HNRNPA2B1 enhances immune evasion in colorectal cancer

Immune checkpoint blockade has shown remarkable efficacy in a subset of colorectal cancers (CRCs) with high microsatellite instability (MSI-H), yet the majority of CRCs remain unresponsive, in part due to poor tumor–immune cell crosstalk. Here we identify HNRNPA2B1, an RNA-binding protein prominently upregulated in CRC, as a key modulator of the tumor immune microenvironment. Despite being central within a dysregulated network of RNA-binding proteins, HNRNPA2B1 exhibits minimal cytotoxicity to normal cells. Using mouse models and single-cell RNA-sequencing, we reveal that HNRNPA2B1 depletion enhances Cxcl9/Cxcl10–Cxcr3 signaling, elevates CD8^+ T-cell infiltration and activation, and improves antigen presentation via MHC class I. We performed single-cell RNA-sequencing (scRNA-seq) on subcutaneous tumors derived from Hnrnpa2b1-knockout (KO) and control MC38 cells (n=2 per group).