15P Serum immune checkpoint biomarkers as predictors of response to anti-PD-1/PD-L1 treatment in non-small cell lung cancer (NSCLC) patients

Abstract

There is limited data on the predictive biomarkers of response to immune checkpoint blockade (ICB) treatment of non-small cell lung cancer (NSCLC) patients. The main aim of this prospective study is to understand the utility of pre-treatment soluble immune checkpoint and tumor markers as early predictors of response in locally advanced/metastatic NSCLC patients treated with ICBs. The study was conducted at the National Center for Cancer Care and Research (NCCCR), HMC, Qatar. A total of 26 patients on anti-PD-1/PDL-1 treatment were enrolled, and pre-treatment blood samples were collected. Multiplex Magnetic Bead Panel kits were utilized to measure concentrations of soluble immune checkpoint and tumor markers including BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PDL-1, PDL-2, TIM-3, CD28, CD80, 4-1BB, CD27, CTLA-4, ICOS Ligand, CD276, VISTA, B7-H6; CD47 (IAP), BLAST-1, Galectin-9, TIMD-4; OX40, S100A8/A9, E-cadherin, MICB, Nectin 2, NTSE, PVR, Singlec 7, Singlec 9,CEA, CA-19-9, CA-125 CYFRA21-1 and CA-15-3. Mann-Whitney test was used to evaluate difference in medians in responders and non-responders. Response to treatment was assessed 4 months after initiation of treatment via PET CT imaging data. Clinical response to ICB treatment was determined based on RECIST criteria and PET CT imaging data. 12/26 (46%) patients showed clinical response to the treatment while 14/26 (54%) were identified as non-responders. Interestingly, in clinically responding patients, significant upregulation of the immune inhibitory soluble programmed death-ligand 1 (sPD-L1) molecule (<0.002**) and the immune stimulatory biomarkers glucocorticoid-induced TNFR-related protein (GITR) (<0.0005***), and Herpes virus entry mediator (HVEM) (<0.006**) were recorded. However, non-responding patients showed significant upregulation of 3 important immune suppressive biomarkers; T-cell immunoglobulin and mucin domain containing 4 (TIMD-4) (p<0.0361*), Nectin 2 (p<0.0310*) and the carcinoembryonic antigen (CEA) tumor marker (p<0.0484*). The study shows that soluble immune suppressive/stimulatory biomarkers can serve as plausible early biomarkers of response to ICB treatment.