The Expressions And Clinical Significance Of PD-L1 In Diffuse Large B Cell Lymphomas

Background: Diffuse large B-cell lymphoma(DLBCL)is the most common subtype of non Hodgkin lymphoma,ABC/non-GCB subtype lymphoma is more aggressive than GCB type lymphoma,with worse prognosis,and often occurs in chemotherapy resistance.When the MYC and BCL2 gene translocations,we called it double-hit lymphoma,if the corresponding protein co-expression,we called it double expression,both types of lymphoma are often with higher degree of malignancy than those common patients.Although the use of standard R-CHOP chemoimmunotherapy has the potential to cure,there are still a large number of patients occurs with recurrence and refractory,especially those double-hit/double expression of ABC/non-GCB patients.Targeted therapy based on molecular pathways may be considered for this part of the patient,and previous studies include the use of BET inhibitors,BCL2 inhibitors and BCL6 inhibitors,which are still in preclinical phase.Recent studies have shown that PD-1/PD-L1 signaling is widely expressed in hematological malignancies.Programmed cell death ligand 1(PD-L1)is a cell surface glycoprotein that regulates the cellular immune response and serves as a targetable immune checkpoint molecule.The use of PD-L1 inhibitors has made a major breakthrough in solid tumors,and the research of PD-L1 in hematological malignancies is also of extensively focused.Aims: To investigate the clinicopathological characteristics of programmed cell death ligand 1(PD-L1)expression of diffuse large B cell lymphoma(DLBCL).and to investigate the correlation between the expression of PD-L1 in tumor tissue of DLBCL patients and the clinical and pathological features of DLBCL patients.The relationship between the expression of PD-L1 in tumor tissue of DLBCL patients and the curative effect of chemotherapy was also analyzed,Combined with foreign related research to explore the clinical significance of the results.Methods: The clinical and pathological features,treatment status and survival status of 50 patients with DLBCL who were treated in the Second hospital of Dalian Medical university from May 2014 to May 2016 were retrospectively collected.After screening by our hospital pathology(except for puncture tissue).PD-L1 immunohistochemical staining was performed in the rest 31 untreated DLBCL tissue samples to evaluate the expression of PD-L1 in tumor cells and tumor-infiltrating immune cells(mainly macrophages).We use SPSS22.0 to analyze whether the expression of PD-L1 was correlated with the clinical and pathological characteristics of patients with DLBCL.and whether the expression of PD-L1 was related to the efficacy of patients with chemotherapy and progression-free survival.Results: There were 11 cases(35.5%)of GCB in 31 cases of DLBCL,20 cases(64.5%)of non-GCB;7 cases(22.6%)with B symptoms,24 cases(77.4%)without B symptoms;There were 12 double expression patients(38.7%),and 19 patients were not double expression(61.3%);27 patients(12.9%)with Epstein-Barr virus infection,27 patients(87.1%)without EBV infection.The expression of PD-L1 was positive in 16 patients(51.6%)in 31 patients with DLBCL.The positive rate of PD-L1 in patients with B symptoms group(85.7%)was higher than group without B symptoms(41.7%),and the positive rate of PD-L1(100%)in Epstein-Barr virus group was higher than that in group without EBV.The expression of PD-L1 was significantly correlated with B symptom(P = 0.040)and EB virus infection(P = 0.038).The expression of PD-L1 in non-GCB(non-germinal center)lymphoma was higher than that in GCB(65.0% vs 27.2%,P = 0.044).The expression of PD-L1 was higher in the double expression group than in the common group(75.0% vs 36.8%,P = 0.038).There were no significant correlation between the expression of PD-L1 with Age,Sex,Ann Arbor stage,Primary site,ECOG score,Ki67,serum LDH levels of DLBCLs.After two cycles of CHOP or R-CHOP treatments,except 15 cases can not evaluate the efficacy of patients(no tumor state),there were 1 patients got uncertain complete remission,4 patients got partial remission,the response rate of PD-L1 negetive group(RR=5/7),there were 4 patients got partial remission,the response rate of PD-L1 positive group(RR=4/9),the response rate(RR)was higher in PD-L1 negative group than that in positive group(71.4% vs 44.4%,?2=1.165,P>0.05),The difference was not statistically significant,and the PD-L1 expression was not considered to be negatively correlated with the therapeutic effect.The median progression-free survival was 290 days in these patients,with a median progression-free survival of 416 days in the PD-L1 negative group and 280 days in the PD-L1 positive group.Conclusions: 1.The expression of PD-L1 was significantly correlated with B symptom and EBV infection,and had no significant correlation with other clinical and pathological features.2.The PFS of patients with negative expression of PD-L1 was longer than that of PD-L1 positive group.3.The expression of PD-L1 in non-GCB type lymphoma was higher than that in GCB type.The expression of PD-L1 in the double expression(DEL)group was higher than that in non-double expression group,especially those with EBV-infected non-GCB patients.