GARP-mediated active TGF-β1 induces bone marrow NK cell dysfunction in AML patients with early relapse post–allo-HSCT

Wang, Dongyao; Sun, Zimin; Zhu, Xiaoyu; Zheng, Xiaohu; Zhou, Yonggang; Lu, Yichen; Yan, Peidong; Wang, Huiru; Liu, Huilan; Jin, Jing; Zhu, Huaqing; Sun, Rui; Wang, Yi; Fu, Binqing; Tian, Zhigang; Wei, Haiming

doi:10.1182/blood.2022015474

Cited by 28 publications

(18 citation statements)

References 52 publications

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“…[40] Within the first year after HSCT, the IR of CD4 + , CD8 + T, and NK cells protects against various infections and maintains the graft-versus-leukemia (GVL) effect. [41,42] Our results showed that CD8 + T and NK cells rapidly returned to their normal levels after UCBT. UCBT preserved the strong GVL effect, possibly because of the rapid reconstitution of CD8 + T and NK cells; this finding is consistent with the results of the randomized controlled trial by Appelbaum, in which the cumulative incidence of relapse was lower in patients after UCBT.…”

Section: Discussionmentioning

confidence: 69%

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Pan,

Ding,

Huang

et al. 2023

Chinese Medical Journal

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Background: With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation (UCBT), the correlation between immune reconstitution (IR) after UCBT and graft-versus-host disease (GVHD) has been reported successively, but reports on double-negative T (DNT) cell reconstitution and its association with acute GVHD (aGVHD) after UCBT are lacking. Methods: A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology, the First Affiliated Hospital of USTC, between August 2018 and June 2021. IR differences were compared between the patients with and without aGVHD. Results: The absolute number of DNT cells in the healthy Chinese population was 109 (70–157)/μL, accounting for 5.82 (3.98–8.19)% of lymphocytes. DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation. Importantly, the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year (F = 4.684, P = 0.039 and F = 5.583, P = 0.026, respectively). In addition, the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased, and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD (HR = 0.46, 95% confidence interval [CI]: 0.23–0.93; P = 0.031). Conclusions: Compared to the number of DNT cells in Chinese healthy people, the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow. In addition, the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.

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Section: Discussionmentioning

confidence: 69%

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Pan,

Ding,

Huang

et al. 2023

Chinese Medical Journal

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“…UCBT group showed significantly increased numbers of highly activated NK cells NK cells are the first subpopulation of lymphocytes that are reconstituted after HSCT, and play a key role in GVL and other immune responses (13). Therefore, we characterized NK-cell reconstitution after HSCT by analyzing the immature CD56brightCD16− NK cells and mature CD56dimCD16+ NK cells.…”

Section: Ucbt Group Showed Increased Proportion Of Highly Active Cd8 ...mentioning

confidence: 99%

“…Differences in the immune reconstitution are expected between UCBT and PBSCT because they represent two diverse sources of HSCs and progenitor cells. Therefore, the success of the allo-HSCT treatment is dependent on the incidence of GVL effects exerted by the donor CD4 + T cells, CD8 + T cells, and NK cells during the immune cell reconstitution process post-transplantation ( 13 – 15 ). PES, ES, and aGVHD are the most common immune responses during the early stages post-HSCT ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Dynamic comparison of early immune reactions and immune cell reconstitution after umbilical cord blood transplantation and peripheral blood stem cell transplantation

et al. 2023

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Umbilical cord blood transplantation (UCBT) and peripheral blood stem cell transplantation (PBSCT) are effective allogeneic treatments for patients with malignant and non-malignant refractory hematological diseases. However, the differences in the immune cell reconstitution and the immune reactions during initial stages post-transplantation are not well established between UCBT and PBSCT. Therefore, in this study, we analyzed the differences in the immune reactions during the early stages (days 7-100 post-transplantation) such as pre-engraftment syndrome (PES), engraftment syndrome (ES), and acute graft-versus-host disease (aGVHD) and the immune cell reconstitution between the UCBT and the PBSCT group of patients. We enrolled a cohort of patients that underwent UCBT or PBSCT and healthy controls (n=25 each) and evaluated their peripheral blood mononuclear cell (PBMC) samples and plasma cytokine (IL-10 and GM-CSF) levels using flow cytometry and ELISA, respectively. Our results showed that the incidences of early immune reactions such as PES, ES, and aGVHD were significantly higher in the UCBT group compared to the PBSCT group. Furthermore, in comparison with the PBSCT group, the UCBT group showed higher proportion and numbers of naïve CD4+ T cells, lower proportion and numbers of Tregs, higher proportion of CD8+ T cells with increased activity, and higher proportion of mature CD56dim CD16+ NK cells during the early stages post-transplantation. Moreover, the plasma levels of GM-CSF were significantly higher in the UCBT group compared to the PBSCT group in the third week after transplantation. Overall, our findings demonstrated significant differences in the post-transplantation immune cell reconstitution between the UCBT and the PBSCT group of patients. These characteristics were associated with significant differences between the UCBT and the PBSCT groups regarding the incidences of immune reactions during the early stages post transplantation.

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“…In addition, Benechet et al found that naïve HBV-specific CD8 + T cells primed by infected hepatocytes could not differentiate into interferon (IFN)-γ-expressing effector T cells in an HBV transgenic mouse model [ 65 ]. Tregs and macrophages may also contribute to the immunosuppressive environment through the production of immunomodulatory cytokines such as interleukin (IL)-10 and tumor growth factor (TGF)-β1 [ 39 , 66 , 67 ]. Furthermore, myeloid-derived suppressor cells (MDSC) in the liver microenvironment were shown to suppress T cell signaling partially through the production of arginase, which could degrade arginine and significantly inhibit T cell effector function [ 68 , 69 , 70 ].…”

Section: Mechanisms Of Hbv Immune Evasionmentioning

confidence: 99%

Advances in Immunotherapy for Hepatitis B

Wang

Wei

2022

Pathogens

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Hepatitis B virus (HBV) is a hepatotropic virus with the potential to cause chronic infection, and it is one of the common causes of liver disease worldwide. Chronic HBV infection leads to liver cirrhosis and, ultimately, hepatocellular carcinoma (HCC). The persistence of covalently closed circular DNA (cccDNA) and the impaired immune response in patients with chronic hepatitis B (CHB) has been studied over the past few decades. Despite advances in the etiology of HBV and the development of potent virus-suppressing regimens, a cure for HBV has not been found. Both the innate and adaptive branches of immunity contribute to viral eradication. However, immune exhaustion and evasion have been demonstrated during CHB infection, although our understanding of the mechanism is still evolving. Recently, the successful use of an antiviral drug for hepatitis C has greatly encouraged the search for a cure for hepatitis B, which likely requires an approach focused on improving the antiviral immune response. In this review, we discuss our current knowledge of the immunopathogenic mechanisms and immunobiology of HBV infection. In addition, we touch upon why the existing therapeutic approaches may not achieve the goal of a functional cure. We also propose how combinations of new drugs, and especially novel immunotherapies, contribute to HBV clearance.

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GARP-mediated active TGF-β1 induces bone marrow NK cell dysfunction in AML patients with early relapse post–allo-HSCT

Cited by 28 publications

References 52 publications

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Reconstitution of double-negative T cells after cord blood transplantation and its predictive value for acute graft-versus-host disease

Dynamic comparison of early immune reactions and immune cell reconstitution after umbilical cord blood transplantation and peripheral blood stem cell transplantation

Advances in Immunotherapy for Hepatitis B

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