We show that genomic inactivation of B2M in MMR-d colon cancers was associated with: (1) an elevated frequency of activated γδ T cells in ICB-naive tumours; (2) an increased presence of tumour-infiltrating γδ T cells after ICB treatment; (3) in vitro activation of tumour-infiltrating γδ T cells by CRC cell lines and PDTOs; and (4) killing of tumour cell lines by γδ T cells, in particular by Vδ1 and Vδ3 subsets expressing PD-1. Here, B2M is linked to malignant colon neoplasm.