Interplay between B7–H3 and HLA class I in the clinical course of pancreatic ductal adenocarcinoma

Human leukocyte antigen (HLA) class I defects are associated with cancer progression. However, their prognostic significance is controversial and may be modulated by immune checkpoints. Here, we investigated whether the checkpoint B7–H3 modulates the relationship between HLA class I and pancreatic ductal adenocarcinoma (PDAC) prognosis. PDAC tumors were analyzed for the expression of B7–H3, HLA class I, HLA class II molecules, and for the presence of tumor-infiltrating immune cells. We observed defective HLA class I and HLA class II expressions in 75% and 59% of PDAC samples, respectively. HLA class I and B7–H3 expression were positively related at mRNA and protein level, potentially because of shared regulation by RELA, a sub-unit of NF-kB. High B7–H3 expression and low CD8+ T cell density were indicators of poor survival, while HLA class I was not. Defective HLA class I expression was associated with unfavorable survival only in patients with low B7–H3 expression. Favorable survival was observed only when HLA class I expression was high and B7–H3 expression low. Our results provide the rationale for targeting B7–H3 in patients with PDAC tumors displaying high HLA class I levels.