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

• Published in: Nature immunology Vol. 20; no. 9; pp. 1220 - 1230
• Main Authors: Wang, Lei, Simons, Diana L., Lu, Xuyang, Tu, Travis Y., Solomon, Shawn, Wang, Roger, Rosario, Anthony, Avalos, Christian, Schmolze, Daniel, Yim, John, Waisman, James, Lee, Peter P.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01-09-2019; Nature Publishing Group
• Subjects: 631/250; 631/67; Biomedical and Life Sciences; Biomedicine; Breast cancer; CCR8 protein; CD45RA antigen; Cytokines; Immunology; Infectious Diseases; Lymphocytes; Lymphocytes T; Peripheral blood; Subpopulations; Tumor microenvironment
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/s41590-019-0429-7

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.