The Role of Cytotoxic and Regulatory T cells in Relapsed/Refractory Hodgkin Lymphoma

Koreishi, Aashiyana F.; Saenz, Adam J.; Persky, Dan O.; Cui, Hayan; Moskowitz, Allison; Moskowitz, Craig H.; Teruya‐Feldstein, Julie

doi:10.1097/pai.0b013e3181c7138b

Cited by 39 publications

(31 citation statements)

References 28 publications

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“…In this scenario, the malignant B cells would be susceptible to regulation by CD4 + T cells and Tregs. The last hypothesis is supported by several independent studies demonstrating a better survival of patients with B‐cell lymphoma who have a high number of FoxP3 + cells within the tumour 30–38 . Interestingly, several B‐cell malignancies have been linked to autoimmune diseases.…”

Section: Discussionmentioning

confidence: 82%

Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

et al. 2011

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Summary Cytotoxic CD4+ T cells have been found in patients with chronic lymphocytic leukaemia (CLL) and seem to be involved in the regulation of malignant B cells. The CD4+ T regulatory cells (Tregs) can regulate various immune cells, including B cells, by inducing their apoptosis. Hence, different subgroups of CD4+ T cells may be involved in the regulation of malignant B cells. In this study, the cytotoxic phenotype and function of various CD4+ T‐cell subgroups were investigated in patients with B‐cell malignancies. Peripheral blood was collected from patients with CLL, various B‐cell lymphomas, healthy adult donors, children with precursor B‐cell acute lymphoblastic leukaemia (pre‐B ALL) and from healthy children. CD4+ T cells (CD3+ CD4+ FoxP3−), Tregs (CD3+ CD4+ CD127low FoxP3+) and CD127high FoxP3+ T cells (CD3+ CD4+ CD127high FoxP3+) were analysed for their expression of the cytolytic markers CD107a and Fas ligand. Patients with CLL had increased CD107a expression on all tested T‐cell subgroups compared with healthy donors. Similar results were found in patients with B‐cell lymphomas whereas the CD107a expression in children with pre‐B ALL was no different from that in healthy controls. Fas ligand expression was similar between patient cells and cells of healthy donors. CD4+ T cells and Tregs from patients with CLL and healthy donors were subsequently purified and cultured in vitro with autologous B cells. Both subgroups lysed B cells and killing was confirmed by granzyme ELISAs. In conclusion, cytotoxic populations of CD4+ T cells, including Tregs, are present in patients with B‐cell malignancy and may be an important factor in immune‐related disease control.

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Section: Discussionmentioning

confidence: 82%

Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

et al. 2011

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“…4,14,15 Conversely, a higher proportion of regulatory T cells in the CHL microenvironment appears to confer a better prognosis. [16][17][18] The models for these interactions and their relevance to prognosis, however, have been based on cases of sporadic CHL. [18][19][20] Analysis of the cases in this series demonstrated that most cases of immunodeficiency-associated CHL display a predominance of CD163 + histiocytes (ratio of CD163 + /CD68 + cells, 0.66 to 2.8), consistent with an M2 phenotype, 4,21 and high numbers of T-regulatory FOX-P3 lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

“…[16][17][18] The models for these interactions and their relevance to prognosis, however, have been based on cases of sporadic CHL. [18][19][20] Analysis of the cases in this series demonstrated that most cases of immunodeficiency-associated CHL display a predominance of CD163 + histiocytes (ratio of CD163 + /CD68 + cells, 0.66 to 2.8), consistent with an M2 phenotype, 4,21 and high numbers of T-regulatory FOX-P3 lymphocytes. The average number and proportions of CD3 and FOX-P3 lymphocytes in our cases was significantly higher than that reported in cases of CHL not associated with immunodeficiency, 16,17 suggesting differences in pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Classical Hodgkin Lymphoma Arising in the Setting of Iatrogenic Immunodeficiency

Loo

Medeiros²,

Aladily³

et al. 2013

American Journal of Surgical Pathology

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Iatrogenic immunodeficiency-associated lymphoproliferative disorders are rare. A small subset of these lesions resembles classical Hodgkin lymphoma (CHL), but there are few data in the literature about these lesions. We describe 10 patients with autoimmune diseases treated with immunomodulator therapeutic agents who developed CHL. The autoimmune diseases included rheumatoid arthritis (n=5), systemic lupus erythematosus (n=2), dermatomyositis (n=1), autoimmune hepatitis (n=1), and Crohn disease (n=1), and the immunomodulatory therapies were methotrexate, azathioprine, tumor necrosis factor-α inhibitors, and thalidomide alone or in various combinations. The study group included 9 women and 1 man with a median age of 50 years (range, 25 to 77 y). The histologic features supported CHL in all cases with Reed-Sternberg (RS) and Hodgkin (H) cells in an inflammatory cell background, although the neoplasm could only be subclassified in 3 patients: 2 nodular sclerosis and 1 mixed cellularity. Immunohistochemical analysis supported the diagnosis of CHL. In all cases the RS-H cells were CD30. Nine of 10 cases were CD15, whereas CD20 was expressed variably in 4/10 cases. CD45/LCA was negative in 8 cases assessed. In situ hybridization for Epstein-Barr virus-encoded RNA was positive in the RS-H cells in 8/10 cases. The microenvironment of these lesions depicted a predominance of T-regulatory cells and M2 histiocytes. Clinical follow-up data were available for 7 patients, with a median posttreatment period of 27 months (range, 12 mo to 7 y). In all 7 patients immunomodulatory drug therapy was discontinued, and chemotherapy for CHL was administered; 2 patients also received local radiation. All 7 patients achieved complete remission and are alive. We conclude that iatrogenic immunodeficiency-associated CHL is highly associated with Epstein-Barr virus infection, and patients usually have a good outcome after discontinuation of immunomodulatory agents and chemotherapy for CHL.

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“…High numbers of Tregs in the TME correlate with worse prognosis in many types of cancer (Bates et al, 2006;Curiel et al, 2004;Hiraoka et al, 2006). Tregs can also be tumor suppressive as in some B cell cancers; their presence in Hodgkin's Lymphoma correlates with a good prognosis, presumably through a direct suppression of tumor cell growth (Fozza and Longinotti, 2011;Koreishi et al, 2010;Tzankov et al, 2008).…”

Section: T Lymphocytesmentioning

confidence: 99%

The tumor microenvironment at a glance

Balkwill

Capasso

Hagemann

2012

Journal of Cell Science

1,549

1,154

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The Role of Cytotoxic and Regulatory T cells in Relapsed/Refractory Hodgkin Lymphoma

Cited by 39 publications

References 28 publications

Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

Classical Hodgkin Lymphoma Arising in the Setting of Iatrogenic Immunodeficiency

The tumor microenvironment at a glance

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The Role of Cytotoxic and Regulatory T cells in Relapsed/Refractory Hodgkin Lymphoma

Cited by 39 publications

References 28 publications

Both CD4+ FoxP3+ and CD4+ FoxP3− T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

Both CD4+ FoxP3+ and CD4+ FoxP3− T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

Classical Hodgkin Lymphoma Arising in the Setting of Iatrogenic Immunodeficiency

The tumor microenvironment at a glance

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Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro

Both CD4⁺ FoxP3⁺ and CD4⁺ FoxP3⁻ T cells from patients with B‐cell malignancy express cytolytic markers and kill autologous leukaemic B cells in vitro