Association of COX-2 expression with lymphocyte infiltration in colorectal cancer.

Abstract

716 Background: It is proved that in colorectal cancer, Tumor infiltrating lymphocytes is associated with good prognosis. Someone pointed out that COX inhibitors act with anti-PD-1 antibody in pre-clinical models. This study aims to investigate whether COX-2 expression is associated with lymphocyte infiltration, and to know how they affect the survival. Methods: We collected specimens of resected tumor from patients who received surgery and pathological staging II and III from May 2007 to Jan 2012. These patients received surgery and adjuvant therapy with FOLFOX regimen. Tissue microarrays were made by resected tumor. Immunohistochemical staining was performed with COX-2, CD3 and CD8, PD-1 and PD-L1 antibody. Staining result of COX-2 was measured by two degrees of high and low. For CD3 and CD8, stained lymphocytes in and around tumor tissue were defined stained positive. For PD-1 and PD-L1, more 1% cells stained were defined positive stained. Results: COX-2 expression was correlated with CD3 and CD8.There were more CD3 (63.0% vs. 48.5% p=0.028) and CD8 (95.5% vs. 83.5% p=0.002) expression in the COX-2 high expression group. However, there was no significant difference in PD-1 and PD-L1 expression between COX-2 high and low expression group. As for CD3, PD-1 expression was higher in CD3 positive group than in the negative group (27.6% vs. 10.3% p=0.001). similarly, PD-L1 expression was higher in the CD3 positive group (47.3% vs. 15.2% p < 0.001). but PD-1 and PD-L1 expression was not significantly different between in the CD8 positive and negative group. Three years DFS for the whole group patient was 77.6%. There was a better tendency for 3 years DFS in the CD3 positive group (80.6% vs. 73.7%), but it was not significantly different (p=0.216). Conclusions: CD3 and CD8 expression were more in the COX-2 high expression group, which indicated COX-2 inhibitor use may act with tumor infiltrating lymphocytes. But neither PD-1 nor PD-L1 expression was correlated with COX-2 expression. Infiltrating CD3 lymphocytes may be associated with better DFS for adjuvant chemotherapy colorectal cancer patients. [Table: see text]