Data from The First-week Proliferative Response of Peripheral Blood PD-1+CD8+ T Cells Predicts the Response to Anti-PD-1 Therapy in Solid Tumors
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AbstractPurpose: To investigate blood-based dynamic biomarkers that predict responses to anti–programmed cell death protein 1 (PD-1) therapy in solid tumors. Experimental Design: Preplanned biomarker analysis was performed as part of a phase II clinical trial (NCT02607631) in patients with metastatic or refractory thymic epithelial tumors (TETs; n = 31) who received pembrolizumab. The biomarker was further tested in an independent cohort of prospectively recruited patients with metastatic non–small cell lung cancer (NSCLC) who received pembrolizumab or nivolumab (NSCLC cohort 1; n = 33) and validated in an independent cohort of patients with NSCLC (NSCLC cohort 2; n = 46). Peripheral blood samples were obtained immediately before treatment (D0) and 7 days after the first dose (D7) and analyzed using multi-color flow cytometry. Results: A higher fold-change in the percentage of Ki-67+ cells among PD-1+CD8+ T cells 7 days after the first dose (Ki-67D7/D0) significantly predicted durable clinical benefit (DCB; P < 0.001) and prolonged progression-free survival (PFS; P = 0.027) in patients with TETs. Ki-67D7/D0 ≥ 2.8 was also associated with better DCB, PFS, and overall survival (OS) in NSCLC cohort 1 (all P < 0.05). Ki-67D7/D0 was subsequently validated in NSCLC cohort 2, and Ki-67D7/D0 ≥ 2.8 significantly predicted better DCB (P = 0.001), PFS (P = 0.002), and OS (P = 0.037). Ki-67D7/D0 had a low correlation with tumor PD-L1 expression and combining both factors did not improve the predictive power of Ki-67D7/D0. Conclusions: The proliferative response of peripheral blood PD-1+CD8+ T cells, measured as the fold-change in the percentage of Ki-67+ cells 7 days after treatment (Ki-67D7/D0), may be a useful surrogate biomarker for predicting the response and prognosis to anti-PD-1 therapy in solid tumors.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé, mais le titre doit être comparé manuellement.
- Titre Crossref
- Data from The First-week Proliferative Response of Peripheral Blood PD-1<sup>+</sup>CD8<sup>+</sup> T Cells Predicts the Response to Anti-PD-1 Therapy in Solid Tumors
- Date Crossref
- 31/03/2023
- Éditeur
- American Association for Cancer Research (AACR)
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.