Case-control study of PD-1, PD-L1 and B7-H3 expression in lung cancer (CA) patients (pts) with and without human immunodeficiency virus (HIV) infection.

Abstract

11606 Background: PD-1, PD-L1 and B7-H3 are co-signaling molecules involved in CA immunology. There are limited data on expression of these molecules in HIV-infected (HIV+) lung CA pts and these pts are routinely excluded from immunotherapy trials. Methods: We reviewed archived lung CA tissue samples from HIV+ cases (n = 13) and HIV-uninfected controls (n = 13) from 2001-2015. Cases and controls were matched by histology and stage. Baseline demographics were collected for all pts. CD4 count and HIV RNA viral load (VL) were collected for HIV+ pts. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 and B7-H3 (Abcam), and percent of tumor-infiltrating lymphocytes (TIL) expressing PD-1 and PD-L1 (Abcam). Positive expression was defined as > 5%. Statistical analysis was performed using the non-parametric Mann-Whitney test and the chi-square test. Proportions are specified as percentage with 95% confidence limits in parentheses. Results: Lung CA HIV+ case pts were predominantly male (62%), black race (100%), adenocarcinoma histology (77%), stage 4 disease (62%), and had a median age of 48 years. Of case pts with available data, mean CD4 count was 307 (range 37-617) and mean HIV VL was 29,400 (range 0-100,000). PD-L1 expression on tumor cells was positive in 23% (8%, 50%) of cases and 46% (23%, 71%) of controls. B7-H3 expression on tumor cells was positive in 92% (67%, 99%) of cases and 69% (42%, 87%) of controls. PD-1 expression on TIL was positive in 69% (42%, 87%) of cases and 54% (29%, 77%) of controls. PD-L1 expression on TIL was positive in 31% (13%, 58%) of cases and 69% (42%, 87%) of controls (p = 0.05). B7-H3 percent expression on tumor cells was significantly higher in cases vs controls (median 90% vs 20%, p = 0.005), but there were no significant differences in percent expression of PD-L1 on tumor cells, PD-1 on TIL or PD-L1 on TIL. Conclusions: HIV+ lung CA pts had significantly higher B7-H3 tumor percent expression compared to HIV-uninfected controls, with similar rates of PD-L1 tumor percent expression, PD-1 TIL percent expression and PD-L1 TIL percent expression. These results support inclusion of HIV+ lung CA pts in future immunotherapy trials.