Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 1336 |
| Journal | BMC cancer |
| Volume | 24 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2024 |
Funding
Meghan M. Lynch reports no conflicts of interest in this work. Rusul Almarayaty reports no conflicts of interest in this work. Farres Obeidin reports no conflicts of interest in this work. Borislav A. Alexiev reports no conflicts of interest in this work. Eleanor Chen reports no conflicts of interest in this work. Pedro Vivieros receives consulting, advisory from, Deciphera and speakers fee from Springworks. Brett A. Schroeder reports no conflicts of interest in this work. Kelly Hudkins reports no conflicts of interest in this work. Timothy M. Fan reports the following conflicts of interest: consulting or advisory role with Volition, research funding from Ankyra Therapeutics, and intellectual property through SHIELDT3. Mary W. Redman reports no conflicts of interest in this work. Kelsey K. Baker reports no conflicts of interest in this work. George Jour reports no conflicts of interest in this work. Lee D. Cranmer receives research funding (paid to institution) from AADI Biosciences, Avacta, Merck, Gradalis, Inhibrx, Monopar, Eli Lilly, Exelixis, Boehringer Ingelheim. He has received consulting, advisory and speaker fees from AADi Biosciences, Boehringer Ingelheim, Deciphera and Avacta. Dr. Cranmer\u2019s work is supported, in part, by the Curt and Elizabeth Anderson Endowed Professorship in Sarcoma Research at the University of Washington. Seth M. Pollack receives research funding from Obsidian Therapeutics. He receives consulting, advisory and speaker fees from Bayer, Deciphera, Springworks, Sensei Therapeutics, Aadi Therapeutics, and Epizyme. This study was funded by the National Cancer Institute, R01CA244872 and the Gilman Sarcoma Foundation.
Keywords
- B7-H3
- Immunotherapy
- Sarcoma
- Soft tissue sarcoma
- Therapeutic target
ASJC Scopus subject areas
- Oncology
- Genetics
- Cancer Research
