RT Journal Article
SR Electronic
T1 Activated B cells suppress T-cell function through metabolic competition
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e005644
DO 10.1136/jitc-2022-005644
VO 10
IS 12
A1 Imahashi, Nobuhiko
A1 Basar, Rafet
A1 Huang, Yuefan
A1 Wang, Fang
A1 Baran, Natalia
A1 Banerjee, Pinaki Prosad
A1 Lu, Junjun
A1 Nunez Cortes, Ana Karen
A1 Uprety, Nadima
A1 Ensley, Emily
A1 Muniz-Feliciano, Luis
A1 Laskowski, Tamara J
A1 Moyes, Judy S
A1 Daher, May
A1 Mendt, Mayela
A1 Kerbauy, Lucila N
A1 Shanley, Mayra
A1 Li, Li
A1 Lim, Francesca Lorraine Wei Inng
A1 Shaim, Hila
A1 Li, Ye
A1 Konopleva, Marina
A1 Green, Michael
A1 Wargo, Jennifer
A1 Shpall, Elizabeth J
A1 Chen, Ken
A1 Rezvani, Katayoun
YR 2022
UL http://jitc.bmj.com/content/10/12/e005644.abstract
AB Background B cells play a pivotal role in regulating the immune response. The induction of B cell-mediated immunosuppressive function requires B cell activating signals. However, the mechanisms by which activated B cells mediate T-cell suppression are not fully understood.Methods We investigated the potential contribution of metabolic activity of activated B cells to T-cell suppression by performing in vitro experiments and by analyzing clinical samples using mass cytometry and single-cell RNA sequencing.Results Here we show that following activation, B cells acquire an immunoregulatory phenotype and promote T-cell suppression by metabolic competition. Activated B cells induced hypoxia in T cells in a cell–cell contact dependent manner by consuming more oxygen via an increase in their oxidative phosphorylation (OXPHOS). Moreover, activated B cells deprived T cells of glucose and produced lactic acid through their high glycolytic activity. Activated B cells thus inhibited the mammalian target of rapamycin pathway in T cells, resulting in suppression of T-cell cytokine production and proliferation. Finally, we confirmed the presence of tumor-associated B cells with high glycolytic and OXPHOS activities in patients with melanoma, associated with poor response to immune checkpoint blockade therapy.Conclusions We have revealed for the first time the immunomodulatory effects of the metabolic activity of activated B cells and their possible role in suppressing antitumor T-cell responses. These findings add novel insights into immunometabolism and have important implications for cancer immunotherapy.Data are available upon reasonable request.