Tumor-infiltrating T lymphocytes: Friends or foes?

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 nonregulatory 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.