Enhancement of antitumor immunity by combination of anti-CTLA-4 antibody and radioimmunotherapy through the suppression of Tregs
| Autor: | Kwangmo Yang, Cheol‑Hun Son, Hong‑Rae Lee, You Soo Park, Jae-Ho Bae |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Cluster of differentiation medicine.medical_treatment ELISPOT hemic and immune systems chemical and pharmacologic phenomena Articles Immunotherapy Biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Immune system Oncology CTLA-4 030220 oncology & carcinogenesis Radioimmunotherapy Immunology medicine Cancer research Cytotoxic T cell IL-2 receptor |
| Zdroj: | Oncology Letters. 13:3781-3786 |
| ISSN: | 1792-1082 1792-1074 |
| DOI: | 10.3892/ol.2017.5933 |
| Popis: | Cytotoxic T lymphocyte antigen-4 (CTLA-4) is expressed during cluster of differentiation (CD)4+ T-cell activation and terminates immune responses by interrupting CD28-enhanced activation. In addition, CTLA-4 is known to be constitutively expressed in regulatory T-cells (Tregs) and to contribute to immune suppression by enhancing the suppressive function of Tregs. However, the molecular mechanisms underlying CTLA-4-mediated Treg suppression remains incompletely understood. Furthermore, it is uncertain whether the in vivo immune suppressive functions of CTLA-4 are mediated only by a reduction in the level of conventional T-cell activity, or enhancement of Treg function. The present study demonstrated that combination therapy with an anti-CTLA-4 monoclonal antibody and dendritic cell-mediated radioimmunotherapy (IR/DC) was able to promote an antitumor response and influence Treg function in a mouse model of lung cancer. Cell surface markers, including CTLA-4, CD25 and CD4, were analyzed using flow cytometry, and T-cell activities were measured using ELISPOT and cytotoxicity assays. It was revealed that anti-CTLA-4 combined treatment with IR/DC immunotherapy may execute a more powerful and effective anti-tumor immunity through the inhibition of Treg function. |
| Databáze: | OpenAIRE |
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