RNA-Seq analysis of tumor and matched normal samples from colorectal cancer patients.

Tumour cells often downregulate human leukocyte antigen (HLA) class I to evade cytotoxic T lymphocyte (CTL) immunity. Although natural killer (NK) cells target MHC-I-deficient cells, many cancers bypass NK cell-mediated killing through additional immune evasion strategies. Using CRISPR-Cas9 screening, GPC2, a cell surface protein, was identified as a key suppressor of NK cell activity against HLAnull cancer cells. GPC2 is upregulated in several cancers, correlating with poor patient outcomes. In colorectal cancer, GPC2 was found to be inversely correlated with HLA class 1 expression.