Thailand Hub of Talents in Cancer Immunotherapy (TTCI Thailand)
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The reversibility of butyrophilin-like1 (Btnl1)-deficience in mice suggested cancer cells thrive in the absence of Vγ7+ cells, which play the pivotal role of human and mouse intraepithelial lymphocytes (IELs) expressing γδ T-cell receptors (γδTCRs) in cancer immunosurveillance. In this study, β-catenin signaling in IECs decreased expression of Btnl genes and the transcription factors that regulate them, HNF4A and HNF4G. This molecular rewiring also promoted γδ T-cell exclusion from tumors. And, the inhibition of β-catenin signaling via genetic deletion of Bcl9/Bcl9l in either Apc-deficient or mutant β-catenin mouse models restored Hnf4a, Hnf4g, and Btnl gene expression and γδ T-cell infiltration into tumors. These observations highlight an immune-evasion mechanism specific to WNT-driven colon cancer cells that disrupts γδIEL immunosurveillance and furthers cancer progression.


  1. Wellcome Trust (Seed Award 208990/Z/17/Z to SBC and Senior Clinical Research Fellowship 206314/Z/17/Z to SJL);
  2. Cancer Research UK Glasgow Centre (A25142 to SBC)
  3. Marie Skłodowska Curie Actions European Fellowship (GDCOLCA 800112 to TS)
  4. Naito Foundation Grant for Research Abroad (to TS)
  5. Medical Research Council (MR/R502327/1 to SBC & JE and MR/R502327/1 to JE)
  6. Greater Glasgow and Clyde endowment (306620-01 to JE)
  7. Cancer Research UK (Early Detection Project Grant A29834 to PD and Career Establishment Award RCCCEA-Nov21\100003 to SBC)
  8. Cancerfonden (CAN 2018/542 and 21 1572 Pj to CC)
  9. the Swedish Research Council, Vetenskapsrådet (2021-03075 to CC)
  10. Linköping University (CC); Knut and Alice Wallenberg Foundation (Wallenberg Molecular Medicine fellowship award to CC)
  11. the NIH (R01DK121915 and R01CA190558 to MV)
  12. AH was supported by Cancer Research UK core funding at the Francis Crick Institute (FC001093)
  13. OJS and KB were supported by Cancer Research UK core funding at the Cancer Research UK Beatson Institute (A17196 and A31287)

Original Paper

Title of original paper: Beta-catenin drives butyrophilin-like molecule loss and gamma delta T cell exclusion in colon cancer
Journal: Cancer Immunol Res
DOI: 10.1158/2326-6066.CIR-22-0644


Seth B. Coffelt