Secretory IgA amplification during immune checkpoint blockade enhances the control of tumor growth by enterotropic T cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41042869.
- Also identified by DOI 10.1126/sciadv.aeb5308 and PMC identifier 12494019.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>FH</sub>) 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, <i>IgA<sup>-/-</sup></i> mice did not show any improvement of antitumor response by apyrase administration. Mechanistically, data in mice and patients with cancer suggest that invigorated enterotropic cytotoxic T cells expressing the chemokine receptor CCR9 replenish the tumor microenvironment in a CCL25-mediated manner and control tumor growth, resulting in improved ICB efficacy.
Medical subject headings
- Immune Checkpoint Inhibitors
- Immunoglobulin A, Secretory
- Neoplasms