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Modeling resistance of colorectal peritoneal metastases to immune checkpoint blockade in humanized mice.

Emre KüçükköseBalthasar A HeestersJulien VillaudyAndré VerheemMadalina CercelSusan van HalSylvia F BojInne H M Borel RinkesCornelis J A PuntJeanine M L RoodhartJamila LaoukiliMiriam KoopmanHergen SpitsOnno W Kranenburg
Published in: Journal for immunotherapy of cancer (2022)
By combining organoid and humanized mouse technologies, we present a novel model for spontaneous multiorgan metastasis by MSI-H CRC, in which the clinically observed organ site-dependent benefit of ICB is recapitulated. Moreover, we provide empirical evidence for a critical role for B cells in the generation of site-dependent antitumor immunity following anti-CTLA-4 treatment. High levels of immunosuppressive cytokines in ascites may underlie the observed resistance of peritoneal metastases to ICB.
Keyphrases
  • monoclonal antibody
  • high fat diet induced
  • cell free
  • combination therapy
  • insulin resistance
  • replacement therapy