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Journal home Advance online publication Current issue Archive Press releases Supplements Focuses Guide to authors Online submission For referees Free online issue Contact the journal Subscribe Advertising work@npg Reprints and permissions About this site For librarians   NPG Resources Nature Nature Reviews Nature Immunology Nature Cell Biology Nature Genetics news@nature.com Nature Conferences Dissect Medicine NPG Subject areas Biotechnology Cancer Chemistry Clinical Medicine Dentistry Development Drug Discovery Earth Sciences Evolution & Ecology Genetics Immunology Materials Science Medical Research Microbiology Molecular Cell Biology Neuroscience Pharmacology Physics Browse all publications Article Nature Medicine  9, 1377 - 1382 (2003) Published online: 5 October 2003; | doi:10.1038/nm942 Ex vivo identification, isolation and analysis of tumor-cytolytic T cells Valerie Rubio1, Tor B Stuge1, Naileshni Singh1, Michael R Betts2, Jeffrey S Weber3, Mario Roederer4 & Peter P Lee1 1  Department of Medicine, Stanford University, 269 Campus Drive, Stanford, California 94305, USA. 2  Laboratory of Immunology, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, Maryland 20892, USA. 3  Norris Cancer Center, University of Southern California, 1441 Eastlake Avenue, Suite 3454, Los Angeles, California 90033, USA. 4  ImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, Maryland 20892, USA. Correspondence should be addressed to Peter P Lee ppl@stanford.eduWe isolated pure, viable populations of tumor-cytolytic T cells directly from patient blood samples using flow cytometric quantification of the surface mobilization of CD107a—an integral membrane protein in cytolytic granules—as a marker for degranulation after tumor stimulation. We show that tumor-cytolytic T cells are indeed elicited in patients after cancer vaccination, and that tumor reactivity is strongly correlated with efficient T-cell recognition of peptide-bearing targets. We combined CD107a mobilization with peptide−major histocompatibility complex (P-MHC) tetramer staining to directly correlate antigen specificity and cytolytic ability on a single-cell level. This showed that tumor-cytolytic T cells with high recognition efficiency represent only a minority of peptide-specific T cells elicited in patients after heteroclitic peptide vaccination. We were also able to expand these cells to high numbers ex vivo while maintaining their cytolytic potential. These techniques will be useful not only for immune monitoring of cancer vaccine trials, but also for adoptive cellular immunotherapy after ex vivo expansion. The ability to rapidly identify and isolate tumor-cytolytic T cells would be very useful in cancer immunotherapy. MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated RESEARCH Human dendritic cells genetically engineered to express cytosolically retained fragment of prostate-specific membrane antigen prime cytotoxic T-cell responses to multiple epitopes Cancer Gene Therapy Original Article (01 Dec 2003) Loss of inhibitor of apoptosis proteins as a determinant of polyamine analog-induced apoptosis in human melanoma cells Oncogene Original Article (07 Aug 2003) Induction of human cytotoxic T lymphocytes by artificial antigen-presenting cells Nature Biotechnology Research (01 Apr 2000)  Top Abstract Previous | Next Table of contents Full text Download PDF Send to a friend Open Innovation Challenges Direct Molecular Detection of Proteins and Nucleic Acids Deadline: Dec 02 2009 Reward: $5,000 USD This Challenge is looking for novel approaches to protein and nucleic acid detection. This is an Id... Novel Approaches to Protecting Maize from Insect Damage Deadline: Jan 31 2010 Reward: $20,000 USD The Seeker is looking for novel approaches to protecting maize from insect damage. This Challenge re... More Challenges Powered by: nature jobs Faculty Positions University of Texas Medical Branch Galveston, TX United States Medical Writer Cactus Global Mumbai 400053 India More science jobs Post a job for free Figures & Tables Supplementary info Export citation Search buyers guide:   ADVERTISEMENT

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