The Expression And Significance Of PD-L1,CD4⁺T,CD8⁺T Cell In Colorectal Cancer

Objective:To investigate the expression and clinical significance of programmed cell death ligand 1（PD-L1）,CD4⁺T cells and CD8⁺T cells in colorectal cancer（CRC）.Methods: We used bioinformatics methods to analyze the correlation between the genes’ m RNA expression level of PD-L1,CD8A and CD4 in 275 CRC samples and the expression level of PD-L1 gene that correlated with the immune infiltration of CD8⁺T cells,CD4⁺T cells and macrophages in the expression of tumor microenvironment（TME）of CRC.Immunohistochemical staining was used to detect the expression of PD-L1,CD4⁺T cells and CD8⁺T cells in the normal group,high microsatellite and instability（MSI-H）group and metastasis group.Kaplan-meier method was used for survival analysis.Results:（1）PD-L1,CD8A and CD4 gene m RNA expression levels in CRC tumor tissue samples were correlated,and PD-L1 was strongly correlated with CD8A（r=0.73）while PD-L1 was moderately correlated with CD4（r=0.68）,and CD8A was moderately correlated with CD4（r=0.68）.PD-L1,CD8A and CD4 genes had no independent effect on the prognosis of CRC.（2）In colon and rectal cancers,PD-L1 gene expression levels were positively correlated with CD8⁺T cells and macrophage infiltration.The positive rate of PD-L1 was 54.1%（46/85）in CRC group,50.0%（8/16）in MSI-H group,14.8%（4/27）in primary lesion and 11.1%（3/27）in metastatic lesion.Whether positive rates of PD-L1 of in primary or metastatic lesion were significantly lower than the CRC group and the MSI-H group（P < 0.05）.There’s no significant difference in PD-L1 positive rates between CRC group and MSI-H group（P > 0.05）.（3）The positive rate of PD-L1+CRC cells in CRC group was higher in the CD4⁺T cell high density group（65.9%,P < 0.05）and the CD8⁺T cell high density group（69.8%,P<0.05）.In CRC group,there’re low positive correlation between each pair of PD-L1,CD4⁺T cell invasion density and CD8⁺T cell invasion density.（4）In MSI-H group,the correlation between PD-L1 and the infiltrating density of CD4⁺T cells and CD8⁺T cells was not statistically significant.However,the positive rate of PD-L1+MSI-H group CRC cells was higher in age ≥60 years group（75.0%,P <0.05）.（5）In the metastatic group,the correlation between the expression of PD-L1 and the infiltrating density of CD4⁺T cells and CD8⁺T cells in the primary lesions was positive.（6）The expression of PD-L1 and the infiltrating density of CD4⁺T cells and CD8⁺T cells in the metastatic lesions were positive linked.（7）In the metastatic CRC group,median survival time was 19 months,and survival time was negatively associated with vascular infiltration and primary CD4⁺T cell density infiltration.Patients with low density of CD8⁺T cell infiltration in distant CRC metastasis had better prognosis than those with high density of CD8⁺T cell infiltration in distant CRC metastasis.Conclusion: The expression levels of PD-L1,CD8 and CD4 were correlated in CRC group.TILs expression can be included in combination with PD-L1 expression to evaluate the expected benefit of CRC patients receiving anti-PD-1 /PD-L1 immunization.However,PD-L1 between the primary and metastatic lesion was basically unrelated to TILs infiltration,and only PD-L1 in the metastatic lesion was correlated with the infiltration density of CD8⁺T cells in the primary lesion.The high expression of PD-L1 in MSI-H type CRC has positive significance for survival status.The effect of TILs on prognosis of metastatic CRC is still controversial.PD-L1 may affect the progression of CRC by regulating immune cell infiltration in TME.