Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity

Sci Immunol. 2024 Apr 26;9(94):eadh2334. doi: 10.1126/sciimmunol.adh2334. Epub 2024 Apr 26.


T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Humans
  • Immunotherapy / methods
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms* / immunology
  • Phospholipases A / genetics
  • Phospholipases A / immunology
  • Phospholipases A2 / immunology
  • T-Lymphocytes* / immunology
  • Up-Regulation* / immunology


  • Phospholipases A
  • Phospholipases A2
  • PLA2G10 protein, human