SIRPA drives T cell apoptosis to promote immune evasion in hepatocellular carcinoma

Background

Immune checkpoint inhibitors provide limited clinical benefit in advanced hepatocellular carcinoma (HCC), highlighting the need to identify additional mechanisms of tumor immune evasion.

Methods

We performed genome-scale CRISPR-Cas9 knockout library screening to identify genes associated with T cell apoptosis and identified differentially expressed genes in tumor-infiltrating lymphocytes from HCC patients following high-dose interleukin 2 stimulation. Integrative analysis identified signal regulatory protein alpha (SIRPA) as a candidate regulator of T cell apoptosis. SIRPA was functionally validated in vivo and in vitro using Sirpα-/- mice and primary human T cells.

Results