دورية أكاديمية
A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system
| العنوان: | A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system |
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| المؤلفون: | Aude Burlion, Rodrigo N. Ramos, Pukar KC, Kélhia Sendeyo, Aurélien Corneau, Christine Ménétrier-Caux, Eliane Piaggio, Daniel Olive, Christophe Caux, Gilles Marodon |
| المصدر: | OncoImmunology, Vol 8, Iss 7 (2019) |
| بيانات النشر: | Taylor & Francis Group, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | icos, humanized mice, regulatory t cells, chemotherapy, immunotherapy, cyclophosphamide, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Mice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapies. Here, we used mass cytometry and multi-parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in immunocompromised NOD.SCID.γc-null mice reconstituted with a human immune system and compared it to samples of breast cancer patients. We observed highly activated human CD4+ and CD8+ T cells in the tumor, as well as minor subsets of innate immune cells in both settings. We also report that ICOS+ CD4+ regulatory T cells (Treg) were enriched in the tumor relative to the periphery in humanized mice and patients, providing a target to affect Treg and tumor growth. Indeed, administration of a neutralizing mAb to human ICOS reduced Treg proportions and numbers and improved CD4 + T cell proliferation in humanized mice. Moreover, a combination of the anti-ICOS mAb with cyclophosphamide reduced tumor growth, and that was associated with an improved CD8 to Treg ratio. Depletion of human CD8+ T cells or of murine myeloid cells marginally affected the effect of the combination therapy. Altogether, our results indicate that a combination of anti-ICOS mAb and chemotherapy controls tumor growth in humanized mice, opening new perspectives for the treatment of breast cancer. One sentence summary: Targeting ICOS in combination with chemotherapy is a promising strategy to improve tumor immunity in humans. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162-402X 2162402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2019.1596005 |
| URL الوصول: | https://doaj.org/article/a4b2d12d23bf4555bb996cf40e2ecd59 |
| رقم الأكسشن: | edsdoj.4b2d12d23bf4555bb996cf40e2ecd59 |
| قاعدة البيانات: | Directory of Open Access Journals |
PDF full text from Publisher | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2019.1596005 |