T regulatory cells and cancer immunotherapy

Abstract

The immune system is comprised of a network of regulatory and effector mechanisms that is balanced to eliminate threats to the body, while preventing uncontrolled inflammatory and auto-immune responses that would otherwise harm self. T regulatory (Treg) cells are central to this process and are required to maintain self-tolerance by actively inhibiting self-reactive T cells by a variety of direct and indirect mechanisms. Numerous studies have shown that Treg cells also exist in tumors, promote a suppressive environment that interferes with antitumor immunity, and are a major barrier to successful immunotherapy. In this review we will discuss evidence for how different types of CD4+ Treg cells are involved in antitumor immunity in both mice and humans. We also highlight strategies that have successfully inhibited Treg cells in animal models of cancer and in human clinical trials. In addition, the known effects of Treg cells on current immunotherapy approaches will be discussed. A better understanding of how Treg cells hinder antitumor immunity is required to optimize current therapeutic regimens and to make effective cancer immunotherapy a reality for an increased number of patients.