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摘要
Objective: To explore the role of the combination index of CD8+T cell count and programmed cell death-ligand 1 (PD-L1) mRNA expression level in predicting the efficacy of mismatch repair-proficient (pMMR) colorectal cancer after radical surgery and the short-term efficacy of immunotherapy. Methods: We analyzed the pathological tissues from Harbin Medical University Cancer Hospital, including 257 colorectal cancer patients after radical resection during February 12, 2013 to March 31, 2014 and 38 patients with advanced pMMR colorectal cancer after anti-programmed cell death protein-1(PD-1) treatment during January 7, 2019 to December 22, 2020. The count of CD8+T cell and level of PD-L1 mRNA in pathological tissues were detected by immunohistochemical staining and in situ hybridization, respectively.Meanwhile, survival analysis and efficacy evaluation were performed to determine whether the combination index could predict the long-term survival of patients with pMMR colorectal cancer after radical resection and the short-term efficacy of anti-PD-1 therapy (monotherapy or combination therapy) in patients with pMMR colorectal cancer.Kaplan-meier method was used to plot survival curve, and univariate Cox proportional risk model was used to determine whether CD8+T cell abundance was correlated with survival.Fisher's exact test was used to examine the relationship between negative and positive groups of combination index and objective response rate or disease control rate. Results: PD-L1 mRNA expression level was significantly associated with mismatch repair status in patients with colorectal cancer, P=0.045.PD-L1 mRNA expression was positively correlated with overall survival (OS) in patients with pMMR colorectal cancer after radical resection, HR=0.304, 95%CI was 0.145-0.639, P=0.001; but it was not associated with prognosis in patients with dMMR colorectal cancer, HR=1.881, 95%CI was 0.505-7.007, P=0.338. There was relevance between the expression intensity of PD-L1 mRNA and the invasion degree of CD8+T cell in tumor, P=0.005.ROC curve and univariate analysis showed that patients with CD8+T cell density greater than or equal to 21.8 HPF-1 had better OS, HR=0.400, 95%CI was 0.182-0.879, P=0.018. The critical condition for the combination index of CD8+T cell and PD-L1 mRNA was set as CD8+T cell≥21.8 HPF-1 and PD-L1 mRNA(+++).Patients meeting the combination index were classified as applicable group, whose OS were better than those in non-applicable group, HR=0.318, 95%CI was 0.100-1.014, P=0.040.Retrospective analysis showed that patients with pMMR colorectal cancer meeting the above criteria had higher objective response rate (5/9 vs 2/29, P=0.041) and disease control rate (8/9 vs 8/29, P=0.002) after anti-PD-1 therapy (4 cases of monotherapy and 34 cases of combination therapy). Conclusions: Patients with pMMR colorectal cancer whose combination index of CD8+T cell and PD-L1 mRNA match CD8+T cell≥21.8 HPF-1 and PD-L1 mRNA(+++) have a better survival advantage after radical resection and are more potential to benefit from anti-PD-1 combination therapy. ? 2022, Editorial Board of Chinese Journal of Cancer Prevention and Treatment. All right reserved.
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