Abstract B39: Aspirin modifies immune cell infiltration of the colonic mucosa in Lynch syndrome: a possible mechanism for cancer prevention

Abstract

Abstract The CAPP2 study showed that 600mg aspirin daily reduced the risk of colorectal cancer (CRC) in Lynch Syndrome (LS) patients. The mechanism by which this occurs is unknown. LS cancers are particularly immunogenic. Aspirin may reduce the risk of cancer in LS patients by altering the immune milieu of the colonic mucosa. We aimed to determine the density of Foxp3-positive T regulatory cells (Treg) or CD3-positive T-cells in the normal colonic mucosa of LS patients enrolled in the CAPP2 study. We then aimed to assess any links between this, aspirin use and tumour development. Serial sections (pre- and post-intervention) from normal colonic biopsies of LS patients treated with 600mg aspirin daily or placebo were immunohistochemically stained for Foxp3 and CD3. Half of the patients chosen in each treatment group developed cancer. The level of infiltration was determined by manually counting stained cells. Aspirin use increased the mean number of infiltrating Tregs from the pre- to the post-intervention biopsy (mean increase +5.33 Tregs/mm2, p=0.048) and this increase was significantly larger in the aspirin group than in the placebo group (aspirin +5.33 Tregs/mm2 v placebo -2.19 Tregs/mm2; p=0.01). There was a greater diversity of Treg counts in patients treated with aspirin compared to placebo. Total T-cell density appeared to be unaffected by aspirin. Aspirin may alter the risk of CRC development in LS patients by changing the immune infiltrate of the colon. Our results provide first evidence that aspirin influences the levels of infiltrating immune cells in the colonic mucosa of LS patients. Citation Format: Benjamin Lee Hartog, Julie Coaker, Timothy Bishop, John Mathers, Magnus von Knebel Doeberitz, John Burn, Matthias Kloor. Aspirin modifies immune cell infiltration of the colonic mucosa in Lynch syndrome: a possible mechanism for cancer prevention. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr B39.