hnRNPA2B1 sustains antitumor T cell immunity and enhances cancer immunotherapy through IDR-dependent stabilization of chromatin-regulatory transcripts.

hnRNPA2B1 is identified as a regulator of CD8+ T cell fitness, and its loss accelerates terminal exhaustion and reduces antitumor immunity in vivo.

• Why it matters: Tumor microenvironment–driven T cell exhaustion limits cancer immunotherapy, but the epigenetic mechanisms that preserve functional tumor-infiltrating T cell states are not fully known.
• What they did: An in vivo CRISPR screen pinpointed hnRNPA2B1; patient cohort transcriptomics linked it to a proliferative, intermediate exhausted CD8+ subset with favorable clinical outcomes, and RNA stabilization of chromatin-regulatory transcripts was tested mechanistically.
• The result: hnRNPA2B1 forms nuclear puncta and stabilizes RNAs involved in chromatin organization, maintaining chromatin accessibility that restrains exhaustion programs and preserves proliferative and cytotoxic potential.