Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5

Cell Metab. 2024 Apr 2;36(4):822-838.e8. doi: 10.1016/j.cmet.2024.01.012. Epub 2024 Feb 12.


Immunomodulatory effects of long-chain fatty acids (LCFAs) and their activating enzyme, acyl-coenzyme A (CoA) synthetase long-chain family (ACSL), in the tumor microenvironment remain largely unknown. Here, we find that ACSL5 functions as an immune-dependent tumor suppressor. ACSL5 expression sensitizes tumors to PD-1 blockade therapy in vivo and the cytotoxicity mediated by CD8+ T cells in vitro via regulation of major histocompatibility complex class I (MHC-I)-mediated antigen presentation. Through screening potential substrates for ACSL5, we further identify that elaidic acid (EA), a trans LCFA that has long been considered harmful to human health, phenocopies to enhance MHC-I expression. EA supplementation can suppress tumor growth and sensitize PD-1 blockade therapy. Clinically, ACSL5 expression is positively associated with improved survival in patients with lung cancer, and plasma EA level is also predictive for immunotherapy efficiency. Our findings provide a foundation for enhancing immunotherapy through either targeting ACSL5 or metabolic reprogramming of antigen presentation via dietary EA supplementation.

Keywords: ACSL5; CD8(+) T cell; MHC class I; NLRC5; antigen presentation; checkpoint blockade; elaidic acid; immunotherapy; long-chain fatty acids.

MeSH terms

  • Antigen Presentation*
  • CD8-Positive T-Lymphocytes / metabolism
  • Coenzyme A Ligases / metabolism
  • Dietary Supplements
  • Humans
  • Neoplasms*
  • Oleic Acids*
  • Programmed Cell Death 1 Receptor
  • Tumor Microenvironment


  • elaidic acid
  • Programmed Cell Death 1 Receptor
  • ACSL5 protein, human
  • Coenzyme A Ligases
  • Oleic Acids