EP1.12-08 Programmed Death-Ligand 1 and Human Leukocyte Antigen Class I Expression in Various Neuroendocrine Tumors of the Lung

Abstract

Pulmonary neuroendocrine tumors (PNETs) encompass a broad spectrum of tumors including typical carcinoid (TC) and atypical carcinoid (AC) tumors, small cell lung carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC) with important pathological, biological and clinical differences. Recently, FDA grants Atezolizumab regimen for use in combination with carboplatin and etoposide for the frontline treatment of patients with extensive stage SCLC. The aim of this study was to investigate Programmed death-ligand 1(PD-L1) and Human leukocyte antigen (HLA) class I expression patterns in PNETs. PD-L1 and HLA class I expression was evaluated by immunohistochemistry in a total of 37 resected lung neuroendocrine tumors using tissue microarray. Correlations between the expression of HLA class I/PD-L1 and clinicopathologic features and prognostic significance were analyzed. Of the 37 patients enrolled in this study, 32 patients (86.5%) were male and the median age was 66 years (range, 35–81 years), and 28 patients (75.6%) were current or ex-smokers. The pathologic stage (AJCC 8th) in the patients at presentation was IA(including IA1, IA2, IA3) in 11 patients (24.3%), IB in 4 patients (10.8%), IIA in 1 patients (2.7%), IIB in 4 patients (10.8%), IIIA in 10 patients (27.0%), IIIB in 4 patients (10.8%), and IVA in 1 patients (2.7%). Histologically, 6 patients (16.2%) were diagnosed TC, 5 patients (13.5%) with AC, 9 patients (24.3%) with SCLC, and 17 patients (45.9%) with LCNEC. Positive PD-L1 expression in tumor cells was 29.7% (11/37, 1% cut-off), and the numbers (proportions) of positive PD-L1 expression according to histologic subtypes were as follows; TC/AC/SCLC/LCNEC, 2(33.3%)/2(40.0%)/1(11.1%)/6(35.2%). HLA class I expression was reduced in 86.5% (32/37). The numbers (proportions) of reduced HLA class I expression according to histologic subtypes were as follows; TC/AC/SCLC/LCNEC, 5(83.3%)/5(100%)/8(88.9%)/14(82.4%). In survival analysis, (median overall survival (OS); 56 months) there was no significant difference in OS according to PD-L1 and HLA class I expression status. However, two cases with HLA(+)/PD-L1(+) showed more unfavorable survival curves and three cases with HLA(+)/PD-L1(-) showed a tendency of more favorable clinical course. Lung NETs shows frequent HLA class I reduction and variable PD-L1 expression. Although this is a preliminary study including small number of NETs, the finding that NETs with HLA(+)/PD-L1(-) showed favorable clinical course suggests immune microenvironment might be one of the important biomarker for NETs of the lung.