| Tumor-specific CD4+ Melanoma Tumor-infiltrating Lymphocytes. | |
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MedLine Citation:
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PMID: 22576345 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) can mediate objective and durable tumor regressions in patients with metastatic melanoma. CD8 tumor-reactive TIL are well studied in humans and animals, yet the function of tumor-infiltrating CD4 T lymphocytes in patient treatments remains controversial. We recently demonstrated that CD4 TILs are not necessary for objective responses in patients. Coinfusion with tumor-specific CD4 TIL may enhance or increase the durability of tumor regressions, but the number of patients with tumor-reactive CD4 TIL is unknown. We screened 44 CD8-depleted TIL for in vitro reactivity against autologous tumor. Nine (20%) showed specific reactivity by interferon-γ release assay, of which 8 were specifically blocked by an anti-HLA-DR antibody. Flow-cytometric analysis of these reactive TIL confirmed a high CD4 composition (median 89%). Highlighting the contribution of CD4 TIL to tumor regression, a patient with widespread metastatic disease was administered TIL containing HLA class II-restricted tumor activity with high-dose interleukin-2 therapy after lymphodepletion that mediated regression of extensive metastatic disease in the liver and spleen. These results demonstrate that at least 20% of metastatic melanomas contain CD4 lymphocytes with specific tumor recognition and suggest a possible role for CD4 cells in the effectiveness of adoptive cell therapy. |
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Authors:
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Kevin M Friedman; Peter A Prieto; Laura E Devillier; Colin A Gross; James C Yang; John R Wunderlich; Steven A Rosenberg; Mark E Dudley |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-5-8 |
Journal Detail:
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Title: Journal of immunotherapy (Hagerstown, Md. : 1997) Volume: - ISSN: 1537-4513 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-5-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9706083 Medline TA: J Immunother Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Surgery Branch, National Cancer Institute, NIH, Bethesda, MD †Department of Surgery, Yale University, New Haven, CT. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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