IL18BP is a potential soluble immune checkpoint in cancer. A, Schematic depiction of IL18BP identification process as a potential soluble immune checkpoint. B, Representative example in human tumor associated macrophages (TAM) from lung adenocarcinoma versus alveolar macrophages (AM) from adjacent nontumor tissue (GSE162669) showing IL18BP expression in the two populations in BoxPlot (3 patients, for each three replicates). C, IL18BP expression following immune checkpoint blockade treatment in triple negative breast cancer (anti PD-1, EGAD00001006608_02), melanoma (anti PD-1 + anti CTLA-4, GSE91061), and basal cell carcinoma (anti PD-1, GSE123814). Statistical analysis was preformed using Wilcoxon signed-rank test. Data are shown in BoxPlot, patient sample numbers indicated below. D, scRNA analysis of tumor-infiltrating myeloid cells across indications showing IL18BP expression in myeloid populations in the TME compared with peripheral blood (PBMC). E, IL18BP expression in tumor-derived supernatants from individual patients across indications (n = 76). Tumor biopsies were collected from patients with cancer and dissociated; supernatants were collected and analyzed for IL18BP expression using ELISA assay. Each dot represents an individual sample. The median is depicted by a short black line. In BoxPlots, the bottom of the box indicates the first quartile (Q1), the 25th percentile of the data, and the top of the box indicates the third quartile (Q3), the 75th percentile; the line indicates the median. Whiskers extend to the smallest and largest values within 1.5 times the IQR from the first and third quartiles, respectively.