Abstract
B7 homolog 3 (B7-H3) is a recently found superfamily B7 molecule and therefore has significant involvement in immunological regulation. However, the relationships of B7-H3 expression with the tumor microenvironment (TME), response to immunotherapy, and prognosis in head and neck squamous cell carcinoma (HNSCC) are still unknown. In the present analysis, we determined B7-H3 as a novel biomarker that predicts the prognosis and response to immunotherapy in HNSCC. B7-H3 expression is enhanced in HNSCC compared to normal sample and is stably expressed in HNSCC cell line. Besides, high B7-H3 expression is correlated with a dismal prognosis and resistance to immunotherapy and contributes to an immunosuppressive microenvironment. Moreover, single-cell RNA sequencing (scRNA-seq) analysis shows that B7-H3 is mainly expressed in the stromal as well as malignant cells. In conclusion, the study provides insight in understanding the prognostic value of B7-H3 in HNSCC and highlights its involvement in promoting the immunosuppressive microenvironment, which presents an attractive strategy for antibody-based immunotherapy.
Highlights
head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy globally, with a highly aggressive and heterogeneous phenotype [1, 2]
To further unveil the underlying mechanism of B7 homolog 3 (B7-H3) differential expression, we examined the relationship between RNA expression and B7-H3 methylation level
We identified B7-H3 as a novel biomarker that predicted the prognosis and response to immunotherapy in HNSCC
Summary
HNSCC is the sixth most common malignancy globally, with a highly aggressive and heterogeneous phenotype [1, 2]. Immunotherapy has been successful in many solid tumors including HNSCC, notably immune checkpoint inhibitors which hold great promise for treating malignancies. B7-H3 Is an Immunotherapy Target only a few patients experience clinical benefits from immunotherapy [4,5,6,7]. It is critical to identify a novel target for immunotherapy and exploit predictive biomarkers that stratify patients who may benefit from immunotherapy in head and neck cancer. B7 superfamily molecules play essential roles in regulating anti-tumor immunity. B7-H1 termed as programmed death-ligand 1 (PD-L1) is a critical immune checkpoint molecule that has a predominantly inhibitory role in adaptive immunity and suppresses proliferation as well as activation of T cells [8,9,10]. Previous reports have shown that B7-H3 is overexpressed in several tumor tissue types, which limit CD4+ and CD8+ T cells proliferation and may be exploited as a potential immunotherapy target [12,13,14,15]
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