The prognostic impact of B7-H3 and B7-H4 in head and neck squamous cell carcinoma

Abstract

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.

Prognostic Value of B7H4 Expression in Patients with Solid Cancers: A Systematic Review and Meta-Analysis

“…The studies were published between 2007 and 2023. They consisted of the following cancer types: OS-osteosarcoma [27], Pca-prostate cancer [28,29], CvC-cervical cancer [30,31], CCA-cholangiocarcinoma [13,32], PDAC-pancreatic ductal adenocarcinoma [33][34][35][36], UCC-urothelial cell carcinoma [36], HNSCC-head and neck squamous cell carcinoma [37,38], OC-ovarian cancer [39], ESCC-esophageal squamous cell carcinoma [28,40], BC-breast cancer [41,42], GC-gastric cancer [43,44], ECC-endometrial cancer [45], NSCLC-non-squamous cell lung carcinoma [46,47], RCC-renal cell carcinoma [48], and CRC-colorectal cancer [39,[49][50][51][52]. The sample sizes ranged from 37 to 996, with a total of 6357 patients.…”

The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study

“…For instance, it has been suggested that the overexpression of B7-H3 was associated with lymph node and distant metastasis in lung adenocarcinoma [ 20 ]. High B7-H3 expression has been reported as a favorable prognostic factor in patients with squamous cell carcinoma of the head and neck [ 21 ]. Furthermore, there are two isoforms of B7-H3 [ 22 ], but it has not been confirmed which isoform the B7-H3 used in this study recognizes.…”

“…These findings are consistent with the results of this study, wherein we observed an increase in the density of CD8 + TILs in tumors with low B7-H3 expression. In NSCLC, tumor cells expressing B7-H3 may promote immune tolerance by avoiding CD8 + T-cell damage [ 21 , 26 ]. Therefore, low stromal B7-H3 levels in LSCC may activate the local immune system to promote CD8 + T-cell invasion.…”

The Concordant Disruption of B7/CD28 Immune Regulators Predicts the Prognosis of Oral Carcinomas

“…Lower ICOS expression also had a worse prognosis in node-positive OSCC. The roles of CD276 as an immune-inhibitory factor in predicting HNSCC survival were much more clearly defined in this study [ 16 , 18 , 19 , 20 ]. Furthermore, a lower CD276/ICOS or higher ICOS was a marker predicting better survival of all patients and patients with nodal metastasis.…”

“…Although many interactive partners of CD276 have been found [ 15 ], the receptor of CD276 has not been identified thus far. Recent studies have shown that CD276 may exert inhibitory activities against immunity in HNSCC [ 5 , 16 , 17 , 18 , 19 , 20 ]. CD276 enables HNSCC stem cells to escape immune surveillance [ 18 ].…”