Expression pattern of T-cell–associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 685-690 ◽  
Author(s):  
Dan Jones ◽  
Carl O'Hara ◽  
Madeleine D. Kraus ◽  
Antonio R. Perez–Atayde ◽  
Aliakbar Shahsafaei ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Receptor Expression ◽  
Non Hodgkin Lymphoma ◽  
Alk Positive

Abstract Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes.

Expression pattern of T-cell–associated chemokine receptors and their chemokines correlates with specific subtypes of T-cell non-Hodgkin lymphoma

Blood ◽  
2000 ◽  
Vol 96 (2) ◽  
pp. 685-690 ◽  
Author(s):  
Dan Jones ◽  
Carl O'Hara ◽  
Madeleine D. Kraus ◽  
Antonio R. Perez–Atayde ◽  
Aliakbar Shahsafaei ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Receptor Expression ◽  
Non Hodgkin Lymphoma ◽  
Alk Positive

Chemokine receptors mediate the migration of lymphocytes through the binding of soluble ligands, and their expression is differentially regulated in lymphocyte subsets. The pattern of chemokine receptor expression in T-cell non-Hodgkin lymphoma has not been previously studied. Using a panel of mouse monoclonal antibodies, we studied the immunohistochemical expression of the Th1-associated chemokine receptor CXCR3 in 141 patients with T-cell lymphoma, and we studied the receptors CCR4 and CCR5 and some of their ligands in a subset of these tumors. Expression of CXCR3 was typical of the smaller T cells in angioimmunoblastic lymphoma (15 of 18 patients), angiocentric lymphoma (3 of 3 patients), histiocyte-rich tumors (4 of 5 patients), and unspecified T-cell lymphomas (17 of 39 patients). CXCR3 expression was seen in only 1 of 15 patients with anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma. In contrast, all ALK-positive tumors showed diffuse reactivity for the Th2-associated receptor CCR4 (5 of 5 patients). CCR4 expression was also a consistent feature of the large-cell transformation of mycosis fungoides. CCR5 expression showed no consistent association with any T-cell tumor type. The chemokines Mig (CXCR3 ligand), TARC (CCR4 ligand), and MCP-2 (CCR5 ligand) were detected in intratumoral blood vessels and histiocytes. Mig was also coexpressed by a subset of CXCR3-positive tumor cells in 6 of 20 lymphomas. MCP-2 was highly expressed in stromal cells in 3 patients with nodal involvement by cutaneous T-cell lymphoma. As with normal T-cell subsets, we demonstrated that there is frequent differential expression of chemokine receptors in T-cell tumors, which may explain, in part, the distinctive patterns of spread in different tumor subtypes.

Clinical Applications of the Genomic Landscape of Aggressive Non-Hodgkin Lymphoma

2017 ◽  
Vol 35 (9) ◽  
pp. 955-962 ◽  
Author(s):  
Andrea B. Moffitt ◽  
Sandeep S. Dave
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma ◽  
T Cell Lymphomas

In this review, we examine the genomic landscapes of lymphomas that arise from B, T, and natural killer cells. Lymphomas represent a striking spectrum of clinical behaviors. Although some lymphomas are curable with standard therapy, the majority of the affected patients succumb to their disease. Here, the genetic underpinnings of these heterogeneous entities are reviewed. We consider B-cell lymphomas, including Burkitt lymphoma, diffuse large B-cell lymphoma, Hodgkin lymphoma, and primary mediastinal B-cell lymphoma. We also examine T-cell lymphomas, including anaplastic large-cell lymphoma, angioimmunoblastic T-cell lymphoma, cutaneous T-cell lymphoma, adult T-cell leukemia/lymphoma, and other peripheral T-cell lymphomas. Together, these malignancies make up most lymphomas diagnosed around the world. Genomic technologies, including microarrays and next-generation sequencing, have enabled a better understanding of the molecular underpinnings of these cancers. We describe the broad genomics findings that characterize these lymphoma types and discuss new therapeutic opportunities that arise from these findings.

