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Tumor-specific CD4+ Melanoma Tumor-infiltrating Lymphocytes.
MedLine Citation:
PMID:  22576345     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  JOURNAL ARTICLE     Date:  2012-5-8
Journal Detail:
Title:  Journal of immunotherapy (Hagerstown, Md. : 1997)     Volume:  -     ISSN:  1537-4513     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9706083     Medline TA:  J Immunother     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
*Surgery Branch, National Cancer Institute, NIH, Bethesda, MD †Department of Surgery, Yale University, New Haven, CT.
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