Abstract 3636: The immune checkpoint, HVEM, is associated with PDL1 expression in lung cancer cell lines

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Abstract Background: Herpes Virus Entry Mediator (HVEM) is an important immune checkpoint in cancer recognition. HVEM expressed on tumor cell membranes activates immune cell signaling pathways leading to either inhibition of activity (BTLA) or activation of immune activity (LIGHT). This study is to investigate the prevalence of HVEM expression and its association with PDL1 expression in cell lines and patient tumor tissue.Methods: A TMA of 53 characterized NSCLC, 48 SCLC cell lines and 35 malignant tumors were evaluated for HVEM and PD-L1 expression. The IHC assay for HVEM was Dako Link48 autostainer using a polyclonal antibody from R&D Systems(AF356). PD-L1 IHC was performed on the Dako Link48 autostainer using the PD-L1 22C3 pharmDx kit. Scoring HVEM employed the H-score system while for PD-L1 the tumor proportion score (TPS) was used.Results: IHC HVEM staining was optimized and demonstrated membranous staining with little or no cytoplasmic or nuclear staining. HVEM expression in the NSCLC and SCLC cell lines and malignant tumor TMA revealed a positive H-score more than 1 was 45.3%, 58.3% and 82.9% respectively. In comparison, PDL1 TPS expression of more than 1% was in 59.2%, 16.67% and 45.71% in NSCLC, SCLC cell lines and malignant tumor respectively. A significant correlation of HVEM with PDL1 expression was found in the NSCLC cell lines (r=0.518, p<0.001), while there was no significant association of HVEM with PDL1 expression in the small cell line cohort (r=0.059, p=0.688). Conclusion: HVEM expression was found to be higher in SCLC cell lines as compared to NSCLC cell lines and substantially greater in the general malignant tumor tissues. HVEM expression is associated with PD-L1 expression in NSCLC cell lines but not in SCLC cell lines. This data suggests a potential benefit of combined PD-L1 and HVEM blockade in patients with NSCLC to improve the efficacy of immune-therapy. Table 1. HVEM Expression in the studyH score01-100101-200201-300NSCLC Cell lines(n=53)29 (54.72%)23 (43.4%)1 (1.8%)0SCLC Cell lines(n=48)20 (41.67%)26 (54.17%)2 (4.17%)0Malignant TMA n=356 (17.14%)16 (45.71%)9 (25.71%)4 (11.43%) Citation Format: Shengxiang Ren, Nadav Amar, Hui YU, Christopher Rivard, Kim Ellison, Leslie Rozeboom, Fred R. Hirsch. The immune checkpoint, HVEM, is associated with PDL1 expression in lung cancer cell lines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3636.