Appendectomy is known to reduce colorectal inflammation in patients with ulcerative colitis (UC). But some data have suggested that this surgery is associated with an increased risk of colitis-associated cancer (CAC).
To confirm these data and understand its mechanism, mice underwent appendectomy, appendicitis or laparotomy. They were then exposed to azoxymethane/dextran sodium sulfate (AOM/DSS) to induce colitis-associated cancer. Human colon tumors from 21 patients with UC, who underwent surgical resection for CAC, were also studied and analyzed.
Our results show that appendectomy significantly reduced the severity of colitis and increased the number of CACs, the intratumoral densities of CD3+ and CD8+ T cells were lower. Appendicitis without appendectomy led to opposite results with less tumor, and more CD3+ and CD8+ T cells.
We blocked lymphocyte trafficking to the colon with anti-integrin antibody α4β7 or a sphingosine-1-phosphate receptor agonist, which abolished the inducing effect of appendectomy on tumor count and intratumoral CD3+/CD8+ density.
We also isolated CD8+ or CD3+ T cells from inflammatory neoappendages and injected intravenously into recipient mice treated with AOM/DSS, which increased CD3+/CD8+ T cell infiltration and decreased tumor counts.
In UC patients with a history of appendectomy, intratumoral CD3+ and CD8+ T lymphocyte densities were decreased compared to UC patients without a history of appendectomy.
We conclude that in UC, appendectomy might remove a major T-cell priming site, resulting in less effective CAC immunosurveillance.