| Autor: |
Larsen SK; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark ; These authors contributed equally to this work., Ahmad SM; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark ; These authors contributed equally to this work., Idorn M; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark., Met Ö; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark., Martinenaite E; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark., Svane IM; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark., Straten PT; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark., Andersen MH; Center for Cancer Immune Therapy (CCIT); Department of Hematology; Copenhagen University Hospital ; Herlev ; Herlev, Denmark. |
| Jazyk: |
angličtina |
| Zdroj: |
Oncoimmunology [Oncoimmunology] 2014 Nov 14; Vol. 3 (8), pp. e953411. Date of Electronic Publication: 2014 Nov 14 (Print Publication: 2014). |
| DOI: |
10.4161/21624011.2014.953411 |
| Abstrakt: |
In the present study, we describe forkhead box O3 (FOXO3)-specific, cytotoxic CD8 + T cells existent among peripheral-blood mononuclear cells (PBMCs) of cancer patients. FOXO3 immunogenicity appears specific, as we did not detect reactivity toward FOXO3 among T cells in healthy individuals. FOXO3 may naturally serve as a target antigen for tumor-reactive T cells as it is frequently over-expressed in cancer cells. In addition, expression of FOXO3 plays a critical role in immunosuppression mediated by tumor-associated dendritic cells (TADCs). Indeed, FOXO3-specific cytotoxic T lymphocytes (CTLs) were able to specifically recognize and kill both FOXO3-expressing cancer cells as well as dendritic cells. Thus, FOXO3 was processed and presented by HLA-A2 on the cell surface of both immune cells and cancer cells. As FOXO3 programs TADCs to become tolerogenic, FOXO3 signaling thereby comprises a significant immunosuppressive mechanism, such that FOXO3 targeting by means of specific T cells is an attractive clinical therapy to boost anticancer immunity. In addition, the natural occurrence of FOXO3-specific CTLs in the periphery suggests that these T cells hold a function in the complex network of immune regulation in cancer patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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