Connecting blood and intratumoral Treg cell activity in predicting future relapse in breast cancer

Regulatory T (T reg ) cells play a major role in the development of an immunosuppressive tumor microenvironment. The origin of intratumoral T reg cells and their relationship with peripheral blood T reg cells remain unclear. T reg cells consist of at least three functionally distinct subpopulations. Here we show that peripheral blood CD45RA − FOXP3 hi T reg cells (T reg II cells) are phenotypically closest to intratumoral T reg cells, including in their expression of CCR8. Analyses of T cell antigen receptor repertoires further support the hypothesis that intratumoral T reg cells may originate primarily from peripheral blood T reg II cells. Moreover, the signaling responsiveness of peripheral blood T reg II cells to immunosuppressive, T helper type 1 (T H 1) and T helper type 2 (T H 2) cytokines reflects intratumoral immunosuppressive potential, and predicts future relapse in two independent cohorts of patients with breast cancer. Together, our findings give important insights into the relationship between peripheral blood T reg cells and intratumoral T reg cells, and highlight cytokine signaling responsiveness as a key determinant of intratumoral immunosuppressive potential and clinical outcome. T reg cells obstruct effective anticancer responses. Lee and colleagues describe a T reg cell biomarker signature that is strongly associated with enhanced suppression and progression of human breast cancer.