Abstract 404: Prognostic value of soluble and cell surface immune-checkpoint molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/-L1 immunotherapy
Authors: Imad Tarhoni, Mary Jo Fidler, Ibtihaj Fughhi, Connor Wakefield, Revathi Kollipara, Maneet Multani, Marta Batus, Sanjib Basu, Wen-Rong Lie, Donna Russell, Jeffrey Martinson, Alan L. Landay, Timothy M. Kuzel, Philip Bonomi, Jeffrey A. Borgia
Journal: Cancer Research (2019)

Abstract Current methods to stratify immunotherapy candidates, including PD-L1 expression and tumor mutational burden (TMB) profiling, have limitations that hamper their clinical value. This study explores the prognostic potential of soluble and cell-surface immune-checkpoint (IC) molecules as a means to improve treatment selection for NSCLC patients being considered for PD-1/-L1 blockade. Pretreatment sera from 111 cases of previously-treated advanced NSCLC receiving PD-1/L-1 targeting checkpoint inhibitors (nivolumab, atezolizumab, or pembrolizumab) were evaluated for 16 soluble IC molecules and immune regulators via the MILLIPLEX® MAP Human Immuno-Oncology Checkpoint Protein Panel (MilliporeSigma) using manufacturer-defined protocols. PBMCs from a subset of this cohort (n=28) were profiled on a LSRFortessa™ for cell-surface IC molecules. T-cell subsets (CD4,CD8) were analyzed for CD27\CD28, iCOS, PD-1, CTLA-4, TIM-3, TIGIT, LAG-3, GITR and PD-L1. NK cells (CD56\CD16) were analyzed for CD96, CD94, CD86, CD80, PD-1, CTLA-4, TIM-3, TIGIT, LAG-3 and PD-L1. Classical (CD14++\CD16-), intermediate (CD14++\CD16+) and non-classical (CD14dim\-\CD16++) monocyte subsets were analyzed for these identical markers. All statistical relationships were determined using the Log-Rank test in relation to overall survival (OS) and progression-free survival (PFS). Pearson correlations were calculated between the circulating and PBMCs levels of IC molecules. Sixteen soluble IC molecules were detectable in patient serum, with twelve of these being prognostic for OS, PFS, or both (see Table). In the 28 patients with PBMCs, a set of cell-surface molecules showed prognostic value, but had no apparent correlation to soluble molecules. These findings suggest that both soluble and cell-surface IC molecules may have promise for identifying advanced NSCLC patients that may benefit from anti-PD-1/-L1 immunotherapy. PFSOSp-valueHRp-valueHRSoluble moleculesBMI0.0030.790.0540.75Lymphocyte0.0040.700.0020.60NLR0.0051.69&amp;lt;0.0012.12BTLA0.0140.790.010.90CD270.0020.680.0170.80TIM30.0370.880.0280.93HVEM0.0040.620.0040.53GITR0.0010.003&amp;lt;0.0010.00LAG30.0400.820.030.72GITRL0.0140.100.0070.03PD10.0020.490.0030.34CTLA4&amp;lt;0.0010.180.0020.27CD800.0010.680.0020.67CD86&amp;lt;0.0010.63&amp;lt;0.0010.54iCOS0.0140.840.0470.90PBMCs - cell surface moleculesCD30.0520.660.110.65CD3-CD800.370.990.0051.45CD4-iCOS0.050.740.491.35CD8-CTLA40.020.660.21.34CD8-GITR0.0230.490.30.70CD8-TIGT0.020.630.370.78CD8-LAG30.0160.620.031.18CL-CD860.360.900.050.56CL-CD640.141.330.0151.89NC-CD640.0261.520.0021.74NC-PDL20.0382.840.351.52NC-TIM30.0032.070.041.19 Citation Format: Imad Tarhoni, Mary Jo Fidler, Ibtihaj Fughhi, Connor Wakefield, Revathi Kollipara, Maneet Multani, Marta Batus, Sanjib Basu, Wen-Rong Lie, Donna Russell, Jeffrey Martinson, Alan L. Landay, Timothy M. Kuzel, Philip Bonomi, Jeffrey A. Borgia. Prognostic value of soluble and cell surface immune-checkpoint molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/-L1 immunotherapy [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 404.