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Dynamic Change of PD‐L2 on Circulating Plasma Extracellular Vesicles as a Predictor of Treatment Response in Melanoma Patients Receiving Anti‐PD‐1 Therapy

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Publicado en:Journal of Extracellular Vesicles vol. 14, no. 4 (Apr 1, 2025)
Autor principal: Sun, Linzi
Otros Autores: Wei, Xiaoting, Zhao, Qian, Mao, Lili, Bai, Xue, Li, Caili, Gu, Junjie, Kong, Yan, Cui, Chuanliang, Chi, Zhihong, Sheng, Xinan, Lian, Bin, Wang, Xuan, Li, Siming, Yan, Xieqiao, Tang, Bixia, Zhou, Li, Li, Juan, Guo, Jun, Si, Lu, Dai, Jie
Publicado:
John Wiley & Sons, Inc.
Materias:
Peking University
Beijing China
United States > US
China
Plasma
Metastasis
Immunotherapy
Antibodies
Granzyme B
Immune checkpoint inhibitors
Lymphocytes T
Cell lines
Extracellular vesicles
Peripheral blood mononuclear cells
Penicillin
Angiogenesis
Cell activation
Proteins
Patients
Protein arrays
Biomarkers
Melanoma
Response rates
Leukocytes (mononuclear)
CD8 antigen
Acceso en línea:Citation/Abstract
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Resumen:ABSTRACT Immune checkpoint inhibitors (ICIs) have provided new hope for melanoma patients, however, not all patients benefit. Furthermore, ICI‐related therapies cause significant immune‐related adverse events that adversely affect patient outcomes. Therefore, there is a pressing need for reliable biomarkers to identify patients most likely to benefit from these treatments. In this study, we employed an extracellular vesicles (EVs) protein expression array to explore the longitudinal membrane protein profiles of plasma‐derived EVs from 32 melanoma patients receiving anti‐PD‐1 and anti‐angiogenesis therapy at baseline and early treatment. We found that the dynamic changes in PD‐L2 on the EV membrane were associated with treatment response and patient survival. The dynamic change of EV PD‐L2 as an indication of treatment efficacy was validated in an independent cohort of melanoma patients treated with anti‐PD‐1 monotherapy. Plasma‐derived PD‐L2+ EVs from patients with mucosal melanoma significantly reduced the frequency of granzyme B+ CD8 T cells within the peripheral blood mononuclear cells (PBMCs) of healthy individuals. The inhibitory effect of PD‐L2+ EVs on CD8 T cells was further validated using human melanoma cell lines and the B16‐F10 mouse model. Although intratumoural injection of PD‐L2+ EVs could promote melanoma growth in vivo, tumours with PD‐L2+ EVs showed a higher response to anti‐PD‐1 than those without PD‐L2+ EVs. Collectively, our study demonstrates that PD‐L2+ EVs inhibit CD8 T cell activation and promote melanoma growth, and changes in PD‐L2 on circulating EVs during early treatment could serve as a biomarker for ICI‐based therapy.
ISSN:2001-3078
DOI:10.1002/jev2.70054
Fuente:Biological Science Database