Background: This study aims to assess the expression of immune markers in non-metastatic colorectal cancers that recur after curative treatment and compare them to cancers that do not recur.

Methods: Tissue microarrays (TMAs) obtained from colorectal cancer surgical pathology specimens were stained for immune cells (CD8, FOXP3, LAG3, PU1, and PDL1); HLA I, Beta 2 Microglobulin, and HC10 on tumor cells; BRAFV600E mutation; and DNA mismatch repair (MMR) proteins. Stage I-III primary tumors which recurred/metastasized were compared to tumors which did not recur within 5 years of surgery. A logistic regression model was fit to assess the predictive effect of biomarkers on tumor recurrence.

Results: There were 141 tumors which recurred and 494 tumors which did not recur. We found a significantly lower expression of CD8, LAG3, FOXP3, PU1 and PDL1 immune cells in tumors which recurred (p<0.05). Based on multivariate analysis, only low PDL1 immune cells (adjusted OR 1.86, 1.12-3.10) predicted tumor recurrence.

Conclusion: Tumors which recur after curative surgery are associated with a state of low baseline immune response. Low expression of PDL1 on immune cells in the tumor microenvironment seems to be the most crucial prognostic biomarker associated with tumor recurrence.