ERC Advanced Grant · 2023
Microbiota-controlled trafficking of immunosuppressive intestinal T cells into cancer
Resistance of cancers to immune checkpoint blockade (ICB) can result from a deviated taxonomic composition of the intestinal microbiota. A surge in the Enterocloster genus, for instance following discontinuation of antibiotics or chronic inflammation caused by tumors, induces the downregulation of MAdCAM-1 in the ileal lamina propria and mesenteric lymph nodes through perturbations of biliary salts. In turn, the ileal MAdCAM-1 loss induces the exodus of immunosuppressive T lymphocytes expressing the MAdCAM-1 receptor α4β7, i.e., FoxP3+ RAR-related orphan receptor gamma t (RORγt+) regulatory (Tr17) cells, from the gut to distant tumors. Disruption of the MAdCAM-1–α4β7 axis compromises the…
From the public funding record at EU CORDIS. Describes the funded project, not the reviews below.