Effect of SIgA amplification on epithelial cells of small intestine during anti-PD-L1 immunotherapy treatment [Epithelial_cells_RNAseq]

The gut microbiota is essential for many aspects of host physiology, and locally generated secretory IgA (SIgA) modulates its function. Microbiota community determines the efficacy of immune checkpoint blockade (ICB) in cancer immunotherapy. Extracellular ATP (eATP) released by the microbiota restricts the SIgA repertoire by limiting T follicular helper (Tfh) cells activity in the Peyer's Patches (PPs) via stimulation of ionotropic P2X7 receptor. Here we show that SIgA amplification by oral administration of the ATP hydrolysing enzyme apyrase corrects enteropathic features of ICB and improves the therapeutic outcome. Overall design: Epithelial cells were sorted as Zombie- EPCAM+CD45- from the ileum of MC38 tumor-bearing mice treated with anti-PD-L1 or in combination with apyrase at day 12 after tumor injection