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Tumor‐infiltrating lymphocytes isolated from a Ki‐1–positive large cell lymphoma of the skin. Phenotypic characterization and analysis of cytokine secretion
Author(s) -
Reinhold Uwe,
Abken Hinrich,
Kukel Sylvia,
Goeden Barbara,
Uerlich Manfred,
Neumann Ute,
Kreysel HansWilhelm
Publication year - 1991
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19911115)68:10<2155::aid-cncr2820681012>3.0.co;2-y
Subject(s) - biology , cd8 , cytotoxic t cell , microbiology and biotechnology , interleukin 2 , clone (java method) , t lymphocyte , il 2 receptor , t cell , antigen , cd3 , t cell receptor , tumor infiltrating lymphocytes , tumor necrosis factor alpha , cytokine , immunology , in vitro , immune system , gene , biochemistry
Tumor‐infiltrating lymphocytes (TIL) were obtained from a biopsy of a patient with a Ki‐1–positive large cell lymphoma of the skin. Immunohistologic studies of the large anaplastic tumor cells showed an “aberrant” T “helper/inducer” phenotype (CD30+CD3–CD4+CD8–IL–2R+HLA–DR+). Using a cDNA probe for the constant region of the T‐cell receptor (TCR) beta gene, the cells were identified by their distinct monoclonal rearrangement of T‐cell receptor (TCR)‐beta DNA. Tumor cells isolated from biopsies were cultured in the presence of interleukin‐2 (IL‐2). Outgrowing lymphocytes were cloned, expanded in vitro , and 11 clones were subjected to phenotypic analysis: ten clones showed a predominantly CD4‐positive T “helper/inducer” phenotype whereas one clone expressed CD8 T “cytotoxic/suppressor” antigens. In contrast to the tumor cells, cells of all clones grown in vitro expressed the TCR‐associated CD3 complex. Furthermore, cells from all clones analyzed expressed CD5, CD7, CD45RO (UCHL1), CD11a (LFA‐1), CD25, and HLA‐DR antigens. Cells of two of ten CD4‐positive clones expressed CD45RA (2H4) in addition to UCHL1. T‐cell clones isolated from the tumor and grown in vitro exhibited individual DNA restriction band patterns different from that of a DNA tumor biopsy specimen. Therefore, the authors conclude that these T‐cell clones represent presumably nonmalignant TIL. All clones tested secreted interferon (IFN)‐gamma and tumor necrosis factor (TNF)‐alpha in vitro . Nine of 11 clones were found to secrete additionally IL‐2 and IL‐4 upon stimulation with phytohemagglutinin (PHA) whereas two clones did not secrete detectable amounts of IL‐4. Selective growth of TIL in the presence of IL‐2 opens the possibility to use these cells in adoptive immunotherapy of cutaneous T‐cell lymphoma (CTCL). Cytokines secreted by TIL cells in vitro (IL‐2, IL‐4, IFN‐gamma, TNF‐alpha) may be involved in their antitumorgenic activity. Moreover, these data implicate that CD4‐positive TIL derived from CTCL cannot be grouped into different subsets based on the production of IL‐2, IL‐4, IFN‐gamma, and TNF‐alpha. 68:2155‐2160, 1991.