Background: Co-signaling molecules PD-L1, B7-H3, and PD-1 play a key role in tumor immunology. However their expression has not been characterized in cSCC. Methods: Weretrospectively analyzed 70 cases of cSCC treated with surgical resection between 2012 and 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (PD-L1%) and B7-H3 (B7-H3%) (Abcam), density of peri and intratumoral CD8 T cells (CD8 density) and proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) (Abcam). Statistical analysis was performed using non-parametric Mann-Whitney test, chi-square test and Spearman’s rank correlation, Rs. Results: Of 70 cases, 45 were immunocompetent, 25 immunosuppressed (13 organ transplant, 8 HIV+, 4 other). Defining positive expression as > 5%, 26% of all tumors were positive for PD-L1, 85% for B7-H3, and 80% had CD8 T cells that co-expressed PD-1. Amongst immunocompetent patients, 27% of tumors were PD-L1 positive, 88% B7-H3 positive, and 80% had CD8 T cells that co-expressed PD-1. B7-H3% was significantly higher (Median 60% vs. 28%, p = 0.025) in immunocompetent vs. immunosuppressed patients, however there was no significant difference in PD-L1%, CD8 density, or CD8-PD-1%. When factoring in cause of immunosuppression, again only B7-H3% was significantly different between groups. Tumors from HIV+ patients lacked PD-L1 expression, had lower B7-H3% (Median 2.5% vs. 60%, p = 0.007), and higher CD8 density (Median 75% vs. 40%, p = 0.039) than tumors in immunocompetent patients. PD-L1% increased with increasing CD8 density (Rs = 0.31, p = 0.011) and CD8-PD-1% (Rs = 0.28 , p = 0.02). There was no correlation between B7-H3% and PD-L1%, CD8 density, or CD8-PD-1%, nor was there any correlation between tumor grade and these parameters. Conclusions: SCCs showed expression of PD-L1 and B7-H3, as well as PD-1 expression on peri- and intra-tumoral CD8 T cells. Tumor B7-H3 expression was significantly higher in immunocompetent vs. immunosuppressed patients, largely driven by very low expression in HIV+ patients.