%0 Journal Article
%T Dietary elaidic acid boosts tumoral antigen presentation and cancer immunity via ACSL5.
%A Lai Y
%A Gao Y
%A Lin J
%A Liu F
%A Yang L
%A Zhou J
%A Xue Y
%A Li Y
%A Chang Z
%A Li J
%A Chao T
%A Chen J
%A Cheng X
%A Gao X
%A Li X
%A Lu F
%A Chu Q
%A Wang W
%J Cell Metab
%V 36
%N 4
%D 2024 Apr 2
%M 38350448
%F 31.373
%R 10.1016/j.cmet.2024.01.012
%X 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.