γ/δ Receptor-expressing T-cell clones from a cutaneous T-cell lymphoma suppress hematopoiesis

1992 ◽  
Vol 65 (3) ◽  
pp. 111-115 ◽  
Author(s):  
M. Wilhelm ◽  
P. Meyer ◽  
C. Batram ◽  
H. P. Tony ◽  
R. Dummer ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Clones ◽  
Cell Clones

T-cell-clones from lesional skin of cutaneous T-cell-lymphoma express functional CD95

1998 ◽  
Vol 16 ◽  
pp. S53
Author(s):  
R. Englert ◽  
S. Harwix ◽  
Th. Jung ◽  
K. Reich ◽  
Ch. Neumann
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Clones ◽  
Lesional Skin ◽  
Cell Clones

Isolation of Tumor-Specific Cytotoxic CD4+ and CD4+CD8dim+ T-Cell Clones Infiltrating a Cutaneous T-Cell Lymphoma

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4331-4341 ◽  
Author(s):  
Martine Bagot ◽  
Hamid Echchakir ◽  
Fathia Mami-Chouaib ◽  
Marie-Hélène Delfau-Larue ◽  
Dominique Charue ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Autologous Tumor ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Clones ◽  
Cell Clones

We have isolated several T-cell clones from lymphocytes infiltrating a human major histocompatibility class (MHC) II negative cutaneous T-cell lymphoma (CTCL). We describe here two of these clones, TC5 and TC7, with, respectively, a CD4+CD8dim+ and CD4+CD8− phenotype. Both clones mediated a specific MHC class I–restricted cytotoxic activity toward the fresh autologous tumor cells, and autologous tumor cell lines previously established with interleukin-2 (IL-2) and IL-7 from the skin and from the blood. Analysis of the T-cell receptor (TCR) Vβ gene expression showed that the tumor cells, which were shown to have a trisomy 7 by fluorescent in situ hybridization, expressed Vβ7/Jβ2.3, Vβ13/Jβ2.5, and Vβ22/Jβ2.5 rearrangements. Phenotypic analysis using specific anti-Vβ monoclonal antibodies indicated that only Vβ13 could be detected on the cell membrane of the tumor cells. Analysis of the TCR Vβ gene expression of the clones showed that TC5 and TC7 expressed a unique TCR-Vβ transcript, corresponding, respectively, to Vβ5/Jβ2.3 and Vβ17/Jβ2.7 gene segments. To determine whether these reactive T lymphocytes were present in vivo, we used specific primers corresponding to TC5- and TC7-Vβ TCR transcripts. The results showed that both cytotoxic T-cell clones were present at the lesional skin site and amplified in vitro. TC7 was found in the patient peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that the repertoire of the reactional lymphocytes differs in the blood and at the tumor site. These results show for the first time the presence of reactive T lymphocytes with CD4 or double-positive phenotype infiltrating a CTCL. These findings raise the question of the role of these antitumoral effector T cells in the tumor growth.

Isolation of Tumor-Specific Cytotoxic CD4+ and CD4+CD8dim+ T-Cell Clones Infiltrating a Cutaneous T-Cell Lymphoma

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4331-4341 ◽  
Author(s):  
Martine Bagot ◽  
Hamid Echchakir ◽  
Fathia Mami-Chouaib ◽  
Marie-Hélène Delfau-Larue ◽  
Dominique Charue ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Autologous Tumor ◽  
Cutaneous T Cell Lymphoma ◽  
T Cell Clones ◽  
Cell Clones

Abstract We have isolated several T-cell clones from lymphocytes infiltrating a human major histocompatibility class (MHC) II negative cutaneous T-cell lymphoma (CTCL). We describe here two of these clones, TC5 and TC7, with, respectively, a CD4+CD8dim+ and CD4+CD8− phenotype. Both clones mediated a specific MHC class I–restricted cytotoxic activity toward the fresh autologous tumor cells, and autologous tumor cell lines previously established with interleukin-2 (IL-2) and IL-7 from the skin and from the blood. Analysis of the T-cell receptor (TCR) Vβ gene expression showed that the tumor cells, which were shown to have a trisomy 7 by fluorescent in situ hybridization, expressed Vβ7/Jβ2.3, Vβ13/Jβ2.5, and Vβ22/Jβ2.5 rearrangements. Phenotypic analysis using specific anti-Vβ monoclonal antibodies indicated that only Vβ13 could be detected on the cell membrane of the tumor cells. Analysis of the TCR Vβ gene expression of the clones showed that TC5 and TC7 expressed a unique TCR-Vβ transcript, corresponding, respectively, to Vβ5/Jβ2.3 and Vβ17/Jβ2.7 gene segments. To determine whether these reactive T lymphocytes were present in vivo, we used specific primers corresponding to TC5- and TC7-Vβ TCR transcripts. The results showed that both cytotoxic T-cell clones were present at the lesional skin site and amplified in vitro. TC7 was found in the patient peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that the repertoire of the reactional lymphocytes differs in the blood and at the tumor site. These results show for the first time the presence of reactive T lymphocytes with CD4 or double-positive phenotype infiltrating a CTCL. These findings raise the question of the role of these antitumoral effector T cells in the tumor growth.

