Abstract 1621: Comprehensive profiling of immune regulatory molecules in baseline sera from advanced stage NSCLC patients receiving anti-PD-1 and anti-PD-L1 immunotherapy: A prognostic potential
Authors: Tarhoni Imad , Moudgalya Hita , Basu Sanjib , Lie Wen_Rong , Pepin Danielle , Fidler Mary Jo , Batus Marta , Bonomi Philip , Borgia Jeffrey 
Published: July 2021

Abstract
Introduction: Immune checkpoint inhibitor (ICI) therapy has shown remarkable benefits in treating non-small-cell lung cancer (NSCLC). However, progress beyond PD-L1 expression has not yielded biomarkers that can better select responders to ICI. This study comprehensively evaluated the prognostic value of soluble immune checkpoints and immune regulators in previously treated lung cancer patients receiving anti PD-L1/PD1 single agents.
Method: We profiled 47 immune checkpoint molecules and regulatory molecules in baseline serum from 135 metastatic NSCLC patients receiving atezolizumab (n=40), pembrolizumab (n=32), durvalumab (n=10), or nivolumab (n=53) after failing frontline therapy. Immune checkpoints and regulators were evaluated via the MILLIPLEX® Human Immuno-Oncology Checkpoint Protein Panels 1 and 2 (MilliporeSigma) using manufacturer-defined protocols. All statistical relationships were determined using the Log-Rank test in relation to overall survival (OS) and progression-free survival (PFS).
Results: The study cohort consisted of 50% males, 72% caucasians, and histologically divided into 72% adenocarcinoma and 25% squamous cell. The median follow-up time was ten months from the time of ICI therapy commencement. The median PFS was 4.1 months, and overall survival was 13.1 months for the entire cohort. Twenty eight molecules were found to be significantly associated (p &lt;0.05) with progression free survival (PFS), out of which the baseline serum levels for circulating CD27, GITR, PD-1, CTLA-4, CD80, CD86, CD40L, B7-H2/ICOSL, E-Cadherin, FGL1/Hepassocin, Galectin-1, and Perforin showed the highest significance (all p-values &lt;0.01). Similarly, twenty-six of the profiled molecules were found to have significant association (p &lt;0.05) with overall survival (OS), with baseline serum levels of PD-1, CTLA-4, CD80, CD86, CD40L, B7-H2/ICOSL, E-Cadherin, FGL1/Hepassocin, Galectin-1, and Perforin being the most highly associated with OS (all p-values &lt;0.01).
Conclusion: We demonstrated the promising value of circulating immune checkpoints and immune regulatory molecules in precision immuno-oncology related to advanced-stage NSCLC. This work requires validation but, with further development, may have implications for single agent anti PD-L1/PD-1 treatment selection in the front-line setting.
Citation Format: Imad Tarhoni, Hita Moudgalya, Sanjib Basu, Wen_Rong Lie, Danielle Pepin, Mary Jo Fidler, Marta Batus, Philip Bonomi, Jeffrey Borgia. Comprehensive profiling of immune regulatory molecules in baseline sera from advanced stage NSCLC patients receiving anti-PD-1 and anti-PD-L1 immunotherapy: A prognostic potential [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1621.