Cooperation of CD4+ T cells and CD8+ T cells and release of IFN-γ are critical for antileukemia responses of recipient mice treated by microtransplantation

Wang, Li; Du, Fang; Wang, Hongxiang; Xie, Conghua

doi:10.3892/etm.2017.5541

Cited by 6 publications

(5 citation statements)

References 31 publications

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“…After HMGB1 binds to the cell surface TLR4 receptor, intracellular signalling to the NF-κB complex degrades the IκB protein, releases active NF-κB p65 into the nucleus, and regulates gene transcription of the in ammatory factors IL-1β, IL-6 and TNF-α. A mouse model of autoimmune myocarditis showed improved cardiac function and reduced myocardial brosis after injection of HMGB1 antagonist [25].Yao et al attenuated doxorubicin-induced myocardial injury by blocking the in ammatory effects induced by hmgb1 [26].Wang et al found that HMGB1 in myocardial ischemia promotes in ammatory injury through targeting of TLR4 to promote in ammatory injury, and knockdown of TLR4 attenuated HMGB1-induced injury [27]. In contrast, according to Ma et al[28], the use of tlr4 blockers ampli es in ammation, inhibits autophagy, and exacerbates adriamycin-induced heart failure and brosis.…”

Section: Discussionmentioning

confidence: 99%

Radiation combined with PD-1 inhibitor induces time-dependent changes in myocardial injury by regulating HMGB1-associated inflammatory microenvironment

Liu,

Wu,

Wang

et al. 2024

Preprint

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Background PD-1 inhibitors may superimpose the toxicity of radiotherapy while increasing the antitumor effect. However, there are fewer studies on immune myocarditis caused by radiotherapy plus anti-PD-1 and the mechanism is still under exploration. Methods 40 C57BL/6 mice were randomly assigned to 4 groups. A: Control, B: PD-1 inhibitor, C: cardiac irradiation and D: thoracic irradiation + PD-1 inhibitor, mice were treated with either anti-PD-1 antibody with or without thoracic radiation (15Gy). Each group contained ten mice, five of which were studied for a duration of 1 month and the remaining five for 3 months. Tunel staining was utilized to observe apoptosis of cardiac tissues; histological analysis was performed to analyze the structural and morphological alterations, fibrosis of the heart tissue. The infiltration of CD3+, CD4+, and CD8 + T-cells into the cardiac was analyzed through flow cytometry; Elisa measured the expression levels of TNF-α, IL-1β, and TLR-4 in the cardiac; and immunoprotein blotting and qPCR were used to observe the protein and mRNA expression levels of HMGB1, TLR-4, and NF-κB p65. Results Group D exhibited a greater degree of cardiac injury, fibrosis, and apoptosis in comparison to groups A, B, and C. Additionally, there was an increase in injury, AI, and CVF values after three months as opposed to one month (P < 0.05).After one month, there was no statistically significant difference in cardiac damage, AI, or CVF values between groups A and B; however, after three months, there was a significant difference (P < 0.05). Group D also had higher levels of IL-1β, IL-6, TNF-α and T-lymphocyte distribution, HMGB1, TLR4, NF-κB P65 protein, and mRNA expression than the other three groups. However, each group's index expression declined over the course of three months as opposed to one month, and this difference was statistically significant (P < 0.05). Conclusion PD-1 inhibitors exacerbated myocardial injury based on radiation by upregulating the expression of inflammatory factors in the HMGB1 signaling pathway. In the early stages of myocardial damage, inflammatory alterations predominated, while in the later stages, fibrosis.

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Section: Discussionmentioning

confidence: 99%

Radiation combined with PD-1 inhibitor induces time-dependent changes in myocardial injury by regulating HMGB1-associated inflammatory microenvironment

Liu,

Wu,

Wang

et al. 2024

Preprint

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“…Yao et al demonstrated that blocking the in ammatory effects induced by HMGB1 can attenuate doxorubicin-induced myocardial injury [23]. Wang et al found that HMGB1 promotes in ammatory injury in myocardial ischemia by targeting TLR4, and knockdown of TLR4 can attenuate HMGB1-induced injury [24]. In contrast, Ma et al reported that the application of TLR4 blockers can amplify in ammation, inhibit autophagy, and worsen adriamycin-induced heart failure and brosis [25].…”

Section: Discussionmentioning

confidence: 99%

Cardiac irradiation combined with an anti-Programmed cell death protein 1 antibody induces time-dependent myocardial injury by regulating the HMGB1/NF-κB pathway