Treatment and prognosis of mature T-cell and NK-cell lymphoma: an analysis of patients with T-cell lymphoma treated in studies of the German High-Grade Non-Hodgkin Lymphoma Study Group

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3418-3425 ◽  
Author(s):  
Norbert Schmitz ◽  
Lorenz Trümper ◽  
Marita Ziepert ◽  
Maike Nickelsen ◽  
Anthony D. Ho ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Study Group ◽  
High Grade ◽  
Non Hodgkin Lymphoma ◽  
Large Cell Lymphoma ◽  
Alk Positive ◽  
Lymphoma Study Group

Abstract To evaluate outcome and prognosis of patients with T-cell lymphoma we analyzed 343 patients treated within trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Two hundred eighty-nine patients belonged to 1 of the 4 major T-cell lymphoma subtypes: anaplastic large cell lymphoma (ALCL), anaplastic large cell lymphoma kinase (ALK)–positive (n = 78); ALCL, ALK-negative (n = 113); peripheral T-cell lymphoma, unspecified (PTCLU; n = 70); and angioimmunoblastic T-cell lymphoma (AITL; n = 28). Treatment consisted of 6-8 courses of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone/prednisolone) or etoposide plus (CHOEP). Three-year event-free survival (EFS) and overall survival were 75.8% and 89.8% (ALK-positive ALCL), 50.0% and 67.5% (AITL), 45.7% and 62.1% (ALK-negative ALCL), and 41.1% and 53.9% (PTCLU), respectively. The International Prognostic Index (IPI) was effective in defining risk groups with significantly different outcomes. For patients, ≤ 60 years with lactate dehydrogenase ≤ upper normal value (UNV), etoposide improved improved 3-year EFS: 75.4% versus 51.0%, P = .003. In patients > 60 years 6 courses of CHOP administered every 3 weeks remains the standard therapy. Patients with ALK-negative ALCL, PTCLU, or AITL presenting with IPI > 1 have a poor prognosis and should be considered candidates for novel treatment strategies.

scholarly journals An Update in Management of Noncutaneous T-Cell Lymphomas

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Y. Y. Hwang ◽  
R. H. S. Liang
Keyword(s):  
T Cell ◽  
Treatment Approach ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Conventional Chemotherapy ◽  
High Dose Therapy ◽  
T Cell Lymphomas ◽  
Alk Positive

T-cell lymphoma is a heterogeneous group of diseases. Except for ALK positive anaplastic large cell lymphoma, T-cell lymphoma responds to conventional chemotherapy unfavourably, and most patients carry poor prognosis. In recent years, efforts have been made to improve the outcome of T-cell lymphoma patients. Novel agents, high-dose therapy, and allogeneic stem cell transplantation are studied, and various results are reported in literature. This paper looks into the prognostication and treatment approach of different entities of noncutaneous T-cell lymphoma and would focus on the latest updates in its management.

scholarly journals Imaging of Chemokine Receptor-4 Targeted PET/CT with 68Ga-Pentixafor in Non-Hodgkin Lymphoma: Comparison to 18F-FDG

2020 ◽  
Author(s):  
Qingqing Pan ◽  
Yaping Luo ◽  
Yan Zhang ◽  
Long Chang ◽  
Ji Li ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Lymphoplasmacytic Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Pet Ct

Abstract Background: In order to study the CXCR4 expression with 68Ga-Pentixafor PET in different types of non-Hodgkin lymphoma, we performed a retrospective study to describe the 68Ga-Pentixafor PET/CT imaging in a spectrum of lymphomas and to compare it with 18F-FDG PET/CT. Results: Twenty-seven patients with newly diagnosed non-Hodgkin lymphoma were recruited retrospectively. 68Ga-Pentixafor PET showed increased radioactivity in lymphoplasmacytic lymphoma (n = 8), marginal zone lymphoma (n = 4), diffuse large B cell lymphoma (n = 3), follicular lymphoma (n = 2), mantle cell lymphoma (n = 1), unclassified indolent B cell lymphoma (n = 3) and enteropathy associated T cell lymphoma (n = 3). However, peripheral T cell lymphoma, not otherwise specified (n = 1), and NK/T cell lymphoma (n = 2) were not avid for 68Ga-Pentixafor. In comparison to 18F-FDG PET, 68Ga-Pentixafor PET demonstrated more extensive disease and higher radioactivity in lymphoplasmacytic lymphoma and marginal zone lymphoma. Conclusion: CXCR4 expression varies in different types of non-Hodgkin lymphoma. Overexpression of CXCR4 was detected with 68Ga-Pentixafor PET/CT in lymphoplasmacytic lymphoma, marginal zone lymphoma, diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, unclassified indolent B cell lymphoma, and enteropathy associated T cell lymphoma.

