Immunotherapy for solid tumors--a review for surgeons

Abstract

Immunotherapy has evolved considerably in the last decade and is becoming an integral component of the armamentarium for the treatment of patients with advanced solid tumors. It is important for clinicians, especially surgeons, to understand the basic principles of novel immunotherapies and the immune system. This review summarizes the evolution of the most relevant immunotherapies, their mechanisms of action, the data supporting their clinical use, and integration of immunotherapy into multidisciplinary management of solid tumors. This review should serve as a primer for clinicians and surgeons to understand the rapidly evolving field of immunotherapy.

Keywords: Adoptive cell transfer therapy; Immunotherapy; Solid tumors.

Fig

Overview of antitumor immunity and tumor-induced immunosuppression. Left: A dendritic cell fulfills its role as a professional antigen-presenting cell. Dendritic cell process and present tumor antigen from the carcinoma cell to effector CD4 or CD8 T cells (Teff). Presentation of antigen in the context of MHC molecules, along with co-stimulatory second signals, induces Teff activation. Activated Teff produce IL-2 and interferon-gamma, which help drive a tumoricidal response. Right: Unfortunately, tumors actively promote an immunosuppressive microenvironment through several mechanisms. Tumors promote the expansion and influx of suppressor cells, including Treg and MDSCs. Treg and MDSC suppress Teff via suppressive cytokines (IL-10 and TGFβ) and PD-1 activation in Teff. Tumor cells themselves can express PD-L1, which binds to PD-1 on Teff to induce exhaustion and anergy.