The Appendix Orchestrates T-Cell Mediated Immunosurveillance in Colitis-Associated Cancer

Area of Science:

• Immunology
• Gastroenterology
• Oncology

Background:

• Appendectomy may reduce colorectal inflammation in ulcerative colitis (UC) patients.
• However, appendectomy is linked to an increased risk of colitis-associated cancer (CAC).

Purpose of the Study:

• To investigate the mechanism behind the increased risk of CAC following appendectomy in UC patients.
• To explore the role of T-cell responses in appendectomy-associated CAC.

Main Methods:

• Mice underwent appendectomy, appendicitis induction, or sham surgery, followed by CAC induction using AOM/DSS.
• Colons were analyzed for pathology and T-cell infiltration (CD3, CD8).
• Human UC patient tumors were immunophenotyped based on appendectomy history.

Main Results:

• Appendectomy reduced colitis but increased CAC number, while appendicitis induction had opposite effects.
• Intratumoral CD3+ and CD8+ T-cell densities were lower post-appendectomy.
• Blocking lymphocyte trafficking or injecting T cells modulated CAC development and T-cell infiltration.

Conclusions:

• Appendectomy may suppress T-cell priming in the appendix, a key site for immune responses.
• This suppression leads to less efficient immunosurveillance against CAC in UC patients.