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The prognostic impact of B7-H3 and B7-H4 in head and neck squamous cell carcinoma
Mara Borgmann1,2, Agnes Oetting1,3, Felix Meyer3
1Department of Otorhinolaryngology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Purpose:
Immune checkpoint inhibition is a therapeutic option in many cancer entities. In head and neck squamous cell carcinoma (HNSCC) targeting of the PD-1/PD-L1 (B7-H1) axis is approved in recurrent/metastatic disease and is being explored in the curative setting. Here, we evaluated two related members of the B7 family, B7-H3 & B7-H4, for their prognostic impact under standard treatment.
Methods:
A tissue microarray (TMA) of a single center HNSCC cohort was stained for B7-H3 and B7-H4. Staining intensity and the number of tumor cells stained were assessed, and the expression was scored according to an established algorithm. Staining scores were correlated with clinicopathological parameters and associated with patient survival. mRNA levels of both proteins were associated with patient outcome using the TCGA dataset.
Results:
mRNA levels of B7-H3 and B7-H4 were not significantly associated with patient survival. TMA analysis revealed interpretable protein staining in 408 samples. Strong staining was the most frequent category for B7-H3 and no staining for B7-H4. In patients with p16-negative oropharyngeal SCC (OPSCC) and in a pooled cohort consisting of p16-negative OPSCC, laryngeal, hypopharyngeal and oral cavity SCC, strong B7-H3 expression was associated with better overall survival. For the latter cohort, this was in part due to reduced lymph node involvement. B7-H3 expression in p16-positive OPSCC and B7-H4 expression were not associated with outcome.
Conclusion:
Despite a possible role in tumor immune escape, B7-H3 was associated with favorable prognosis in HPV-negative HNSCC in our cohort. The underlying mechanisms and a potential impact for B7-H3 targeting remain to be elucidated.
Insights
B7-H3 expression indicates a favorable prognosis in HPV-negative head and neck squamous cell carcinoma (HNSCC). Further research is needed to understand the mechanisms and therapeutic potential of B7-H3 targeting in HNSCC.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Immune checkpoint inhibitors targeting PD-1/PD-L1 are established treatments for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
- The prognostic significance of other B7 family members, specifically B7-H3 and B7-H4, in HNSCC requires further investigation.
Purpose of the Study:
- To evaluate the prognostic impact of B7-H3 and B7-H4 expression in a cohort of patients with HNSCC undergoing standard treatment.
- To correlate protein expression levels with clinicopathological parameters and patient survival outcomes.
Main Methods:
- A tissue microarray (TMA) from a single-center HNSCC cohort was utilized for B7-H3 and B7-H4 protein expression analysis.
- Immunohistochemical staining was scored, and results were correlated with clinicopathological data and patient survival.
- Messenger RNA (mRNA) levels of B7-H3 and B7-H4 were analyzed using The Cancer Genome Atlas (TCGA) dataset to assess their association with patient outcomes.
Main Results:
- While mRNA levels of B7-H3 and B7-H4 did not significantly correlate with survival, TMA analysis of protein expression revealed key findings.
- Strong B7-H3 expression was associated with improved overall survival in patients with p16-negative oropharyngeal SCC (OPSCC) and a pooled cohort of HPV-negative HNSCC subtypes (laryngeal, hypopharyngeal, oral cavity).
- This improved survival in the pooled cohort was partly attributed to reduced lymph node involvement. B7-H3 expression in p16-positive OPSCC and B7-H4 expression showed no significant association with patient outcomes.
Conclusions:
- B7-H3 expression is linked to a favorable prognosis in HPV-negative HNSCC, despite its potential role in immune evasion.
- The specific mechanisms underlying this association and the potential for therapeutic targeting of B7-H3 in HNSCC warrant further investigation.
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