دورية أكاديمية
CXCL5-mediated accumulation of mature neutrophils in lung cancer tissues impairs the differentiation program of anticancer CD8 T cells and limits the efficacy of checkpoint inhibitors
| العنوان: | CXCL5-mediated accumulation of mature neutrophils in lung cancer tissues impairs the differentiation program of anticancer CD8 T cells and limits the efficacy of checkpoint inhibitors |
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| المؤلفون: | Francesca Simoncello, Giulia Maria Piperno, Nicoletta Caronni, Roberto Amadio, Ambra Cappelletto, Giulia Canarutto, Silvano Piazza, Silvio Bicciato, Federica Benvenuti |
| المصدر: | OncoImmunology, Vol 11, Iss 1 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | Tumor-infiltrating neutrophils, lung cancer, effector CD8 T cells, immunotherapy, CXCL5, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Lung tumor-infiltrating neutrophils are known to support growth and dissemination of cancer cells and to suppress T cell responses. However, the precise impact of tissue neutrophils on programming and differentiation of anticancer CD8 T cells in vivo remains poorly understood. Here, we identified cancer cell-autonomous secretion of CXCL5 as sufficient to drive infiltration of mature, protumorigenic neutrophils in a mouse model of non-small cell lung cancer (NSCLC). Consistently, CXCL5 transcripts correlate with neutrophil density and poor prognosis in a large human lung adenocarcinoma compendium. CXCL5 genetic deletion, unlike antibody-mediated depletion, completely and selectively prevented neutrophils accumulation in lung tissues. Depletion of tumor-infiltrating neutrophils promoted expansion of tumor-specific CD8 T cells, differentiation into effector cells and acquisition of cytolytic functions. Transfer of effector CD8 T cells into neutrophil-rich tumors, inhibited IFN-ϒ production, indicating active suppression of effector functions. Importantly, blocking neutrophils infiltration in the lung, overcame resistance to checkpoint blockade. Hence, this study demonstrates that neutrophils curb acquisition of cytolytic functions in lung tumor tissues and suggests targeting of CXCL5 as a strategy to restore anti-tumoral T cell functions. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2022.2059876 |
| URL الوصول: | https://doaj.org/article/3cc3832c6ebb4043a0769d160d0b66d7 |
| رقم الأكسشن: | edsdoj.3cc3832c6ebb4043a0769d160d0b66d7 |
| قاعدة البيانات: | Directory of Open Access Journals |
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Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2022.2059876 |