Multi-Omics Data Analyses Identify B7-H3 as a Novel Prognostic Biomarker and Predict Response to Immune Checkpoint Blockade in Head and Neck Squamous Cell Carcinoma

Front Immunol. 2021 Oct 5:12:757047. doi: 10.3389/fimmu.2021.757047. eCollection 2021.

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.

Keywords: B7-H3; HNSCC; immune checkpoint; immunotherapy; prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • B7 Antigens / biosynthesis*
  • B7 Antigens / genetics
  • Base Sequence
  • Biomarkers
  • Cell Line, Transformed
  • Genomics / methods*
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use*
  • Immunotherapy*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / blood*
  • Membrane Proteins / genetics
  • Nasopharynx / cytology
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / blood*
  • Neoplasm Proteins / genetics
  • Prognosis
  • Proteomics / methods*
  • RNA, Neoplasm / biosynthesis
  • Single-Cell Analysis
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / metabolism*
  • Squamous Cell Carcinoma of Head and Neck / therapy
  • Stromal Cells / metabolism
  • Treatment Outcome
  • Tumor Microenvironment

Substances

  • Antibodies, Monoclonal, Humanized
  • B7 Antigens
  • Biomarkers
  • CD276 protein, human
  • Immune Checkpoint Inhibitors
  • Membrane Proteins
  • Neoplasm Proteins
  • RNA, Neoplasm
  • atezolizumab