Increase of Circulating CD4+CD25highFoxp3+ Regulatory T Cells in Patients With Metastatic Renal Cell Carcinoma During Treatment With Dendritic Cell Vaccination and Low-Dose Interleukin-2
| Autor: | Per thor Straten, Annika Berntsen, Marie Klinge Brimnes, Inge Marie Svane |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Interleukin 2 Cancer Research medicine.medical_treatment Immunology chemical and pharmacologic phenomena Cancer Vaccines T-Lymphocytes Regulatory Immune tolerance Interleukin 21 Humans Immunology and Allergy Medicine IL-2 receptor Neoplasm Metastasis Antigen-presenting cell Carcinoma Renal Cell Cells Cultured Aged Cell Proliferation Pharmacology business.industry Interleukins Interleukin-2 Receptor alpha Subunit FOXP3 Forkhead Transcription Factors hemic and immune systems Dendritic Cells Immunotherapy Dendritic cell Middle Aged Coculture Techniques CD4 Antigens Disease Progression Interleukin-2 Female business medicine.drug |
| Zdroj: | Journal of Immunotherapy. 33:425-434 |
| ISSN: | 1524-9557 |
| Popis: | Regulatory T cells (Treg) play an important role in the maintenance of immune tolerance and may be one of the obstacles of successful tumor immunotherapy. In this study, we analyzed the impact of administration of dendritic cell (DC) vaccination in combination with low-dose interleukin (IL)-2 in patients with metastatic renal cell carcinoma on the frequency of CD4 + CD25 high Foxp3 + Treg cells in peripheral blood. We found that the treatment increased the frequency of Treg cells more than 7-fold compared with pretreatment levels (P < 0.0001). The frequency of Treg cells decreased when patients had been off IL-2 treatment for only 8 days, but remained higher than pretreatment levels. A functional assay showed that isolated Treg cells were capable of inhibiting proliferation of responder cells. Also, in vitro studies showed that coculture of mature DCs, autologous T cells and IL-2 leads to an increase in the number of Treg cells whereas IL-21 does not stimulate the induction of Treg cells. These findings demonstrate that even low doses of IL-2 in combination with DC vaccination are able to expand CD4 + CD25 + Foxp3 + Treg cells in vivo in metastatic renal cell carcinoma patients. Further, the results indicate that the IL-2-induced effect on Treg cells is reversible and declines shortly after termination of IL-2 treatment. Our data suggest that approaches combining DC-mediated immunotherapy and depletion of Treg cells may be necessary to enhance the ability of vaccination therapy to elicit effective antitumor responses in cancer patients. Also, adjuvant IL-21 administration may lead to immune enhancement without simultaneous induction of Treg cells. |
| Databáze: | OpenAIRE |
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