scholarly journals T-cell lymphoma secondary to checkpoint inhibitor therapy

2020 ◽  
Vol 8 (1) ◽  
pp. e000104 ◽  
Author(s):  
Kartik Anand ◽  
Joe Ensor ◽  
Sai Ravi Pingali ◽  
Patrick Hwu ◽  
Madeleine Duvic ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Immune Checkpoint ◽  
Cell Lymphoma ◽  
Checkpoint Inhibitors ◽  
T Cell Lymphoma ◽  
T Cell Clones ◽  
Cell Clones ◽  
Epithelial Origin ◽  
Pharmacovigilance Database

BackgroundMurine model suggests programmed cell death-1 (PD-1), an immune checkpoint not only plays role in tumor escape but is also a tumor suppressor for T-cells. But until, no reports of secondary T-cell lymphoma postuse of immune checkpoint inhibitors (ICIs) has been reported. Herein, we present a hitherto unreported phenomenon of secondary T-cell lymphoma when PD-1 inhibitor was used in a patient diagnosed with a tumor of epithelial origin.Case reportA man in mid-70s presented with biopsy-proven metastatic tumor of epithelial origin. Patient received carboplatin in combination with paclitaxel for four cycles leading to partial remission. The patient was subsequently switched to pembrolizumab due to persistent disease in the mediastinum. After four cycles of PD-1 inhibitor, patient presented with progression of disease and was diagnosed with biopsy-proven peripheral T-cell lymphoma-not otherwise specified. Based on the reported tumor suppressor function of PD-1 in murine models, we hypothesized that the use of PD-1 inhibitor caused clonal proliferation of abnormal T-cell clone leading to T-cell lymphoma. T-cell receptor (TCR) sequencing was performed by TCRβ sequencing and T-cell clones from pre-ICI treatment specimen were compared with post-ICI treatment specimens. We show that one of the T-cell clones present in pre-ICI treatment specimen at a low frequency of had massive expansion to become most dominant clone in post-ICI treatment specimens leading to lymphoma. Moreover, targeted exome sequencing revealed a new TET2 mutation in the clone representing the lymphoma.Next, we retrospectively reviewed the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), the pharmacovigilance database from 2012 to 2018 to find the reported incidence of this phenomenon and calculated the reporting OR (ROR) for disproportionality analysis for risk of T-cell lymphoma due to checkpoint inhibitors compared with other drugs. In FAERS, the incidence of T-cell lymphoma post-ICIs (pembrolizumab, nivolumab and ipilimumab) was found to be 0.02% with 17% mortality. The ROR probability of risk of T-cell lymphoma compared with other drugs in pharmacovigilance database was increased at 1.91.ConclusionsT-cell lymphoma is a rare sequela of ICIs with high mortality. Larger studies with long-term follow-up of patients receiving ICIs is needed.

scholarly journals Skin colonization by circulating neoplastic clones in cutaneous T-cell lymphoma

2019 ◽  
Author(s):  
Aishwarya Iyer ◽  
Dylan Hennessey ◽  
Sandra O’Keefe ◽  
Jordan Patterson ◽  
Weiwei Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cell ◽  
Cell Lymphoma ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Cell Fraction ◽  
Tumor Seeding ◽  
T Cell Clones ◽  
Cell Clones ◽  
Potential Biomarker

AbstractMycosis fungoides (MF) is a mature T-cell lymphoma currently thought to develop primarily in the skin by a clonal expansion of a transformed, resident memory T-cell. However, this concept does not explain the key characteristics of MF such as the debut with multiple, widespread skin lesions or inability of skin directed therapies to provide cure. The testable inference of the mature T-cell theory is the clonality of MF with respect to all rearranged T-cell receptor (TCR) genes. Here we have used whole exome sequencing approach to detect and quantify TCRα, -β and -γ clonotypes in tumor cell clusters microdissected from MF lesions. This method allows us to calculate the tumor cell fraction of the sample and therefore an unequivocal identification of the TCR clonotypes as neoplastic. Analysis of TCR sequences from 29 patients with MF stage I-IV proved existence of multiple T-cell clones within the tumor cell fraction, with a considerable variation between patients and between lesions from the same patient (median 11 clones, range 2-80 clones/sample). We have also detected multiple neoplastic clones in the peripheral blood in all examined patients. Based on these findings we propose that circulating neoplastic T-cell clones continuously replenish the lesions of MF thus increasing their heterogeneity by a mechanism analogous to the consecutive tumor seeding. We hypothesize that circulating neoplastic clones might be a promising target for therapy and could be exploited as a potential biomarker in MF.

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