Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells.

ABSTRACT: The gut microbiota is essential for many aspects of host physiology, and secretory immunoglobulin A (sIgA) modulates its function. The microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy; however, mechanisms able to improve this function are not known. Extracellular adenosine triphosphate (ATP) released by the microbiota restricts the sIgA repertoire by limiting T follicular helper (T_FH) cell activity in the Peyer's patches via stimulation of the ionotropic P2X7 receptor. We show that sIgA amplification by oral administration of the ATP hydrolyzing enzyme apyrase corrects enteropathic features of ICB and improves therapeutic efficacy. Consistent with sIgA function in reshaping the gut ecosystem and enhancing ICB, IgA^-/

SUBMITTER: De Ponte Conti B 

PROVIDER: S-EPMC12494019 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature