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 no:Journal of Extracellular Vesicles vol. 14, no. 4 (Apr 1, 2025)
Autor principal: Sun, Linzi
Outros 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
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022 |a 2001-3078 
024 7 |a 10.1002/jev2.70054  |2 doi 
035 |a 3217503482 
045 0 |b d20250401 
084 |a 211029  |2 nlm 
100 1 |a Sun, Linzi  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
245 1 |a Dynamic Change of PD‐L2 on Circulating Plasma Extracellular Vesicles as a Predictor of Treatment Response in Melanoma Patients Receiving Anti‐PD‐1 Therapy 
260 |b John Wiley & Sons, Inc.  |c Apr 1, 2025 
513 |a Journal Article 
520 3 |a 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. 
610 4 |a Peking University 
651 4 |a Beijing China 
651 4 |a United States--US 
651 4 |a China 
653 |a Plasma 
653 |a Metastasis 
653 |a Immunotherapy 
653 |a Antibodies 
653 |a Granzyme B 
653 |a Immune checkpoint inhibitors 
653 |a Lymphocytes T 
653 |a Cell lines 
653 |a Extracellular vesicles 
653 |a Peripheral blood mononuclear cells 
653 |a Penicillin 
653 |a Angiogenesis 
653 |a Cell activation 
653 |a Proteins 
653 |a Patients 
653 |a Protein arrays 
653 |a Biomarkers 
653 |a Melanoma 
653 |a Response rates 
653 |a Leukocytes (mononuclear) 
653 |a CD8 antigen 
700 1 |a Wei, Xiaoting  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Zhao, Qian  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Mao, Lili  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Bai, Xue  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Li, Caili  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Gu, Junjie  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Kong, Yan  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Cui, Chuanliang  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Chi, Zhihong  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Sheng, Xinan  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Lian, Bin  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Wang, Xuan  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Li, Siming  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Yan, Xieqiao  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Tang, Bixia  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Zhou, Li  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Li, Juan  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Guo, Jun  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Si, Lu  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
700 1 |a Dai, Jie  |u Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China 
773 0 |t Journal of Extracellular Vesicles  |g vol. 14, no. 4 (Apr 1, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3217503482/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3217503482/fulltext/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
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