Aspirin activates resolution pathways to reprogram T cell and macrophage responses in colitis-associated colorectal cancer

Roberta De Matteis, Magdalena B. Flak, Maria Gonzales-Nunez, Shani Austin-Williams, Francesco Palmas, Romain A. Colas, Jesmond Dalli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)
287 Downloads (Pure)

Abstract

Inflammation is linked with carcinogenesis in many types of cancer including colorectal cancer (CRC). Aspirin is recommended for the prevention of CRC, although the mechanism(s) mediating its immunomodulatory actions remain incompletely understood. Here, we demonstrate that aspirin increased concentrations of the immune-regulatory aspirin-triggered specialized proresolving mediators (AT-SPMs), including AT-lipoxin A4 and AT-resolvin D1, in colonic tissues during inflammation-associated CRC (I-CRC). Aspirin also down-regulated the expression of the checkpoint protein programmed cell death protein-1 in macrophages and CD8+ T cells from the colonic mucosa. Inhibition of AT-SPM biosynthesis or knockout of the AT-SPM receptor Alx/Fpr2 reversed the immunomodulatory actions of aspirin on macrophages and CD8+ T cells and abrogated its protective effects during I-CRC. Furthermore, treatment of mice with AT-SPM recapitulated the immune-directed actions of aspirin during I-CRC. Together, these findings elucidate a central role for AT-SPM in mediating the immune-directed actions of aspirin in regulating I-CRC progression.
Original languageEnglish
Article numbereabl5420
JournalScience Advances
Volume8
Issue number5
DOIs
Publication statusPublished - 2 Feb 2022

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