Abstract 1762A: CD200 and CD200R1 expressions and their prognostic roles in patients with non-small cell lung cancer
Authors: Yoshimura Katsuhiro , Suzuki Yuzo , Inoue Yusuke , Karayama Masato , Iwashita Yuji , Kahyo Tomoaki , Kawase Akikazu , Tanahashi Masayuki , Ogawa Hiroshi , Inui Naoki , Funai Kazuhito , Shinmura Kazuya , Suda Takafumi , Sugimura Haruhiko 
Published: August 2018

Abstract
Background: CD200 is a member of the immunoglobulin superfamily and is expressed in various cells. CD200 interacts its receptor CD200R, which is mainly expressed in myeloid lineage cells, and modulate cancer immune-microenvironments. High CD200 expressions in hematologic malignancies were associated with poor prognosis and a clinical trial of anti-CD200 antibody has already conducted. However the role of CD200/CD200R signaling in solid cancers including non-small-cell lung cancer (NSCLC) have yet to be elucidated.
Methods: We evaluated CD200 and CD200R1 protein expression using immunohistochemically stained tissue microarrays containing 653 resected NSCLC specimens. The tumor expression levels were assessed using the H-score method that ranged from 0 to 300. The stromal expression levels were also assessed semi-quantitatively. The cut-offs were determined using the minimum P-value method for overall survival (OS). The associations between their expression levels and clinicopathological data were retrospectively analyzed. In addition, we investigated CD200 and CD200R1 expressions among lung-cancer cell-lines. In vitro, endogenous immunorelated factor levels and cell proliferation changes were evaluated according to CD200 knockdown and CD200-Fc fusion protein administration.
Results: The median age of patients was 69.5 years old (23-88 years) and 444 (67.8%) patients were male. 444 (68.0%) patients were smoking history and 431 (66.0%) patients had adenocarcinoma. The median follow-up duration was 3.6 years. CD200 expression was mainly observed in tumoral area but not in stroma, whereas CD200R1 expression was observed in both tumoral and stromal area. CD200 and CD200R1 expressions were inversely correlated. Higher tumoral CD200 expression and lower stromal CD200R1 expression were significantly prominent in female, in never smokers, and in adenocarcinoma. CD200 expression was significantly associated with TTF-1 positivity and EGFR mutations. Higher tumoral CD200 expression was an independent favorable prognostic factor for NSCLC in multivariate Cox regression analyses for OS (hazard ratio (HR), 0.65; 95% confidence interval (CI), 0.45-0.94). In contrast, higher CD200R1 expressions in both tumor and stroma were poor prognostic indicators for OS (Log-rank, p=0.019 for tumor, and p&lt;0.001 for stroma). In vitro, we observed that both CD200 and also CD200R1 were expressed in several lung-cancer cell-lines. Treatment with CD200-Fc on PC9 did not change any cytokine levels. Knockdown of CD200 in H1299 did not show any effects on cell proliferations, but significantly decreased endogenous TNFα levels.
Conclusion: CD200R1 expression had poor prognostic capability in resected NSCLC. Inversely, CD200 expression was an independent favorable prognostic factor. CD200/CD200R axis was involved in patients' prognoses and would be a candidate of potent therapeutic target for NSCLC.
Citation Format: Katsuhiro Yoshimura, Yuzo Suzuki, Yusuke Inoue, Masato Karayama, Yuji Iwashita, Tomoaki Kahyo, Akikazu Kawase, Masayuki Tanahashi, Hiroshi Ogawa, Naoki Inui, Kazuhito Funai, Kazuya Shinmura, Takafumi Suda, Haruhiko Sugimura. CD200 and CD200R1 expressions and their prognostic roles in patients with non-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 1762A.