TIM-3 expression identifies a distinctive PD-1+ follicular helper T cell subset, with reduced interleukin 21 production and B cell help function in ovarian cancer patients

International Immunopharmacology
Li LiKamalibaike Maerkeya

Abstract

Follicular helper T (Tfh) cells are critical regulators of immune responses in several human malignancies. Their characteristics in ovarian cancer (OC) patients remain unclear. In this study, the circulating CD4+CXCR5+ Tfh cells was examined and compared in OC patients and non-cancer (NC) controls. Data showed that the frequency of PD-1+ Tfh cells was significantly higher in OC patients than in NC controls. Compared to PD-1- Tfh cells, PD-1+ Tfh cells presented higher interleukin (IL)-21 and IL-10 secretion and stronger proliferation. The PD-1+ Tfh cells from OC patients presented further increased IL-21 and IL-10 secretion than those from NC controls. When incubated with autologous naive B cells, PD-1+ Tfh cells from both OC patients and NC controls presented elevated capacity at inducing Ig secretion. Interestingly, TIM-3 expression was predominantly found in PD-1+ Tfh cells. Compared to TIM-3- PD-1+ Tfh cells, TIM-3+ PD-1+ Tfh cells presented significantly lower levels of IL-21 secretion and lower proliferation. In addition, TIM-3+ PD-1+ Tfh cells presented marked impairment in inducing IgM, IgG, and IgA secretion from B cells. Importantly, in OC patients, the frequencies of PD-1+ Tfh cells and TIM-3+ PD-1+ Tfh significantly...Continue Reading

Citations

Feb 10, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhifang ChenJianbing Ding
May 26, 2021·Arthritis Research & Therapy·Haruki MatsumotoKiyoshi Migita
May 29, 2021·Seminars in Cancer Biology·Stephanie LabaShoba Amarnath

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