CD80 and CD86: expression and prognostic value in newly diagnosed glioblastoma

Abstract

Purpose Strategies to modulate the tumor microenvironment (TME), including the vascular and immune components, have opened new therapeutic avenues with dramatic yet heterogeneous intertumor efficacy in multiple cancers, including brain malignancies. Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in glioblastoma (GBM) is still unclear. Methods In this study, we have investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. CD80 and CD86 at the protein level were also investigated in the discovery cohort. Results Both CD80 and CD86 are expressed heterogeneously in GBM at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both ONT and TCGA datasets. On the other hand, CD80 and CD86 mRNA high expression was significantly associated with shorter PFS (p<0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p<0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p<0.05). Conclusion Additional studies are warranted to validate our findings and to explore the expression of CD80 and CD86 in GBM patients treated with immunotherapy and, more specifically, with CTLA-4 inhibitors.