Perioperative Cimetidine Administration Enhances Tumor Infiltration Lymphocytes and HLA-DR Expression in Colorectal Cancer

Abstract

Objective: It has been shown in our previous study that cimetidine (CIM) can boost the hosts' cellular immunity in patients with gastrointestinal cancer. This study was conducted to evaluate CIM's effects on tumor infiltrating lymphocytes (TIL) and HLA-DR expression in tumor stroma in colorectal cancer (CRC), so as to investigate its role in local immune response at the tumor site in CRC. Methods: Forty-nine CRC patients were randomized into treatment group of 25 patients who took CIM 7 days before curative surgery till the operation day, and control group of 24 patients who received similar treatment except for CIM intervention. TIL responses and HLA-DR expression were studied on tumor tissues taken before and after surgical resection. Results: The percentage of significant TIL response was increased from 32% (8/25) to 76% (19/25) (P<0.005) in the CIM treatment group, whereas there were no significant changes in TIL response in the control group [25% (6/24) at recruitment vs. 33% (8/24) at operation, P>0.50]. Moreover, the percentages of HLA-DR expression were increased from 36% (9/25) to 72% (18/25) in the CIM treatment group, but there were no significant differences in HLA-DR expression in the control group [41.7% (10/24) before resection vs 45.8% (11/24) after resection, P>0.50]. Conclusion: CIM used before surgery might promote TIL responses and increase the HLA-DR expression in stroma cells in CRC patients, leading to enhanced host immunity against tumor.