Abstract 937: Quantitative assessment of CD200 and CD200R expression in lung cancer
Authors: Vathiotis Ioannis A. , MacNeil Tyler , Zugazagoitia Jon , Martinez-Morilla Sandra , Ahmed Fahad , Syrigos Konstantinos N. , Gruver Aaron M. , Driscoll Kyla , Rimm David L. 
Published: September 2020

Abstract
Background: CD200 is a membrane-bound glycoprotein expressed on normal tissue, tumor and immune cells. The interaction of CD200 with its receptor leads to attenuation of the inflammatory process, resulting in tumor cell mediated immune suppression. CD200 has been characterized in hematologic malignancies and consists of an independent negative prognostic factor for chronic lymphocytic leukemia, acute myeloid leukemia and multiple myeloma patients. Here we assess both CD200 and CD200R expression in lung cancer and evaluate its association with clinicopathologic characteristics, mutation status, outcome and PD-L1 expression.
Methods: We used quantitative multiplexed immunofluorescence (QIF) to measure the expression of CD200 and CD200R in 287 non-small cell lung cancer (NSCLC) patients and 30 patients with large cell neuroendocrine carcinomas (LCNEC) of the lung. We performed target measurement with tyramide-based QIF panels and analyzed the data using the PM2000 microscope and AQUA software. Targets were measured in cytokeratin-positive (CK+) tumor compartment and cytokeratin-negative (CK-) stromal compartment.
Results: CD200 tumor positivity was found in 29.7% of NSCLC patients and 33.3% of LCNEC patients. CD200 demonstrated notable intratumoral heterogeneity (R2=0.09-0.31 between different TMA blocks versus 0.46-0.60 for CD200R). CD200R was expressed in immune cells in 25% of NSCLC and 41.3% of LCNEC patients. While CD200R is predominantly expressed in immune cells, rare tumor cell staining was seen in a highly heterogeneous pattern. CD200R expression in the stromal compartment was significantly higher in patients with squamous differentiation (p&lt;0.0001). Neither CD200 nor CD200R were associated with other clinicopathologic characteristics or mutation status. Both CD200 and CD200R were not prognostic for disease-free or overall survival in NSCLC. Since these biomarkers are associated with immune modulation, both markers were assessed for correlation with PD-L1. CD200 showed moderate correlation with PD-L1 (R2=0.28 in the CK+ compartment and 0.40 in the CK- compartment); CD200R was less correlated with PD-L1 (R2=0.07 in the CK+ compartment and 0.10 in the CK- compartment).
Conclusions: CD200 and CD200R pathway represents a novel immune checkpoint, frequently expressed in lung cancer patients. Co-expression patterns of CD200 and CD200R with PD-L1 suggest a potential role for targeting this pathway alone or in combination with PD-1/PD-L1 axis inhibitors.
Citation Format: Ioannis A. Vathiotis, Tyler MacNeil, Jon Zugazagoitia, Sandra Martinez-Morilla, Fahad Ahmed, Konstantinos N. Syrigos, Aaron M. Gruver, Kyla Driscoll, David L. Rimm. Quantitative assessment of CD200 and CD200R expression in lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 937.