Association of BTN2A1+ microvesicles with overall survival and the role of γδ T cells as a potential therapeutic target in patients with hormone-sensitive metastatic prostate cancer.

• DOI: 10.1200/jco.2024.42.4_suppl.194
• Publication Date: 2024-01-29T21:06:41Z
• Authors: Emilien Billon; Caroline Imbert; Laurent Gorvel; Manon Richaud; Rania Ghossoub; Virginie Girault; Thierry Fest; Gwenaelle Gravis; Daniel Olive
• Keywords: Circulating tumor cell

194 Background: Despite the recent progress in cancer management, metastatic prostate remains incurable. In context of immunotherapy failure, we need to identify new immune biomarkers, improve patient therapy, and explore their potential as therapeutic target. To this end, screened prognostic value soluble checkpoints plasma patients at diagnosis, depicted role anti-tumor activities. Methods: Patients with hormone naive were prospectively included NK-Prostate study (NCT02963155). Blood collection was performed before treatment followed for 5 years. We determined by ELISA assay levels form PD-L1, Pan-BTN3A, BTN3A1, BTN2A1 BTLA. Large extracellular vesicles (MVs) pelleted 10 000g sequential ultracentrifugation. Results: 66 a median follow-up 42.6 months. Only associated overall survival > 50 enriched sBTN2A1 (soluble BTN2A1) presented poorer (HR death 2.91 95%CI 1.33 – 6.33, p=0.0072) progression-free than low-level progression 2.73 1.48 5.05, p=0.0012). Prostate cell line produced sBTN2A1, 40% vesicles. High level BTN2A1+ microvesicles identified spectral cytometry patient’ but not healthy volunteer plasma, deep phenotyping revealed that B cell-derived MVs shorter 4.22 1.68 10.57, p=0.0021). evaluate impact on γδ T cells, generated KO MVs, overexpressed mutant (that do interact TCR). demonstrated could specifically cell; impaired proliferation cytotoxicity against lines (LNCaP, DU145 PC3). Conclusions: Our shows negative derived naïve cancer. Plasma is an easy-to-perform test, accessible all patients. results highlight immunity cancer, making them interesting target pathology. Clinical trial information: NCT02963155 .