Liu,

Wu,

Wang

et al. 2024

Preprint

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Purpose Programmed cell death protein 1 (PD-1) inhibitors may further increase the risk of cardiotoxicity of radiotherapy while improving the outcomes of locally advanced lung cancer. However, few studies have focused on cardiac injury caused by radiotherapy plus anti-PD-1 therapy, and the underlying mechanism is still under exploration. This study aimed to explore this mechanism. Methods Six- to eight-week-old C57BL/6 mice were treated with either an anti-PD-1 antibody or phosphate-buffered saline (PBS) with or without 15 Gray (Gy) cardiac irradiation (IR). Five mice were sacrificed at 1 month, and the remaining mice were sacrificed at 3 months. Histological analysis was performed to determine the structural and morphological alterations and cardiac fibrosis. The infiltration of cardiac T cells was analysed via flow cytometry, and western blotting and qPCR were used to detect the protein and mRNA expression levels of HMGB1-related pathway. Results Group D (IR + anti-PD-1) demonstrated more severe injury, fibrosis, and apoptosis compared to groups A (control), B (anti-PD-1), and C (IR). Furthermore, the injury observed in Group D was significantly more severe, with higher values of apoptotic index (AI) and fibrotic area at 3 months compared to 1 month (P < 0.05). At 1 month, there were no significant differences in cardiac damage or AI or CVF values between groups A and B, but these differences emerged at 3 months (P < 0.05). Group D exhibited greater infiltration of T lymphocytes and increased expression of high mobility group box-1 protein (HMGB1), Toll-like receptor 4 (TLR4), and nuclear factor kappa-B (NF-κB P65) at both 1 and 3 months compared to the other three groups. Conclusion In combination with radiation, PD-1 inhibitors exacerbated myocardial injury by modulating the HMGB1/NF-κB signalling pathway.

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“…Microchimerism was reported to be a potential reason for MST antileukaemia [33,34] . Additionally, an MST mouse model demonstrated that G-PBSC infusion might stimulate recipient-derived T-cell responses for indirect antitumour effects [35] . However, one patient in our study developed serious acute GVHD and died of multiorgan failure.…”

Section: Discussionmentioning

confidence: 99%

Microtransplantation improves the outcome of older patients with newly diagnosed acute myeloid leukaemia: a single-centre study with long-term follow-up

Liang¹,

Huang²,

Yang³

et al. 2022

Preprint

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This retrospective single-centre study was to validate the efficacy and safety of microtransplantation in the treatment of older patients with acute myeloid leukemia (AML). Microtransplantation combines chemotherapy and human leukocyte antigen (HLA)-mismatched peripheral blood stem cell infusion without graft-versus-host disease (GVHD) prophylaxis. Totally, 26 newly diagnosed AML patients who received microtransplantation therapy were enrolled in our study from April 2008 to April 2018. The deadline date of follow-up was December 31, 2019. Patients were divided into 2 age groups: 60 ~ 70 years (n = 17) and > 70 years (n = 9). The study analyzed the data of complete remission (CR) rate, overall survival (OS), leukemia free survival (LFS), hematopoietic recovery time, and treatment related toxicities. 10 patients were still alive with complete remission (CR) on the deadline date, and the median overall survival (OS) was 64 months. The CR, relapse and nonrelapse mortality rates were 84.6%, 38.5% and 30%, respectively. Both OS (p < 0.0001) and leukaemia free survival (LFS) (p < 0.0001) were significantly higher in the younger group than in the older group. The median times of neutrophil and platelet recovery were 12 days and 14 days, respectively. These data showed that MST could be an alternative treatment for older AML patients.

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Cooperation of CD4+ T cells and CD8+ T cells and release of IFN-γ are critical for antileukemia responses of recipient mice treated by microtransplantation

Cited by 6 publications

References 31 publications

Radiation combined with PD-1 inhibitor induces time-dependent changes in myocardial injury by regulating HMGB1-associated inflammatory microenvironment

Radiation combined with PD-1 inhibitor induces time-dependent changes in myocardial injury by regulating HMGB1-associated inflammatory microenvironment

Cardiac irradiation combined with an anti-Programmed cell death protein 1 antibody induces time-dependent myocardial injury by regulating the HMGB1/NF-κB pathway

Microtransplantation improves the outcome of older patients with newly diagnosed acute myeloid leukaemia: a single-centre study with long-term follow-up

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