TY - JOUR
T1 - Genotypic analysis of T-cell clones derived from cutaneous T-cell lymphoma lesions demonstrates selective growth of tumor-infiltrating lymphocytes
AU - Ho, Vincent C.
AU - Baadsgaard, Ole
AU - Elder, James T.
AU - Hansen, Erik R.
AU - Hanson, Curtis A.
AU - Vejlsgaard, Gunhild L.
AU - Cooper, Kevin D.
N1 - Funding Information:
uraneous T-celllymphoma (CTCL) is a malignancy of T cells that primarily affects the skin. Mycosis fungoides, rhe most common type of CTCL, is often characterized by a long latent period and an indolent C clintcal course [1]. Unlike most lymphomas, CTCL les10ns, even at a late stage. often contain a polymorphous infiltrate comprised not only of malignant T cells but also normal-appearing lymphocytes, macrophages, and other inflammatory cells. These unusual features of CTCL prompted us to begin ro address three questions: i) whether non-malignant, reactive T cells [so-called rumor mfiltratmg lymphocytes (TIL)] are present in lesions of Manuscnpt received June 20, I 989; accepted for publication March 16, 1990. Th1s work was supported m part by NIH grant #AROI 770-02 (KDC), by the Veterans Admm1stranon Medical Research Service (KDC), and by the BAbcock Foundauon QTE). Dr. Ho was a recipient of the R. Samuel McLaughlm Rc~earch Fellowsh1p from Canada during this study and is currently affiliated w1th the Umvermy of British Columbia, and the Bmish Columbia Cancer Agency, Vancouver, Canada. Thts work wa~ presented m part at the Soc1ety oflnvestiganve Dermatology Meetmg, WashmgtOn, DC, Apnl 1988. Reprmt requests to: Dr. Vincent C. Ho. D1vision of Dermatology. Univermy of Bnush Columb1a, 855 West lOth Avenue, Vancouver, B.C., Canada V5Z ll7. Abbrevm1ons: CTCL: cutaneous T cell lymphoma IJ...-2: mterleukm-2 LAK: lymphokme activated k1ller cells PHA: phytohernagluumn rlL-2: recombmam IL-2 TCR: T-cdl receptor Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T -cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy of CTCL. J Invest Derma col 9 5:4-8, 1990 CTCL; ii) whether these TIL can modulate the growth of the rumor cells; and iii) whether they can ultimately be harnessed to treat CTCL patients.
PY - 1990/7
Y1 - 1990/7
N2 - The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) β- and γ-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy of CTCL.
AB - The nature of T cells contained within cutaneous lesions of cutaneous T-cell lymphoma (CTCL) has not been studied at the clonal level. T cells extracted from skin lesions of two CTCL patients were cloned by limiting dilution and propagated in interleukin-2 (IL-2) containing medium with periodic lectin stimulation. Twelve T-cell clones were derived from each patient. In both cases, genotypic analysis of the T-cell clones revealed that these clones had T-cell receptor (TCR) β- and γ-chain gene rearrangements distinct from the predominant, presumably malignant, clone present in the skin, lymph nodes, or blood. This suggests that they were derived from presumably reactive (non-malignant) T cells. Furthermore, these clones had gene rearrangements different from each other, indicating their multiple clonal origins. The failure to propagate in vitro the CTCL T-cell clone suggests that CTCL cells may have growth requirements different from normal T cells. Thus, conventional T-cell culturing methods using IL-2 and lectins as mitogen may selectively propagate the presumably reactive T cells contained within the skin lesions. The ability to selectively grow these reactive lesional T cells (so-called tumor infiltrating lymphocytes) raises the possibility that these cells could be used in adoptive immunotherapy of CTCL.
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U2 - 10.1111/1523-1747.ep12872650
DO - 10.1111/1523-1747.ep12872650
M3 - Article
C2 - 2142183
AN - SCOPUS:0025310779
SN - 0022-202X
VL - 95
SP - 4
EP - 8
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 1
ER -