Document Detail

Autologous tumor infiltrating T cells cytotoxic for follicular lymphoma cells can be expanded in vitro.
MedLine Citation:
PMID:  9160688     Owner:  NLM     Status:  MEDLINE    
Follicular lymphomas (FLs) rarely induce clinically significant T-cell-mediated responses. We showed that freshly isolated tumor infiltrating T cells (T-TILs) lack tumor-specific cytotoxicity. Stimulation of these T cells with FL cells in the presence of interleukin-2 (IL-2) and/or costimulation via CD28 does not lead to T-cell activation and expansion. In contrast, when stimulated with FL cells preactivated via CD40, autologous T-TILs can be expanded by the addition of exogenous IL-2. These T cells can be further expanded in vitro by the addition of exogenous IL-4, IL-7, or interferon-gamma, but not IL-12. Once activated, these T cells showed FL-directed cytotoxicity in four of five patients tested. We concluded that autologous cytotoxic anti-FL-specific T cells exist, but can only be detected in vitro under optimized conditions for T-cell stimulation and expansion. This suggests that their frequency in vivo is either very low or that the microenvironment does not provide the necessary signals to activate these T cells. This model system allows dissection of the requisite conditions for activation and expansion of lymphoma-directed cytotoxicity and may permit expansion of previously activated cytotoxic T cells for adoptive transfer.
J L Schultze; M J Seamon; S Michalak; J G Gribben; L M Nadler
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Blood     Volume:  89     ISSN:  0006-4971     ISO Abbreviation:  Blood     Publication Date:  1997 May 
Date Detail:
Created Date:  1997-06-19     Completed Date:  1997-06-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3806-16     Citation Subset:  AIM; IM    
Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
B-Lymphocytes / immunology,  pathology
Cells, Cultured
Chromosomes, Human, Pair 14 / ultrastructure
Chromosomes, Human, Pair 18 / ultrastructure
Cytotoxicity, Immunologic
Interferon-gamma / pharmacology
Interleukin-12 / pharmacology
Interleukin-2 / pharmacology
Interleukin-4 / pharmacology
Interleukin-7 / pharmacology
Lymphocyte Activation / drug effects
Lymphocytes, Tumor-Infiltrating / drug effects,  immunology,  pathology*
Lymphoma, Follicular / pathology*
Neoplastic Stem Cells / immunology,  pathology
T-Lymphocytes, Cytotoxic / drug effects,  pathology*
Translocation, Genetic
Reg. No./Substance:
0/Interleukin-2; 0/Interleukin-7; 187348-17-0/Interleukin-12; 207137-56-2/Interleukin-4; 82115-62-6/Interferon-gamma

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