Palmitoylation modulates antitumor immunity.

Immune checkpoints (ICs) maintain immune homeostasis by suppressing excessive T-cell activation. Their dysregulated expression or signaling facilitates tumor immune evasion, thereby undermining the effectiveness of cancer immunotherapies. Palmitoylation, a reversible post-translational modification, covalently attaches palmitate to cysteine residues, altering protein localization, stability, and function. Recent studies have indicated that palmitoylation of the IC-related signaling pathway governs their membrane trafficking, signaling activity, and interactions with effector molecules, ultimately shaping anti-tumor immune responses. This review integrates the current understanding of palmitoylation mechanisms, examines their role in IC regulation, explores potential immunotherapeutic applications, and highlights future research directions.