Abstract 3151: Quantitative measurement of Siglec-15 expression in non-small cell lung cancer and its association with PD-L1, B7-H4 and tumor infiltrating lymphocytes

Introduction: Siglecs are sialic acid-binding transmembrane receptors that regulate the functions of innate and adaptive immune system through the recognition of glycan ligands. Siglec-15 has been recently described as an immune suppressive molecule that shares molecular structure with PD-L1, but its role in NSCLC is still unknown. In this study, we determined Siglec-15 expression in three retrospective NSCLC cohorts and evaluated its association with mutation status, major clinicopathologic characteristics and survival. Experimental procedures: We used multiplexed automated quantitative immunofluorescence (QIF) to develop a validated assay for Siglec-15 measurement and used it to assess Siglec-15 expression and its association to major clinicopathologic variables and survival in three NSCLC cohorts of over 600 patients. Additionally, we investigated the correlation of Siglec-15 expression with tumor-infiltrating lymphocytes, PD-L1, B7-H3 and B7-H4 tumor expression. Results: In our study, Siglec-15 tumor positivity was found in 12.5%, 13.7% and 22.8% of NSCLC cohort patients. Siglec-15 expression was higher in EGFR mutant and EGFR/KRAS wild type tumors compared to KRAS mutants but was not associated with any other major clinicopathological characteristics. Siglec-15 followed a mutually exclusive pattern of expression with PD-L1, B7-H3 and B7-H4 (co-expression in 3.1%, 13.2% and 7.7% of the patients respectively), while high levels were not correlated with lymphocyte infiltration or T-cell activation, suggesting a different upregulation mechanism not mediated by IFN-gamma. Conclusions: Siglec-15 is a protein expressed with high frequency in NSCLC. Co-expression of Siglec-15 with PD-L1, B7-H3 and B7-H4 is relatively rare, suggesting that Siglec-15 has distinct and non-redundant features compared to other B7 family members. Citation Format: Maria Toki, Jon Zugazagoitia, Mehmet Altan, Linda Liu, Nikita Mani, Yuting Liu, Konstantinos Syrigos, Lieping Chen, Solomon Langermann, Roy Herbst, David Rimm. Quantitative measurement of Siglec-15 expression in non-small cell lung cancer and its association with PD-L1, B7-H4 and tumor infiltrating lymphocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3151.