IMMUNOREACT 4: Peritumoral microenvironment as a predictor of anastomotic leak after surgery for rectal cancer

Background Anastomotic leak (AL) remains a critical complication following rectal cancer surgery. The roleof the immune microenvironment of the healthy rectal mucosa surrounding rectal cancer has never beeninvestigated as a predictor of AL after rectal surgery.Methods IMMUNOREACT 4 is a sub-analysis of the IMMUNOREACT project (clinicaltrials.gov NCT04915326and NCT04915326), enrolling patients who underwent colorectal anastomosis for rectal cancer. A panel ofimmunohistochemistry markers of immune surveillance (CD3, CD4, CD8alpha, CD8beta, Tbet, FoxP3, CD80and PD-L1) and a panel of flow cytometry markers (CD3+CTLA-4+, CD4+CD25+FoxP3+, CD8+CD28+ andCD8+CD38+, CK+CD80+, CK+CD86+ and CK+HLAabc+) were tested. We compared predictive modelscombining constitutive immune predictors with clinical variables against a purely clinical model.Results At flow cytometry, CK+HLAabc+ MFI (AUC 0.66, 95% CI 0.52 to 0.80), CD8+CD38+ cell rate (AUC0.65, 95% CI 0.52 to 0.78), and CD3+CTLA4+ cell rate (AUC 0.65, 95% CI 0.51 to 0.80) showed moderatepredictive potential for AL. At immunohistochemistry, CD3+ (AUC 0.57, 95% CI 0.54 to 0.60), CD8+ (AUC0.57, 95% CI 0.52 to 0.62), CD8β+ (AUC 0.59, 95% CI 0.53 to 0.65) and Tbet+ (AUC 0.60, 95% CI 0.56 to 0.64)showed some predictive ability for AL. The model including CD8β+, BMI, neutrophile/lymphocyte ratio,tumor location, had an AUC of 0.67 (95% CI 0.62 to 0.72).Conclusions Although the predictive accuracy of our models remains relatively limited, combining immunemicroenvironmental data from the healthy mucosa with clinical variables may represent a promisingapproach to identify patients at risk of AL.