دورية أكاديمية
Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response
| العنوان: | Tbc1d10c is a selective, constitutive suppressor of the CD8 T-cell anti-tumor response |
|---|---|
| المؤلفون: | Adrienne O. Cohen, Seung-Hyun Woo, Junya Zhang, Jiyoon Cho, Marlon E. Ruiz, Jianli Gong, Rong Du, Olga Yarygina, Danya Z. Jafri, Michael A. Bachelor, Michael O. Finlayson, Rajesh K. Soni, Matthew S. Hayden, David M. Owens |
| 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: | Immuno-oncology, squamous cell carcinoma, melanoma, carabin, NF-κB, Map3k3, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | Cancer immunotherapy approaches target signaling pathways that are highly synonymous between CD4 and CD8 T-cell subsets and, therefore, often stimulate nonspecific lymphocyte activation, resulting in cytotoxicity to otherwise healthy tissue. The goal of our study was to identify intrinsic modulators of basic T lymphocyte activation pathways that could discriminately bolster CD8 anti-tumor effector responses. Using a Tbc1d10c null mouse, we observed marked resistance to a range of tumor types conferred by Tbc1d10c deficiency. Moreover, tumor-bearing Tbc1d10c null mice receiving PD-1 or CTLA-4 monotherapy exhibited a 33% or 90% cure rate, respectively. While Tbc1d10c was not expressed in solid tumor cells, Tbc1d10c disruption selectively augmented CD8 T-cell activation and cytotoxic effector responses and adoptive transfer of CD8 T cells alone was sufficient to recapitulate Tbc1d10c null tumor resistance. Mechanistically, Tbc1d10c suppressed CD8 T-cell activation and anti-tumor function by intersecting canonical NF-κB pathway activation via regulation of Map3k3-mediated IKKβ phosphorylation. Strikingly, none of these cellular or molecular perturbations in the NF-κB pathway were featured in Tbc1d10c null CD4 T cells. Our findings identify a Tbc1d10c-Map3k3-NF-κB signaling axis as a viable therapeutic target to promote CD8 T-cell anti-tumor immunity while circumventing CD4 T cell-associated cytotoxicity and NF-κB activation in tumor cells. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162402X 2162-402X |
| Relation: | https://doaj.org/toc/2162-402X |
| DOI: | 10.1080/2162402X.2022.2141011 |
| URL الوصول: | https://doaj.org/article/8934c8d8d72d4713bd473109738422f3 |
| رقم الأكسشن: | edsdoj.8934c8d8d72d4713bd473109738422f3 |
| قاعدة البيانات: | Directory of Open Access Journals |
PDF full text from Publisher 
Full Text Finder | تدمد: | 2162402X |
|---|---|
| DOI: | 10.1080/2162402X.2022.2141011 |