Toshiyasu Suzuki, Anna Kilbey, Nuria Casa-Rodríguez, Amy Lawlor, Anastasia Georgakopoulou, Hannah Hayman, Kyi Lai Yin Swe, Anna Nordin, Claudio Cantù, Pierre Vantourout, Rachel A Ridgway, Ryan M Byrne, Lei Chen, Michael P Verzi, David M Gay, Ester Gil Vázquez, Hayley L Belnoue-Davis, Kathryn Gilroy, Anne Helene Køstner, Christian Kersten, Chanitra Thuwajit, Ditte K Andersen, Robert Wiesheu, Anett Jandke, Karen Blyth, Antonia K Roseweir, Simon J Leedham, Philip D Dunne, Joanne Edwards, Adrian Hayday, Owen J Sansom, Seth B Coffelt
Intraepithelial lymphocytes (IEL) expressing γδ T-cell receptors (γδTCR) play key roles in elimination of colon cancer. However, the precise mechanisms by which progressing cancer cells evade immunosurveillance by these innate T cells are unknown. Here, we investigated how loss of the Apc tumor suppressor in gut tissue could enable nascent cancer cells to escape immunosurveillance by cytotoxic γδIELs. In contrast with healthy intestinal or colonic tissue, we found that γδIELs were largely absent from the microenvironment of both mouse and human tumors, and that butyrophilin-like (BTNL) molecules, which can critically regulate γδIEL through direct γδTCR interactions, were also downregulated in tumors...
August 3, 2023: Cancer Immunology Research