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Published on: January 3, 2013
B7-H3 is widely expressed in soft tissue sarcomas
Meghan M Lynch1, Rusul Al-Marayaty2, Farres Obeidin3
1Department of Internal Medicine, Northwestern University, Chicago, IL, USA.
Purpose:
Targeted therapy development in soft tissue sarcoma (STS) has been burdened by the heterogeneity of this group of rare tumors. B7 homolog 3 protein (B7-H3) is a molecule in the same family as programmed death-ligand 1 (PD-L1). It has limited expression in noncancerous tissues and is overexpressed in many cancers, making it an attractive target for cancer therapy, and clinical trials targeting B7-H3 are actively underway. While available data demonstrate high expression levels of B7-H3 in individual sarcoma subtypes, its expression patterns across STS subtypes are not well described. The purpose of this study was to characterize the expression patterns of B7-H3 in STS.
Patients And Methods:
This retrospective analysis evaluated STS tumor specimens from patients with a variety of different subtypes. Specimens were evaluated by immunohistochemistry (IHC) for expression and staining pattern of B7-H3 both in tumors and in associated vasculature.
Results:
Specimens from 153 sarcoma patients included 15 different STS subtypes. B7-H3 was broadly expressed in 97% of samples (95% CI 0.93-0.99) and 69.2% demonstrated high levels of B7-H3 expression (95% CI 0.61-0.76). No significant association between B7-H3 positivity or expression level and prior treatment(s), tumor size, tumor grade, or patient age. B7-H3 positivity in vessels was found in 94.7% (145/153) of samples. In tumors that had been previously assessed for PD-L1 and PD-1, there was no correlation between B7-H3 positivity or expression and the positivity or expression level of PD-L1 or PD-1.
Conclusion:
These data show high levels of B7-H3 positivity across soft tissue sarcoma subtypes, suggesting its feasibility as a therapeutic target for future sarcoma treatments. Future clinical trials are needed to evaluate whether targeting B7-H3 can provide clinical benefit to help patients with sarcoma.
Insights
B7-H3 protein is highly expressed in most soft tissue sarcoma (STS) subtypes, indicating its potential as a therapeutic target. Further clinical trials are necessary to confirm if targeting B7-H3 benefits sarcoma patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Soft tissue sarcoma (STS) is a rare and heterogeneous cancer, posing challenges for targeted therapy development.
- B7 homolog 3 protein (B7-H3) is an immune checkpoint molecule with limited expression in normal tissues but overexpressed in various cancers.
- B7-H3 is a promising target for cancer therapy, with ongoing clinical trials.
Purpose of the Study:
- To characterize the expression patterns of B7-H3 across different subtypes of soft tissue sarcoma.
- To evaluate B7-H3 as a potential therapeutic target in STS.
Main Methods:
- Retrospective analysis of 153 STS tumor specimens from 15 different subtypes.
- Immunohistochemistry (IHC) was used to assess B7-H3 expression and staining patterns in tumor cells and associated vasculature.
Main Results:
- B7-H3 was broadly expressed in 97% of STS samples, with 69.2% showing high expression levels.
- No significant association was found between B7-H3 expression and prior treatments, tumor size, grade, or patient age.
- B7-H3 was present in tumor vasculature in 94.7% of samples and showed no correlation with PD-L1 or PD-1 expression.
Conclusions:
- High B7-H3 positivity across diverse STS subtypes supports its feasibility as a therapeutic target.
- Further clinical trials are warranted to determine the efficacy of B7-H3 targeting in sarcoma treatment.
