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

Boulassel, Mohamed-Rachid; Qarni, Zahra Al; Burney, Ikram A.; Khan, Hammad; Al-Zubaidi, Abeer; Naamani, Amal Al; Al-Hinai, Huda; Al-Badi, Amira; Qureshi, Rizwan; Panjwani, Vinodh; Farsi, Khalil Al

doi:10.3892/mco.2018.1732

Cited by 7 publications

(6 citation statements)

References 25 publications

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“…This result is consistent with results from previous studies that have reported that an increased proportion of Tregs in PBMC is a poor prognostic factor in DLBCL patients [ 15 , 45 ]. However, low concentrations of Tregs in PBMC have also been observed in DLBCL patients, generating some controversy that still needs to be clarified [ 46 , 47 ]. In our study, we also evaluated the effect of treatment on Treg levels.…”

Section: Discussionmentioning

confidence: 99%

Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape

Sun

et al. 2022

J Transl Med

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Background Regulatory T cells (Tregs) induce immune responses and may contribute to immune escape in tumors. Accumulation of Tregs in tumors represents a critical barrier to anti-tumor immunity and immunotherapy. However, conflicting results describing the role of Tregs in lymphoma warrant further investigation. The precise features and mechanisms underlying the alteration in Tregs in diffuse large B-cell lymphoma (DLBCL) are not well understood yet. In this study, we analyzed the mechanism underlying the observed alterations in Tregs in DLBCL and examined the effect of Lkb1 expression on the immunosuppressive function of human Tregs. Methods Flow cytometry and immunofluorescence were used to analyze the proportion of Tregs and effector Tregs in the peripheral blood and lymph nodes of patients with DLBCL and control group. In vitro culture assays were used to analyze the immunosuppressive function of Tregs in the two groups. Transcriptome sequencing was performed to analyze the differentially expressed genes in the two groups, and the transcription level and protein expression of Lkb1 in the two groups were detected using RT-PCR and WES microprotein technology. Lentiviral vectors were constructed to explore the functional changes of Tregs with stable upregulation and downregulation of Lkb1. Finally, a humanized murine lymphoma model was established to study the function of Lkb1 in Tregs in the pathogenesis of DLBCL. Results The number of Tregs was found to be dramatically increased in peripheral blood and tumor tissue in DLBCL patients compared with that in healthy controls, and decreased after treatment. Tregs from DLBCL patients exhibited multiple enhanced functions, including increased inhibition of CD8+cytotoxic T cells (CTL) against tumor cells, enhanced suppression of CD8+CTL secretion of granular enzyme, and suppression of CD8+CTL degranulation. Lkb1 was found to be upregulated in Tregs of DLBCL patients. Furthermore, Lkb1 contributes to Treg immunosuppressive function in DLBCL by regulating the mevalonate pathway. Finally, deletion of Lkb1 in Tregs suppressed tumor growth and promoted anti-tumor immunity in a DLBCL murine model. Conclusions These findings confirmed that Lkb1-regulated Tregs are critical for immune escape in DLBCL, which emphasizes that Lkb1 is a potential target for the immunotherapy of DLBCL.

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Section: Discussionmentioning

confidence: 99%

Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape

Sun

et al. 2022

J Transl Med

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“…In hematological convalescents, a reduced naïve and induced Treg population may lead to loss of suppressive function or an insufficient inflammatory response upon exposure to pathogens. This fact is particularly important in patients with lymphoid malignancies in whom function of CD4+, CD8+, and Treg cells is impaired due to the immunopathology of underlying disease and applied treatment 21,22 …”

Section: Discussionmentioning

confidence: 99%

Impaired adaptive immune response in COVID‐19 convalescent patients with hematological malignancies

Kalicińska

Szymczak

Andrasiak³

et al. 2022

European J of Haematology

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Objectives The immune dysregulation during SARS‐CoV‐2 has the potential to worsen immune homeostasis after recovery. Patients with hematological malignancies with COVID‐19 have changes both in the innate and adaptive immune responses. Little is known about the severity of immune dysfunction following recovery from COVID‐19 in hematological patients. Methods Here, we performed a comprehensive analysis of the lymphocyte subsets in peripheral blood mononuclear cells by FACS Canto II in 55 patients, including 42 with hematological malignancies 4–6 weeks after COVID‐19. Results Hematological COVID‐19 convalescents had deep reduction in CD3+ T cells, including helper T cells (CD3 + CD4+), naïve helper T cells (CD3 + CD4 + CD45RA+), and memory CD4+ T cells among with extremely low levels of Treg cells and decreased expression of both TCRα/β and TCRγ/δ. Severe immune dysregulation in hematological convalescents was expressed by increased activation of T lymphocytes, both as elevated levels of activated T cells (CD3 + HLA‐DR+) and activated cytotoxic T cells (CD3 + CD8 + HLA‐DR+). Conclusions Our findings showed a profound impairment of the adaptive immune response in hematological convalescents which might be a result of persistent activation of T cells. Convalescents with lymphoid malignancies showed more pronounced depletion of key T lymphocytes subpopulations in creating an effective adaptive response and immune memory.

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“…The level of Breg cells of patients with oesophageal carcinoma and gastric cancer was significantly higher than that in healthy controls [4,5]. Boulassel et al [20] found the levels of Breg cells were lower in patients with B cell non-Hodgkin lymphoma (NHL) compared with that of healthy controls, and the frequency of Breg cells was remarkably increased after R-CHOP chemotherapy. Previous research has shown that Breg cells promote human hepatocellular carcinoma (HCC) growth and invasiveness [6].…”

Section: Discussionmentioning

confidence: 99%

The Role of Regulatory B Cells in Patients with Acute Myeloid Leukemia

Wang

Liu

2019

Med Sci Monit

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Background Regulatory B (Breg) cells are a group of B cells with immunomodulatory function, which mainly exert negative immunomodulatory function by secreting IL-10 and other cytokines. Due to their immunoregulatory properties, Breg cells may participate in the pathogenesis of acute myeloid leukemia (AML). This study was designed to explore the frequency of Breg cells and the relationship between the Breg cells and clinical data in patients with AML. Material/Methods A total of 46 (36 in peripheral blood, 10 in bone marrow) AML patients and 15 healthy donors (HD) were included for detection of Breg cells frequency by multicolor flow cytometry. All cases were divided into different groups according to FAB subtypes of leukemia, white blood cell count (WBC) levels, age, cytogenetic characteristics, and molecular abnormalities, and were compared the differences of Breg cell frequency. Survival curve analysis was performed to estimate the value of Breg cell frequency in prognosis among cases with AML. Results We found that the frequency of Breg cells was higher in AML patients both in peripheral blood (PB) and in bone marrow (BM) compared with those in HDs. The AML patients with high WBC levels had higher Breg cell frequency compared with those with low WBC levels. Low-risk patients with had lower Breg cells frequency compared to the medium-risk patients. The patients with high WBC and high Breg cells frequency showed a shorter overall survival. Similarly, the overall survival of AML patients in the older group with high Breg cells frequency was significantly shorter than in the younger group with low Breg cell frequency. Conclusions For AML patients, the frequency of Breg cells was elevated, and high frequency of Breg cells may reveal poor prognosis.

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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

Cited by 7 publications

References 25 publications

Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape

Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape

Impaired adaptive immune response in COVID‐19 convalescent patients with hematological malignancies

The Role of Regulatory B Cells in Patients with Acute Myeloid Leukemia

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