IMMUNOREACT 20: Immunosurveillance in rectal carcinomas with mucinous components

Background: Mucinous adenocarcinoma (MAC) of the rectum demonstrates inferior oncological outcomes compared to conventional adenocarcinoma (NOS), yet its immunological mechanisms remain incompletely characterized. Methods: In this comparative analysis of 191 rectal cancer patients (16 MAC, 175 NOS), we performed immunohistochemistry and flow cytometry on tumor and adjacent healthy mucosa. A propensity score–matched cohort (1:3 ratio; 64 patients) was analyzed to balance baseline characteristics. Results: In the unmatched cohort, MAC showed worse overall survival (HR 2.53, p=0.043) and disease-free survival (HR 2.86, p=0.013). In the matched cohort, survival differences were attenuated (OS p=0.24; DFS p=0.49). MAC demonstrated elevated CD4+ CD25+ regulatory T cells in tumors and elevated CD80+, CD8+ CD38+, and CD3+ CTLA4+ checkpoint markers in healthy mucosa of treatment-naïve patients. Post-neoadjuvant MAC showed severely reduced CD8+ CD28+ effector lymphocytes (p=0.028). Conclusions: MAC exhibits a distinct immunosuppressive microenvironment characterized by regulatory T cell activation and CD8+ T cell exhaustion, contributing to treatment resistance and poor prognosis.