دورية أكاديمية
Intratumoral dendritic cell-CD4
| العنوان: | Intratumoral dendritic cell-CD4 |
|---|---|
| المؤلفون: | Magen, Assaf, Hamon, Pauline, Fiaschi, Nathalie, Soong, Brian Y, Park, Matthew D, Mattiuz, Raphaël, Humblin, Etienne, Troncoso, Leanna, D'souza, Darwin, Dawson, Travis, Kim, Joel, Hamel, Steven, Buckup, Mark, Chang, Christie, Tabachnikova, Alexandra, Schwartz, Hara, Malissen, Nausicaa, Lavin, Yonit, Soares-Schanoski, Alessandra, Giotti, Bruno, Hegde, Samarth, Ioannou, Giorgio, Gonzalez-Kozlova, Edgar, Hennequin, Clotilde, Le Berichel, Jessica, Zhao, Zhen, Ward, Stephen C, Fiel, Isabel, Kou, Baijun, Dobosz, Michael, Li, Lianjie, Adler, Christina, Ni, Min, Wei, Yi, Wang, Wei, Atwal, Gurinder S, Kundu, Kunal, Cygan, Kamil J, Tsankov, Alexander M, Rahman, Adeeb, Price, Colles, Fernandez, Nicolas, He, Jiang, Gupta, Namita T, Kim-Schulze, Seunghee, Gnjatic, Sacha, Kenigsberg, Ephraim, Deering, Raquel P, Schwartz, Myron, Marron, Thomas U, Thurston, Gavin, Kamphorst, Alice O, Merad, Miriam |
| المصدر: | Nat Med ; ISSN:1546-170X ; Volume:29 ; Issue:6 |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2023 |
| المجموعة: | PubMed Central (PMC) |
| الوصف: | Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). We leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC), as well as additional samples collected from patients treated off-label, to explore correlates of response to ICB within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13+CH25H+IL-21+PD-1+CD4+ T helper cells ("CXCL13+ TH") and Granzyme K+ PD-1+ effector-like CD8+ T cells, whereas terminally exhausted CD39hiTOXhiPD-1hiCD8+ T cells dominated in nonresponders. CD4+ and CD8+ T cell clones that expanded post-treatment were found in pretreatment biopsies. Notably, PD-1+TCF-1+ (Progenitor-exhausted) CD8+ T cells shared clones mainly with effector-like cells in responders or terminally exhausted cells in nonresponders, suggesting that local CD8+ T cell differentiation occurs upon ICB. We found that these Progenitor CD8+ T cells interact with CXCL13+ TH within cellular triads around dendritic cells enriched in maturation and regulatory molecules, or "mregDC". These results suggest that discrete intratumoral niches that include mregDC and CXCL13+ TH control the differentiation of tumor-specific Progenitor exhasuted CD8+ T cells following ICB. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1038/s41591-023-02345-0Test; https://pubmed.ncbi.nlm.nih.gov/37322116Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027932Test/ |
| DOI: | 10.1038/s41591-023-02345-0 |
| الإتاحة: | https://doi.org/10.1038/s41591-023-02345-0Test https://pubmed.ncbi.nlm.nih.gov/37322116Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027932Test/ |
| حقوق: | © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc. |
| رقم الانضمام: | edsbas.ADDE436F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41591-023-02345-0 |
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