Data from High Numbers of Differentiated Effector CD4 T Cells Are Found in Patients with Cancer and Correlate with Clinical Response after Neoadjuvant Therapy of Breast Cancer

CD4⁺ T cells influence tumor immunity in complex ways that are not fully understood. In this study, we characterized a population of human differentiated effector CD4⁺ T cells that is defined by low levels of the interleukin (IL)-2 and IL-7 receptors (CD25⁻CD127⁻). We found that this cell population expands in patients with various types of cancer, including breast cancer, to represent 2% to 20% of total CD4⁺ blood T lymphocytes as compared with only 0.2% to 2% in healthy individuals. Notably, these CD25⁻CD127⁻CD4 T cells expressed effector markers such as CD244 and CD11b with low levels of CD27, contrasting with the memory phenotype dominating this population in healthy individuals. These cells did not cycle in patients, nor did they secrete IL-10 or IL-17, but instead displayed cytotoxic features. Moreover, they encompassed oligoclonal expansions paralleling an expansion of effector CD8⁺ T cells that included tumor antigen–specific T cells. During neoadjuvant chemotherapy in patients with breast cancer, we found that the increase in CD25⁻CD127⁻ CD4⁺ T cells correlated with tumor regression. This observation suggested that CD4⁺ T cells included tumor antigen–specific cells, which may be generated by or participate in tumor regressions during chemotherapy. In summary, our results lend support to the hypothesis that CD4⁺ T cells are involved in human antitumor responses. Cancer Res; 74(8); 2204–16. ©2014 AACR.