Immune-Suppressing Cellular Elements of the Tumor Microenvironment

Abstract

Despite continual hints from preclinical and clinical research of its relevance, cancer immunology existed for many years at the periphery of cancer therapeutics. It is now the focus of intense and widespread interest after observations that blocking the activity of inhibitory receptors on T cells, known as T cell checkpoints, elicits durable clinical responses in many patients. The urgent challenge is now to understand the tissue-protective cellular elements of the tumor microenvironment (TME) that explain why the majority of patients do not respond to T cell checkpoint therapy. Analysis of human cancers and mouse models has shown that this nonresponsiveness is caused by the exclusion of T cells from the vicinity of cancer cells and that cells of the TME mediate this restriction. This review examines the immunosuppressive functions of the cells of the TME and discusses the steps of the antitumor immune reaction that, if inhibited, would diminish intratumoral T cell accumulation.