Journal for immunotherapy of cancer
SIRPA drives T cell apoptosis to promote immune evasion in hepatocellular carcinoma
Par Zhang X, Ren L, Chen P et 9 autres.
Contenu en anglais
Résumé
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.