Protein acylations in cancer immunity: effects and therapeutic opportunities

Trends Pharmacol Sci. 2025 Jul;46(7):653-673. doi: 10.1016/j.tips.2025.05.011. Epub 2025 Jun 20.

Abstract

Acylations are conserved and dynamic modifications that control various biological processes, including gene transcription and protein biology, and have been tied to diseases, such as cancers. Due to their reversible characteristic, acylations exhibit great therapeutic potential through targeting of their regulatory enzymes and proteins. Recent studies have improved our understanding of the close interplay between acylations and the tumor immune microenvironment (TIME), showing the potential to improve antitumor immune responses via acylation manipulation. Herein, we review the effects of acylations, including acetylation, lactylation, palmitoylation, and some less well-known acylations on cancer immunity, and corresponding therapeutic opportunities. Specifically, we bring into focus diverse roles of different acylation-related enzymes, metabolites, or substrates to provide insights into targeting acylations to increase antitumor immunity and generate broader research enthusiasm.

Keywords: acylation; epigenetics; immune escape; immunotherapy; post-translational modifications; tumor immune microenvironment.

Publication types

  • Review

MeSH terms

  • Acylation
  • Animals
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / metabolism
  • Tumor Microenvironment / immunology