Abstract
BackgroundIt has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. However, the application of the B7H4-PDL1 classifier in cancers has not been well testified.MethodsA pan-cancer analysis was conducted to evaluate the immunological role of B7H4 using the RNA-sequencing data downloaded from the Cancer Genome Atlas (TCGA). Immunohistochemistry (IHC) and multiplexed quantitative immunofluorescence (QIF) were performed to validate the primary results revealed by bioinformatics analysis.ResultsThe pan-cancer analysis revealed that B7H4 was negatively correlated with PDL1 expression and immune cell infiltration in CeCa. In addition, patients with high B7H4 exhibited the shortest overall survival (OS) and relapse-free survival (RFS) while those with high PDL1 exhibited a better prognosis. Multiplexed QIF showed that B7H4 was mutually exclusive with PDL1 expression and the B7H4-high group exhibited the lowest CD8 + T cell infiltration. Besides, B7H4-high predicted highly proliferative subtypes, which expressed the highest Ki67 antigen. Moreover, B7H4-high also indicated a lower response to multiple therapies.ConclusionsTotally, the B7H4-PDL1 classifier identifies the immunogenicity and predicts proliferative subtypes and limited therapeutic options in CeCa, which may be a convenient and feasible biomarker in clinical practice.
Highlights
It has been revealed that B7H4 is negatively correlated with programmed death-ligand 1 (PDL1) and identifies immuno-cold tumors in glioma
Representative immune checkpoint inhibitors are monoclonal antibodies that interfere with the interaction between programmed cell death 1 (PD1) and programmed death-ligand 1 (PDL1) inhibitory proteins expressed on the surface of T cells and tumor cells, respectively [2, 3]
The prognostic value of the B7H4‐PDL1 classifier in glioma According to the report of Chen et al, the positive rates of B7H4 and PDL1 were approximately 20% revealed by IHC analysis [13]
Summary
It has been revealed that B7H4 is negatively correlated with PDL1 and identifies immuno-cold tumors in glioma. The application of the B7H4-PDL1 classifier in cancers has not been well testified. With the development of treatment strategies for malignant cancers, immune checkpoint blockade (ICB) is emerging as inspiring immunotherapy transforming the standard of treatment [1]. Representative immune checkpoint inhibitors are monoclonal antibodies that interfere with the interaction between programmed cell death 1 (PD1) and programmed death-ligand 1 (PDL1) inhibitory proteins expressed on the surface of T cells and tumor cells, respectively [2, 3]. In addition to PDL1, B7H4 is highly expressed in tumor tissues, making them attractive candidate immunotherapeutic targets and biomarkers [7, 8]. Co-expression of PDL1 and B7H4 is rare in
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