The Effects Of PD-1/PD-L1 Signal On Clinical Course And Prognosis Of MYC/BCL2 Double Expression Lymphoma

Objective:To investigate the correlation of programmed cell death1/programmed cell death ligand 1 pathway(PD1/PD-L1)with the overexpression of MYC and BCL2,analyse the expression characteristics of PD1 and PD-L1 in MYC/BCL2 double expression lymphoma(DEL);And explore the relationship between PD1/PD-L1 and clinicopathological features and overall survival time(OS)of DEL patients.Methods:A total of 90 cases of DLBCL tissue wax blocks from pathology department of guizhou medical university were enrolled in this study(January 2010—December 2017);The m RNA relative expressions of PD1 or PD-L1 were detected by real-time fluorescence quantitative PCR(RT-q PCR);The protein of PD1,MYC and BCL2 was detected by immunohistochemical staining(IHC),but the expressions of PD-L1 in tumor cells or in tumor microenvironment cells(m PD-L1)[Tumor-infiltrating lymphocytes(TILs)]were detected by double staining immunohistochemistry(D-IHC);MYC and BCL2 proteins were grouped according to their expression results(DEL and non-DEL group);The clinicopathological data were collected and followe-up was done;Finally,The experimental data were statistically analyzed.Results:1.The PD1 and PD-L1:In 90 cases,the average relative m RNA expression levels of PD1 and PD-L1 were respectively 1.369 and 1.102;PD1 positive rate was 32.22%(29/90);PD-L1 positive rate of tumor cells(PD-L1~+)was 24.44%(22/90),and PD-L1 positive rate of tumor microenvironment cells(m PD-L1~+)was28.89%(26/90);The PD-L1 protein expression was correlated with the the protein positive rate of MYC and BCL2(P<0.05),but the expression of PD1 protein was not correlated with them(P>0.05).The contrast of DEL cases were with non-DEL cases:The expressions of PD-L1 m RNA,the protein of PD-L1 and m PD-L1 were statistically different between DEL and non-DEL groups,and significantly increased in the DEL group(P<0.05);But the expression of PD1 m RNA and protein showed no significant difference between the above groups(P=0.066,0.053).2.The relationship between PD1/PD-L1 and the clinicopathological features in DEL:There were differences in the expression of PD-L1 protein in different B symptoms and IPI assessment groups,that is,patients with PD-L1 protein in this type of lymphoma were prone to B symptoms and had high IPI scores(P<0.05);Whereas,it were no difference among different groups of gender,age,Hans typing,clinical stage,symptom B,IPI score,LDH,?2-MG that m RNA of PD1 and PD-L1 expression(P>0.05),and the protein of PD1 and m PD-L1 positive expression the same is true(P>0.05).3.survival analysis:Kaplan-meier showed that the positive expressions of PD-L1 and m PD-L1proteins were related to the patients'OS—the positive expressions of PD-L1 and m PD-L1 had relatively short in 22 patients with DEL(P<0.05);However,between the expression of PD1 protein and OS of the patients was unsignificant correlation(P=0.711).Conclusion:Both tumor cells and tumor microenvironment cells positively expressed PD-L1 in some DLBCL cases.PD-L1 was positively correlated with the positive expression of MYC and BCL2,And the m RNA and protein of PD-L1 were both up-regulated,which suggests that PD-L1 may play an important role in the onset or progression in DEL.In addition,The positive expression of PD-L1 and m PD-L1proteins is related to shorter OS of patients,which may be a related factor in the poor prognosis evaluation of DEL patients.