CD4+ follicular helper T cell infiltration predicts breast cancer survival
(2013) Journal of Clinical Investigation — Vol. 123, n° 7, p. 2873-2892 (2013)
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- CD4<sup>+</sup> T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4<sup>+</sup> T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4<sup>+</sup> T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4<sup>+</sup> T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4<sup>+</sup> Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4<sup>+</sup> Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor.
Citations
Gu-Trantien, C., Loi, S., Garaud, S., Equeter, C., Libin, M., De Wind, A., Ravoet, M., Le Buanec, H., Sibille, C., Manfouo-Foutsop, G., Veys, I., Haibe-Kains, B., Singhal, S. K., Michiels, S., Rothé, F., Salgado, R., Duvillier, H., Ignatiadis, M., Desmedt, C., et al. (2013). CD4+ follicular helper T cell infiltration predicts breast cancer survival. Journal of Clinical Investigation, 123(7), 2873-2892. https://doi.org/10.1172/JCI67428 (Original work published 2013)