دورية أكاديمية
Disease-associated Bias in T Helper Type 1 (Th1)/Th2 CD4+ T Cell Responses Against MAGE-6 in HLA-DRB10401+ Patients With Renal Cell Carcinoma or Melanoma
| العنوان: | Disease-associated Bias in T Helper Type 1 (Th1)/Th2 CD4+ T Cell Responses Against MAGE-6 in HLA-DRB10401+ Patients With Renal Cell Carcinoma or Melanoma |
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| المؤلفون: | Tatsumi, Tomohide, Kierstead, Lisa S., Ranieri, Elena, Gesualdo, Loreto, Schena, Francesco P., Finke, James H., Bukowski, Ronald M., Mueller-Berghaus, Jan, Kirkwood, John M., Kwok, William W., Storkus, Walter J. |
| المصدر: | The Journal of Experimental Medicine ; volume 196, issue 5, page 619-628 ; ISSN 1540-9538 0022-1007 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2002 |
| الوصف: | T helper type 1 (Th1)-type CD4+ antitumor T cell help appears critical to the induction and maintenance of antitumor cytotoxic T lymphocyte (CTL) responses in vivo. In contrast, Th2- or Th3/Tr-type CD4+ T cell responses may subvert Th1-type cell-mediated immunity, providing a microenvironment conducive to disease progression. We have recently identified helper T cell epitopes derived from the MAGE-6 gene product; a tumor-associated antigen expressed by most melanomas and renal cell carcinomas. In this study, we have assessed whether peripheral blood CD4+ T cells from human histocompatibility leukocyte antigens (HLA)-DRβ1*0401+ patients are Th1- or Th2-biased to MAGE-6 epitopes using interferon (IFN)-γ and interleukin (IL)-5 enzyme-linked immunospot assays, respectively. Strikingly, the vast majority of patients with active disease were highly-skewed toward Th2-type responses against MAGE-6–derived epitopes, regardless of their stage (stage I versus IV) of disease, but retained Th1-type responses against Epstein-Barr virus– or influenza-derived epitopes. In marked contrast, normal donors and cancer patients with no current evidence of disease tended to exhibit either mixed Th1/Th2 or strongly Th1-polarized responses to MAGE-6 peptides, respectively. CD4+ T cell secretion of IL-10 and transforming growth factor (TGF)-β1 against MAGE-6 peptides was not observed, suggesting that specific Th3/Tr-type CD4+ subsets were not common events in these patients. Our data suggest that immunotherapeutic approaches will likely have to overcome or complement systemic Th2-dominated, tumor-reactive CD4+ T cell responses to provide optimal clinical benefit. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1084/jem.20012142 |
| الإتاحة: | https://doi.org/10.1084/jem.20012142Test https://rupress.org/jem/article-pdf/196/5/619/1708428/jem1965619.pdfTest |
| رقم الانضمام: | edsbas.2EF489AE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1084/jem.20012142 |
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