166 High CTLA-4 transcriptomic expression correlates with high expression of other checkpoints and with outcome on immune checkpoint inhibitors

BackgroundCTLA-4 is a membrane glycoprotein expressed by activated effector T cells that impedes the immune system’s antitumor response. There are two FDA-approved anti-CTLA-4 agents—ipilimumab and tremelimumab, both used together with anti-PD-1/PDL1 agents.MethodsWe evaluated RNA expression levels (OmniSeq (https://www.omniseq.com)) and clinical correlates of CTLA-4 and other immune checkpoints in 514 tumors. A reference population (735 tumors; 35 histologies) was used to normalize transcript abundance to internal housekeeping gene profiles and rank transcript abundance (0–100 percentile). Altogether, 217 patients (42.2% of 514) received immune checkpoint inhibitor (ICI) therapy. Kaplan Meier was utilized for progression-free-survival (PFS) and overall survival (OS) analyses.ResultsThe most common tumor types were colorectal (140/514, 27%), pancreatic (55/514, 11%), breast (49/514,10%), and ovarian cancer (43/514, 8%). Overall, 87 of 514 tumors (16.9%) had high CTLA-4 transcript expression (≥75 percentile). Cancers with the greatest proportion of high CTLA-4 transcripts were cervical cancer (80% of patients), small intestine cancer (33.3%), and melanoma (33.3%). Across cancers, high CTLA-4 RNA was seen in 16.9% of tumors (87/514) and correlated with high PD-1, PD-L2, and LAG3 (but not with high PD-L1) expression (all p75 RNA percentile rank) versus moderate/low (