[Characteristics of CD8+ T cell infiltration in colorectal cancer and their correlation with prognosis]

Objective: As cytotoxic T cells, CD8+ T lymphocytes can kill tumor cells by releasing perforin and other effector molecules, but the correlation between their infiltration level and the prognosis of colorectal cancer varies in previous studies. This study aims to explore the distribution of CD8+T cells in tumor center and invasive margin of colorectal cancer, and to analyze their correlation with the prognosis of patients. Methods: A retrospective cohort study was used to analyze the clinicopathological features of 221 patients with colorectal cancer from the colorectal cancer pathological database of the Sixth Affiliated Hospital of Sun Yat-sen University between 2009 and 2012. Case inclusion criteria: (1) colorectal cancers confirmed by postoperative pathology; (2) patients with follow-up data. Exclusion criteria: (1) multiple primary cancers; (2) inflammatory bowel disease, Lynch syndrome or familial adenomatous polyposis; (3) no available paraffin slides; (4) patients receiving preoperative radiotherapy or chemotherapy. A total of 221 patients met the criteria. Immunohistochemical staining was used to count the CD8+ T cells in tumor center and invasive margin in the paraffin slides. Meanwhile the relative expression of CD8B gene in 22 fresh freeze samples of colorectal cancer was detected. Then the correlation of the expression with CD8+T cell density was examined. The patients were divided into high and low infiltration groups according to the level of CD8+T cells. Log-rank test was applied to compare the overall survival of the two groups of patients, and Cox regression analysis was used to adjust the prognostic significance of CD8+T cell infiltration. Results: There were 118 males and 103 females. In 221 slides, CD8+T cells infiltrating in invasive margin were more than those in tumor center [median (range): 37(0-141) / field vs. 14(0-106) / field, Z=-11.985, P<0.001], and the number of CD8+T cell in the tumor center was positively correlated with those in invasive margin (r=0.610, P<0.001). The number of CD8+ T cell in tumor center was positively correlated with the relative expression of CD8B gene (r=0.524, P=0.012). Survival analysis showed that the overall survival of the high infiltration group was better than that of the low infiltration group both in tumor center and invasive margin (median survival: 84.1 months vs. 73.5 months, P<0.001; 84.2 months vs. 75.9 months, P=0.002). Cox regression analysis revealed that high CD8+T cell infiltration in tumor center was an independent protective factor of overall survival (HR=0.369, 95% CI: 0.168-0.812, P=0.013). Conclusions: The infiltration level of CD8+T cells in tumor center is lower than that in invasive margin, and they are positively correlated. The level of CD8+ T cell infiltration in tumor center is related to overall survival and can be used as a potential pronostic marker.