Authors: Virginie Feliu, Carlos Gomez-Roca, Marie Michelas, Noémie Thébault, Françoise Lauzéral-Vizcaino, Anna Salvioni, Lise Scandella, Emeline Sarot, Carine Valle, Camille-Charlotte Balança, Clara-Maria Scarlata, Jean-Pierre Delord, Maha Ayyoub, Christel Devaud
Published: 2023-06-08
DOI: 10.1126/sciimmunol.adg8841
Source: Full article
Despite the high prognostic value of immune infiltrates in colorectal cancer (CRC), metastatic disease remains resistant to immunotherapy by immune checkpoint blockade (ICB). Here, we show, in metastatic CRC preclinical models, that orthotopically implanted primary colon tumors exert a colon-specific antimetastatic effect on distant hepatic lesions. Enterotropic α4β7 integrin–expressing neoantigen-specific CD8 T cells were key components of the antimetastatic effect. Accordingly, the presence of concomitant colon tumors improved control of liver lesions by anti–PD-L1 proof-of-concept immunotherapy and generated protective immune memory, whereas partial depletion of α4β7