Regulatory (FOXP3+) T cells as target for immune therapy of cervical intraepithelial neoplasia and cervical cancer
| Autor: | Udo Baron, Harald Stein, Corinna Hoffmann, Sven Olek, Achim Schneider, Christoph Loddenkemper, Andreas M. Kaufmann, Joerg-Peter Ritz, Jochen Huehn, Günter Cichon, Dirk Nagorsen, Jonas Stanke |
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| Rok vydání: | 2009 |
| Předmět: |
CD4-Positive T-Lymphocytes
Cancer Research CD3 Complex T-Lymphocytes medicine.medical_treatment Transplantation Heterologous Uterine Cervical Neoplasms chemical and pharmacologic phenomena Receptors Nerve Growth Factor CD8-Positive T-Lymphocytes Cervical intraepithelial neoplasia T-Lymphocytes Regulatory Receptors Tumor Necrosis Factor Targeted therapy Mice Lymphocytes Tumor-Infiltrating Immune system Antigen Antigens CD Glucocorticoid-Induced TNFR-Related Protein medicine Animals Humans Cervical cancer business.industry Papillomavirus Infections Antibodies Monoclonal FOXP3 Cancer Forkhead Transcription Factors hemic and immune systems General Medicine Immunotherapy DNA Methylation Uterine Cervical Dysplasia medicine.disease Oncology Immunology Female business |
| Zdroj: | Cancer Science. 100:1112-1117 |
| ISSN: | 1349-7006 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2009.01153.x |
| Popis: | Regulatory (FOXP3+) T cells (Tregs) comprise a subpopulation of CD4+ T cells that suppress autoreactive immune cells, thereby protecting organs and tissues from autoimmunity. Tregs have also been detected in human malignancies and their depletion or inactivation substantially improves cellular antitumor immunity in preclinical studies. Novel therapeutic strategies for cervical cancer and precancerous cervical intraepithelial neoplasia (CIN) focus on immune-modulatory and cancer vaccination approaches. In this context, the frequency of Tregs in cervical cancer and precancerous CIN could influence therapeutic strategies. We determined the frequency of infiltrating CD4+ and CD8+ T cells as well as FOXP3+ Tregs in high-grade CIN lesions (CIN III) and cervical carcinoma compared to colon carcinoma, skin melanoma, and bronchial carcinoma. We show that human papilloma virus-derived lesions have a significantly higher number of infiltrating lymphocytes and FOXP3+ Tregs compared to three other common tumor entities. In addition we explored the therapeutic effect of agonistic anti-glucocorticoid-induced tumor necrosis factor receptor family-related protein antibodies that, by single systemic application, inactivate Tregs and induce strong intratumoral invasion of CD8+ T cells and complete tumor eradication in 70% of treated animals. The large number of Tregs in human papilloma virus-derived lesions suggests a pivotal role of Tregs for counteracting the host immune response. We therefore regard CIN and cervical cancer as prime targets for new immune-based non-invasive therapies. |
| Databáze: | OpenAIRE |
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