Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy

Abstract

There is much promise in the use of immunotherapy for the treatment of cancer. Approaches such as those using antibodies or adoptive cell transfer can mediate complete tumor regression in a proportion of patients. However, the tumor microenvironment can inhibit immune responses leading to ineffective or suboptimal responses of tumors to immunotherapy in the majority of cases. As our knowledge of the tumor microenvironment increases, many strategies are emerging for changing the immunosuppressive nature of the tumor toward a microenvironment able to support immunity. These strategies aim to enhance the ability of immunotherapies to initiate effective immune responses able to destroy tumors. In this article, we review approaches that use immunomodulators specifically to modify the tumor microenvironment, and their use in combination with other immune-based strategies for cancer therapy.

Keywords: immunosuppression; immunotherapy; macrophages; regulatory T cells; tumor microenvironment.

Figure 1. Immune modulators of the tumor microenvironment that enhance cancer immunotherapy. Different therapies are depicted as described in the text. ATRA, all-trans retinoic acid; IDO, Indoleamine 2, 3-dioxygenase; M1 or M2, M1 or M2 macrophage; MDSC, Myeloid-derived suppressor cell; PD-1, programmed cell death protein 1; TLR, Toll-like receptor