Peripheral blood regulatory<scp>T</scp>cell levels are correlated with some poor prognostic markers in newly diagnosed lymphoma patients

Gündüz, Eren; Sermet, Serap; Musmul, Ahmet

doi:10.1002/cyto.b.21330

Cited by 15 publications

(14 citation statements)

References 31 publications

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“…Thus far, published data on the levels of circulating Treg cells in newly diagnosed patients with NHL have yielded conflicting results. While some studies reported that the pre-therapy levels of Treg cells in patients with B-cell NHL are higher in PB compared with those of healthy individuals, other studies reported the opposite, or no association (12)(13)(14)(15)(16)(17). In the present study, the levels of circulating Treg cells tended to be lower in patients compared with healthy controls prior to the initiation of rituximab-based treatment, but their levels were markedly increased after CR.…”

Section: Discussioncontrasting

confidence: 63%

“…One of the objectives of the present study was to evaluate the interrelationships among the regulatory cell subsets, as these cells are known to interact with each other to establish a potent immunoregulatory environment to control tumor growth. Associations among circulating regulatory cell subsets and standard disease markers in patients with B-cell NHL has been evaluated by few studies with conflicting results (12)(13)(14)(15)(16)(17)20). The findings of the present study revealed that the levels of circulating Treg cells were not significantly correlated with Breg or iNKT cells, either pre-or post-rituximab-based therapy.…”

Section: Discussioncontrasting

confidence: 61%

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Levels of regulatory T cells and invariant natural killer cells and their associations with regulatory B�cells in patients with non-Hodgkin lymphoma

et al. 2018

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Due to their immunoregulatory properties, several specialized cell subsets, including regulatory T (Treg), invariant natural killer T (iNKT) and regulatory B (Breg) cells, are involved in the pathogenesis of non-Hodgkin lymphoma (NHL). However, the interaction between various cells remains to be elucidated. The aim of the present study was to evaluate the levels of Treg, iNKT and Breg cell subsets and their interrelationships in the peripheral blood (PB) and bone marrow (BM) of patients with B-cell NHL who received rituximab-based regimens and achieved a complete remission. A total of 20 patients and 20 healthy age-and sex-matched controls were prospectively enrolled for investigation of Treg, iNKT and Breg cell subsets in PB and BM by flow cytometry and cell culture. Prior to administration of combination chemotherapy with rituximab, the patients had lower levels of Breg cells and, to a lesser degree, Treg cells, but not iNKT cells, in PB compared with controls. Compartmental differences in the levels of Treg and Breg cell subsets, but not iNKT cells, were observed between PB and BM, suggesting an increase in trafficking through the blood of these regulatory cell subsets to the marrow. Following complete remission, the levels of circulating Treg, iNKT and Breg cell subsets increased. The levels of Treg cells were not significantly associated with iNKT and Breg cell subsets, although negative correlations were observed. Taken together, these results may provide new insights into the potential role of regulatory cell subsets in patients with B-cell NHL. However, whether the observed differences between PB and BM may affect clinical outcomes requires further investigation.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussioncontrasting

confidence: 61%

Levels of regulatory T cells and invariant natural killer cells and their associations with regulatory B�cells in patients with non-Hodgkin lymphoma

et al. 2018

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“…43 The manipulation of these suppressor cells has become the focus of attention as Tregs are significantly increased in peripheral blood of NHL patients receiving or not chemotherapy 44 and have been associated with a poor prognosis. 26 Different strategies have been developed to reduce the toxic side effects of IL-2 and its capacity to activate negative immune regulators. The generation of IL-2 variants able to expand preferentially immune effector cells has been explored.…”

Section: Discussionmentioning

confidence: 99%

A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy

et al. 2020

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Anti-CD20 treatment represents a therapeutic benefit for patients with B-cell lymphomas, although more efficient therapies are needed for refractory or relapsing patients. Among them, the combination of anti-CD20 and IL-2 that induces T cell response has been hampered by the expansion of FoxP3 + Tregs that strongly express the high affinity IL-2 receptor (IL-2R αβγ). We explore here the anti-tumor effect of an anti-CD20 antibody combined with a mutated IL-2 (no-alpha mutein) which has a disrupted affinity for the IL-2R αβγ. We demonstrate that anti-CD20/no-alpha mutein combination significantly augments the survival rate of mice challenged with huCD20 + cells as compared to animals treated with anti-CD20 ± IL-2. Moreover, the combination with no-alpha mutein but not IL-2 provokes an increase of granzyme B and perforin in splenic NK and CD8 + T cells, a reduction of Tregs and an increase in activated macrophages. The former combination also induces a T helper profile different from that obtained with IL-2, with an earlier polarization to Th1 and no increase in Th17. The therapeutic effect of anti-CD20/noalpha mutein was accompanied by an expansion of peripheral central (TCM) and effector (TEM) memory CD8 + T cell compartments. Last, as opposed to IL-2, no-alpha mutein administered at the beginning of anti-CD20 treatment did not dampen the long-term protection of surviving mice after tumor rechallenge. Thus, this study shows that the combination of anti-tumor antibodies and no-alpha mutein is a promising approach to improve the therapeutic effect of these antibodies by potentiating NK/macrophagemediated innate immunity and the adaptive T-cell response.

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“…The above-studied cohorts were similar (Europeans,~60 years), however direct comparison of the results cannot be totally correct due to variations in applied methodology: (1) calculation of Treg percentages in total population of PBMCs [100] or blood cells [99]; and (2) different definition of Treg phenotypes. Some studies on lymphoma patients have similarly found no variation in Treg levels in comparison to healthy volunteers [101,102], while others reported several-fold difference regardless of nationality, age and disease status (newly diagnosed vs. relapsed) [102][103][104].…”

Section: Treg Subsets May Be Overrepresented In Peripheral Blood Of Pmentioning

confidence: 99%

Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment

Titov

Valiullina

Zmievskaya

et al. 2020

Cancers

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Chimeric antigen receptor (CAR) immunotherapy is one of the most promising modern approaches for the treatment of cancer. To date only two CAR T-cell products, Kymriah® and Yescarta®, have been approved by the Food and Drug Administration (FDA) for the treatment of lymphoblastic leukemia and B-cell lymphoma. Administration of CAR T-cells to control solid tumors has long been envisaged as one of the most difficult therapeutic tasks. The first two clinical trials conducted in sarcoma and neuroblastoma patients showed clinical benefits of CAR T-cells, yet multiple obstacles still hold us back from having accessible and efficient therapy. Why did such an effective treatment for relapsed and refractory hematological malignancies demonstrate only relatively modest efficiency in the context of solid tumors? Is it due to the lucky selection of the “magic” CD19 antigen, which might be one of a kind? Or do lymphomas lack the immunosuppressive features of solid tumors? Here we review the existing knowledge in the field of CAR T-cell therapy and address the heterogeneity of solid tumors and their diverse strategies of immunoevasion. We also provide an insight into prospective developments of CAR T-cell technologies against solid tumors.

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Peripheral blood regulatoryTcell levels are correlated with some poor prognostic markers in newly diagnosed lymphoma patients

Cited by 15 publications

References 31 publications

Levels of regulatory T cells and invariant natural killer cells and their associations with regulatory B�cells in patients with non-Hodgkin lymphoma

Levels of regulatory T cells and invariant natural killer cells and their associations with regulatory B�cells in patients with non-Hodgkin lymphoma

A rationally-engineered IL-2 improves the antitumor effect of anti-CD20 therapy

Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment

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