Response to brentuximab vedotin by CD30 expression: Results from five trials in PTCL, CTCL, and B-cell lymphomas.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 7543-7543
Author(s):  
Deepa Jagadeesh ◽  
Steven M. Horwitz ◽  
Nancy L. Bartlett ◽  
Ranjana H. Advani ◽  
Eric D. Jacobsen ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
Antibody Drug Conjugate ◽  
Non Hodgkin Lymphoma

7543 Background: Brentuximab vedotin (BV), an antibody-drug conjugate targeting CD30, has been evaluated in multiple trials in patients (pts) with peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), or B-cell lymphoma. We examined the ability of CD30 expression level to predict response to BV across these patient populations. Methods: Data were integrated from 275 pts with PTCL, CTCL, and B-cell lymphoma treated with BV from 5 prospective clinical trials. Study SGN35-012 evaluated BV plus rituximab or BV monotherapy in pts with relapsed/refractory non-Hodgkin lymphoma. The ALCANZA study compared BV to physician’s choice of methotrexate or bexarotene in pts with mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL). Three investigator-sponsored trials evaluated BV monotherapy in pts with relapsed PTCL, MF, and pcALCL (35-IST-030, 35-IST-001, 35-IST-002). Exploratory analyses were conducted to examine the relationship between CD30 expression and objective response rate (ORR) for pts with CD30 expression ≥10%, <10%, or undetectable (0%) by IHC (malignant cells or lymphoid infiltrate; local review). Results: 143 pts had tumors with CD30 <10%, including 58/143 with undetectable CD30. Activity with BV was observed at all levels of CD30 expression, including CD30=0 (Table). Analysis of the interaction between CD30 and duration of response is ongoing and will be presented in the final poster. ORR by CD30 expression, n/N (%). Clinical trial information: NCT01421667, NCT02588651, NCT01578499, NCT01352520, NCT01396070. Conclusions: CD30 expression levels ≥10%, <10%, or undetectable did not predict response to BV in a range of CD30-expressing lymphomas: Clinical responses occurred in pts with CD30 low and CD30 undetectable lymphomas. Limitations of IHC, the dynamic nature and heterogeneity of cell-surface CD30 expression, and multiple mechanisms of action of BV may all contribute to this observation.[Table: see text]

Small nucleolar RNA expression profiling identifies potential prognostic markers in peripheral T-cell lymphoma

Blood ◽  
2012 ◽  
Vol 120 (19) ◽  
pp. 3997-4005 ◽  
Author(s):  
Wilfried Valleron ◽  
Loic Ysebaert ◽  
Laure Berquet ◽  
Virginie Fataccioli ◽  
Cathy Quelen ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Expression Profiles ◽  
Prognostic Significance ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Not Otherwise Specified ◽  
Rna Expression Profiling

Abstract Peripheral T-cell lymphoma (PTCL) is a rare, heterogeneous type of non-Hodgkin lymphoma (NHL) that, in general, is associated with a poor clinical outcome. Therefore, a current major challenge is the discovery of new prognostic tools for this disease. In the present study, a cohort of 122 patients with PTCL was collected from a multicentric T-cell lymphoma consortium (TENOMIC). We analyzed the expression of 80 small nucleolar RNAs (snoRNAs) using high-throughput quantitative PCR. We demonstrate that snoRNA expression analysis may be useful in both the diagnosis of some subtypes of PTCL and the prognostication of both PTCL-not otherwise specified (PTCL-NOS; n = 26) and angio-immunoblastic T-cell lymphoma (AITL; n = 46) patients treated with chemotherapy. Like miRNAs, snoRNAs are globally down-regulated in tumor cells compared with their normal counterparts. In the present study, the snoRNA signature was robust enough to differentiate anaplastic large cell lymphoma (n = 32) from other PTCLs. For PTCL-NOS and AITL, we obtained 2 distinct prognostic signatures with a reduced set of 3 genes. Of particular interest was the prognostic value of HBII-239 snoRNA, which was significantly over-expressed in cases of AITL and PTCL-NOS that had favorable outcomes. Our results suggest that snoRNA expression profiles may have a diagnostic and prognostic significance for PTCL, offering new tools for patient care and follow-up.

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