The precise specificity of effector (CD8+ T cell) TIL remains poorly defined and this deficiency represents a major challenge for the field of cancer immunology. High mutational burden cancers such as melanoma provides compelling evidence that missense mutations create neoantigens which can serve as target antigens for the immune system. Emerging evidence suggests that neoantigen-specific TILs are the major effector cells that mediate tumor regression due to checkpoint inhibition.