دورية أكاديمية
Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade
العنوان: | Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade |
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المؤلفون: | Rivoltini, Licia, Camisaschi, Chiara, Fucà, Giovanni, Paolini, Biagio, Vergani, Barbara, Beretta, Valeria, Damian, Silvia, Duca, Matteo, Cresta, Sara, Magni, Michele, Leone, Biagio Eugenio, Castelli, Chiara, de Braud, Filippo, De Santis, Francesca, Di Nicola, Massimo |
المساهمون: | Rivoltini, L, Camisaschi, C, Fucà, G, Paolini, B, Vergani, B, Beretta, V, Damian, S, Duca, M, Cresta, S, Magni, M, Leone, B, Castelli, C, de Braud, F, De Santis, F, Di Nicola, M |
بيانات النشر: | Nature Publishing Group GB |
سنة النشر: | 2024 |
المجموعة: | Università degli Studi di Milano-Bicocca: BOA (Bicocca Open Archive) |
مصطلحات موضوعية: | triple-negative breast cancer, PD-1, LAG-3 |
الوصف: | In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1. In peripheral blood, baseline expression of LAG-3 and PD-1 was observed in circulating immune cells. Following treatment initiation, there was a rapid increase in proliferating granzyme-B+ NK and T cells, including CD4+ T cells, alongside a reduction in myeloid-derived suppressor cells. The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade. Trial registration: NCT02460224. Registered 02/06/2015. |
نوع الوثيقة: | article in journal/newspaper |
وصف الملف: | ELETTRONICO |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/38336861; info:eu-repo/semantics/altIdentifier/wos/WOS:001160750400058; volume:14; issue:1; journal:SCIENTIFIC REPORTS; https://hdl.handle.net/10281/460058Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85184786154 |
DOI: | 10.1038/s41598-024-54041-9 |
الإتاحة: | https://doi.org/10.1038/s41598-024-54041-9Test https://hdl.handle.net/10281/460058Test |
حقوق: | info:eu-repo/semantics/openAccess |
رقم الانضمام: | edsbas.2FA7593E |
قاعدة البيانات: | BASE |
DOI: | 10.1038/s41598-024-54041-9 |
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