Abstract 3637: Expression of an immune checkpoint- Poliovirus Receptor (PVR) in small cell lung cancer
Authors: Hui Yu, Camilla Koczara, Andrzej Badzio, Dexiang Gao, Christopher J. Rivard, Kim Ellison, Kenichi Suda, Shengxiang Ren, Charles Caldwell, Kristine A. Brovsky, Leslie Rozeboom, Fred R. Hirsch
Journal: Cancer Research (2018)

Abstract Background: Although immunotherapy has renewed hopes for the improved treatment of SCLC, the “classical” PD-1/PD-L1 pathway is not commonly expressed in SCLC. PVR (CD155) is expressed at low levels in a number of cell types of epithelial origin and is overexpressed in various carcinomas with epithelial and neurological origins, including colorectal carcinoma, breast carcinoma, neuroblastoma and glioblastoma. In this study, we evaluated the expression of PVR in SCLC cell lines and a cohort of patient tumors with association to clinical characteristics. Methods: Immunohistochemistry (IHC) was performed to evaluate PVR protein expression in 39 SCLC cell lines as well as a cohort of 77 resected tumors from SCLC patients with clinical data using a monoclonal PVR antibody (D8A5G,Cell Signaling, MA). Scoring data was generated using both the H-score and tumor proportion score (TPS) systems. PVR expression was correlated with characteristics of both the cell lines and the clinical cohort. Results: The SCLC cell lines were evaluated by the H-score system only. A total of 39 SCLC cell lines in a TMA were evaluated in which 37 cell lines (95%, 37/39) demonstrated PVR staining &amp;gt; 0 and 85% of the cell lines showed positive staining with an arbitrary H-score cutoff of 50. PVR expression was higher in cell lines established from pre-treated SCLC patients as compared to those established from treatment-naïve patients (P=0.037). There was no correlation between PVR expression and cell line growth as suspension versus adherent cells. In the SCLC patient cohort, PVR expression was found to be predominantly on the membrane of tumor cells, with minimal expression observed on immune cells in the tumor microenvironment. PVR expression in the SCLC patient cohort was 82% with H-score cutoff of ≥ 50. SCLC patients with positive PVR expression demonstrated a poorer prognosis, however the difference was not statistically significant (p=0.05). Positive PVR expression was also correlated with advanced stage (P=0.0073) and higher in male patients (P=0.04). With a TPS score system (cutoff of ≥ 50%) the prevalence of PVR expression is 79%. Using the TPS system, higher PVR expression was associated with poor prognosis and advanced stage (P=0.046, and P=0.045). PVR expression also as evaluated with the TPS score system was correlated with large tumor diameter (P=0.043) and older age of patients (P=0.046). Conclusion: PVR was broadly expressed in SCLC cell lines and tumor tissues. High PVR expression was associated with poor prognosis, advanced tumor stage, large tumor diameter, and advanced age of patients. We also found that PVR expression may correlate with chemotherapy treatment history in SCLC cell lines. These data suggest that the PVR-TIGIT pathway may be a promising target for immunotherapy in SCLC. Citation Format: Hui Yu, Camilla Koczara, Andrzej Badzio, Dexiang Gao, Christopher J. Rivard, Kim Ellison, Kenichi Suda, Shengxiang Ren, Charles Caldwell, Kristine A. Brovsky, Leslie Rozeboom, Fred R. Hirsch. Expression of an immune checkpoint- Poliovirus Receptor (PVR) in small cell lung cancer [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 3637.