Abstract
The vermiform appendix plays an important role in colorectal immunity and the homeostasis of the gut microbiome. We aimed to evaluate the prognostic value of prior appendectomy for patients with colorectal cancer (CRC). This study revealed that prior appendectomy is an independent risk factor for the prognosis of patients with CRC, based on a multicentral CRC cohort. We further demonstrated that appendectomy induced a poor prognosis of CRC through the depletion of M1 macrophage cells in AOM-induced mice, which was confirmed in age-, sex-, and location-matched patients' cohorts and orthotopic model models with the CT26 cell line. Poor responses to anti-PD-1 immunotherapy were detected in patients with CRC with appendectomy, and cetuximab is an effective treatment for patients with appendectomy-associated colorectal cancer (APD-CRC) to improve their prognosis. Our study will provide a reference for developing treatment plans for a considerable number of patients with APD-CRC, which is of great clinical significance.