KEY TAKEAWAYS
- The study aimed to investigate the impact of CD47 expression changes during platinum therapy on immune features and prognosis in OC.
- Researchers noted that CD47 stratification improves immunotherapy targeting, and TAX2 may be an alternative for PARP-resistant cases.
Ovarian cancer (OC) remains 1 of the most challenging and deadly malignancies facing women today. While PARP inhibitors (PARPis) have transformed the treatment landscape for women with advanced OC, many patients will relapse, and the PARPi-resistant setting is an area of unmet medical need. Traditional immunotherapies targeting PD-1/PD-L1 have failed to show any benefit in OC. The CD47/TSP-1 axis may be relevant in OC.
Aurélie Moniot and the team aimed to describe changes in CD47 expression with platinum therapy and their relationship with immune features and prognosis.
They performed an inclusive analysis of tumor and blood samples collected from patients with OC in the CHIVA trial, assessing CD47 and TSP-1 levels before and after neoadjuvant chemotherapy (NACT). Multiplex analysis was employed to investigate immune markers.
Considering the therapeutic relevance of targeting the CD47/TSP-1 axis, the CD47-derived TAX2 peptide was used to selectively antagonize this axis in a preclinical model of aggressive ovarian carcinoma.
Significant reductions in CD47 expression were observed post-NACT, and patients with the highest baseline CD47 expression exhibited the greatest CD4+ and CD8+ T-cell influx and a better prognosis. Additionally, TSP-1 plasma levels significantly decreased under NACT, with high TSP-1 correlating to a worse prognosis.
TAX2 demonstrated a selective and favorable biodistribution profile in mice, localizing at tumor sites. In a peritoneal carcinomatosis model displaying PARPi resistance, post-olaparib administration of TAX2 significantly reduced tumor burden and prolonged survival. Notably, sequential use of TAX2 also enhanced survival even when olaparib efficacy was preserved.
The study concluded that CD47-based stratification could identify patients most likely to benefit from postoperative immunotherapy and suggested that TAX2 might serve as a potential alternative therapy for patients relapsing on PARP inhibitors.
This study was funded by the Institut National du Cancer (INCa, PLBIO 2020, PI: SD) and Apmonia Therapeutics.
Source: https://pubmed.ncbi.nlm.nih.gov/39138571/
Moniot A, Schneider C, Chardin L, et al. (2024). “The CD47/TSP-1 axis: a promising avenue for ovarian cancer treatment and biomarker research.” Mol Cancer. 2024;23(1):166. Published 2024 Aug 14. doi:10.1186/s12943-024-02073-0
