Tumor-infiltrating T lymphocytes: friends or foes?

Abstract

The prognostic significance of tumor-infiltrating lymphocytes (TILs) has been a longstanding topic of debate. In cases where TILs have improved patient outcome, T lymphocytes are recognized as the main effectors of antitumor immune responses. However, recent studies have revealed that a subset of CD4(+) T cells, referred to as CD4(+)CD25(+) regulatory T cells (Treg), may accumulate in the tumor environment and suppress tumor-specific T-cell responses, thereby hindering tumor rejection. Hence, predicting tumor behavior on the basis of an indiscriminate evaluation of tumor-infiltrating T cells may result in inconsistent prognostic accuracy. The presence of infiltrating CD4(+)CD25(+) Treg may be detrimental to the host defense against the tumor, while the presence of effector T lymphocytes, including CD8(+) T cells and non-regulatory CD4(+) helper T cells may be beneficial. Enhanced recruitment of antitumor effector T lymphocytes to tumor tissue in addition to inhibition of local Treg, may therefore be an ideal target for improving cancer immunotherapy. This article reviews the antitumor functions of T-lymphocytes, with special attention given to CD4(+) regulatory T-cells within the tumor environment.