{Reference Type}: Journal Article
{Title}: Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.
{Author}: Lai Y;Gao Y;Lin J;Liu F;Yang L;Zhou J;Xue Y;Li Y;Chang Z;Li J;Chao T;Chen J;Cheng X;Gao X;Li X;Lu F;Chu Q;Wang W;
{Journal}: Cell Metab
{Volume}: 36
{Issue}: 4
{Year}: 2024 Apr 2
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2024.01.012
{Abstract}: 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.