Yun Fan, Lulu Miao, Yanjun Xu, Zhiyu Huang,Lei Gong

HangZhou Zhejiang CancerHospitalchemotherapy department

Objective: Blockingthe interaction between the programmed cell death (PD)-1 proteinand one of itsligands, PD-L1, has been reported to have impressive antitumor responses. PD-L1interaction is a major pathway often hijacked by tumors tosuppress immunecontrol. Studies on the roles of PD-L1 in non-small cell lungcancer (NSCLC) arecontroversial, but its roles in small cell lung cancer(SCLC) are rare andunclear. Moreover, MET/HGF axis seems to be the other oneof the most aberrantsignaling pathways in SCLC. The aim of our study was toinvestigate theexpression and prognostic roles of PD-L1 and cell ular-mesenchymal toepithelial transition factor (c-MET) in SCLC. Method: Theexpression of PD-L1 and c-MET were evaluated by immunohistochemical analysis in83 specimens of SCLC, including 47 limited disease (LD) and 36 extensivedisease(ED). Tumors with PD-L1 staining inover 5% of tumor cells were scored aspositive for PD-L1 expression. Tumors with c-MET strong stainingin at least 10%or weak to moderate staining in at least 40% of tumor cellswere scored aspositive for c-MET expression. Survival analysis was performedusing theKaplan-Meier method. Result: Thepositive rate of PD-L1 and c-MET in SCLC specimens were 51.8% and 25.3%respectively. The higher expression level of PD-L1 in tumor specimens was significantlycorrelated with a limited disease (LD) stage (P=0.004), a normalserumLDH level (P=0.031), and a normal NSE level (P=0.005). Noassociation was found between the expression level of c-MET and PD-L1, or c-METexpression with the other clinical characteristics of SCLC patients. SCLCpatients with PD-L1-positive tumors showed significantly longer overallsurvival (OS) than those with PD-L1-negative (median OS, 17.0 vs 9.0, P=0.018).SCLC patients with positive c-MET expression showed a trend of shorter overallsurvival (12.0 vs15.0, P=0.186). But sub-analysis of Limited disease(LD)-stage patients showed that the c-MET negative group had a longer OS (25.0vs 14.0; P=0.011). Multivariate analyses revealed that LD stage, goodperformance status butexcept for PD-L1 or c-MET immunoreactivity wereindependently predictive ofbetter OS. Conclusion：Inpatients with SCLC, expression of PD-L1 was positively correlated witha LDstage and better OS, but was not an independently predictive factor of outcome.High expression level of c-MET revealed a trend of worse outcome. It wasassociated with poor prognosis especially in LD-Stage patients.

Key Words：PD L1  cMET  small cell lung cancer