Targeting HMGB1: An available Therapeutic Strategy for Breast Cancer Therapy

Dong, Haonan; Zhang, Lu; Liu, Suling

doi:10.7150/ijbs.73504

Cited by 31 publications

(21 citation statements)

References 150 publications

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“…ICD refers to the activation of the immune response during cell death through the transformation of non-immunogenic tumor cells to immunogenic ones. HMGB1 is one of the main markers of ICD that plays a role in dendritic cell maturation and antigen presentation to cytotoxic T cells (Dong, et al, 2022). HMGB1 released by dead tumor cells will bind to the TLR4 receptor on dendritic cells and cause antigen cross-presentation on tumor cells (Apetoh, et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…This indicates that HMGB1 expression affects the maturation process of dendritic cells so that they can present tumor cell antigens. CD8+ receptors on T cells will then recognize these tumor cell antigens (Dong, et al, 2022). Exposure to an electric field was able to induce the release of the cytokine HMGB1 in rat breast tumors as a marker of ICD, suggesting that cell death due to exposure to electric fields is immunogenic.…”

Section: Discussionmentioning

confidence: 99%

“…HMGB1 is expressed by the cells during stress or by the dead cells. HMGB1 plays a role in dendritic cell maturation and antigen presentation to cytotoxic T cells (Dong, et al, 2022). HMGB1 blockade in breast tumors causes a drastic decrease in T lymphocytes (Hubert, et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats

Fathurrohmah¹,

Cahyadi²,

Alamsyah³

et al. 2022

Indones J Cancer Chemoprevent

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Electro Capacitive Cancer Therapy (ECCT) is an electric field-based cancer therapy method using intermediate frequency (150 kHz) and low intensity (18 Vpp). High Mobility Group Box 1 (HMGB1) is a cytokine related to damage-associated molecular patterns (DAMPs) secreted by dead cells. The expression of Programmed Death Ligand 1 (PD-L1) is ligand present on the surface of tumor cells and its expression is associated with the increase in the number CD8+ T lymphocytes. This study aims to examine the effect of ECCT exposure on the expression of HMGB1 and PD-L1 genes on the breast tumor, brain, and liver tissues of Rattus norvegicus (Berkenhout, 1769). The tissues were obtained from the previous studies stored in RNAlater (-20˚C). Female rat tissues of the previous study from four treatment groups, namely the control group (NINT), non-DMBA-induction with therapy (NIT), DMBA-induction with non-therapy (INT), and DMBA-induction with therapy (IT). Gene expression was analyzed using the RT-qPCR. Statistical t-test with a p<0.05 significance level was performed using GraphPad Prism 9.4.0 software. The result shows HMGB1 and PD-L1 mRNA genes were both significantly expressed in breast tumor samples. The liver and brain samples of normal rats did not show any significant changes in the activity of these genes after exposure to the electric field. This study indicates that exposure to electric fields may trigger the expression of HMGB1 and PD-L on the rat’s breast tumor samples. This study also provides information related to the safety of ECCT in healthy organs of female rats, especially the brain and liver.Keywords: ECCT, breast tumor, HMGB1, PD-L1, IFN- γ.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats

Fathurrohmah¹,

Cahyadi²,

Alamsyah³

et al. 2022

Indones J Cancer Chemoprevent

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“…SOM230 is currently used in clinical trials [142,161]. Consistently, immune signals such as HMGB1 are widely recognized to induce autophagy [162] and promote phosphorylation of Bcl-2 and dissociation of Beclin1-Bcl-2 through the ERK pathway [163]. As a result, the three major autophagy pathways play vital roles in the dual function of autophagy in anticancer therapies and may be applied in clinical settings when the autophagy pathway is manipulated in an appropriate manner.…”

Section: The Pivotal Roles Of Autophagy In Cancer Therapymentioning

confidence: 99%

Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy

Wu¹,

Chen²,

Chiu³

et al. 2023

Theranostics

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Immunotherapies are now emerging as an efficient anticancer therapeutic strategy. Cancer immunotherapy utilizes the host's immune system to fight against cancer cells and has gained increasing interest due to its durable efficacy and low toxicity compared to traditional antitumor treatments, such as chemotherapy and radiotherapy (RT). Although the combination of RT and immunotherapy has drawn extensive attention in the clinical setting, the overall response rates are still low. Therefore, strategies for further improvement are urgently needed. Nanotechnology has been used in cancer immunotherapy and RT to target not only cancer cells but also the tumor microenvironment (TME), thereby helping to generate a long-term immune response. Nanomaterials can be an effective delivery system and a strong autophagy inducer, with the ability to elevate autophagy to very high levels. Interestingly, autophagy could play a critical role in optimal immune function, mediating cell-extrinsic homeostatic effects through the regulation of danger signaling in neoplastic cells under immunogenic chemotherapy and/or RT. In this review, we summarize the preclinical and clinical development of the combination of immunotherapy and RT in cancer therapy and highlight the latest progress in nanotechnology for augmenting the anticancer effects of immunotherapy and RT. The underlying mechanisms of nanomaterial-triggered autophagy in tumor cells and the TME are discussed in depth. Finally, we suggest the implications of these three strategies combined together to achieve the goal of maximizing the therapeutic advantages of cancer therapy and show recent advances in biomarkers for tumor response in the evaluation of those therapies.

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“…HMGB1 has three conserved cysteine residues at positions 23, 45, and 106 ( 12 ). HMGB1 is a damage-associated molecular pattern protein involved in several disease states, including cancer ( 13 ), arthritis ( 14 ), and sepsis ( 15 ); it also acts as a late mediator in endotoxemia. HMGB1 is actively secreted by monocytes and macrophages after stimulation with microbes or proinflammatory cytokines ( 11 ).…”

Section: Introductionmentioning

confidence: 99%

The HMGB1 (C106A) mutation inhibits IL-10-producing CD19hiFcγRIIbhi B cell expansion by suppressing STAT3 activation in mice

et al. 2022

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Regulatory B cells have important roles in inflammation and autoimmune diseases. A newly discovered subpopulation of B cells with a CD19hiFcγRIIbhi phenotype inhibits the proliferation of CD4+ T cells by secreting interleukin (IL)-10. The expansion of CD19hiFcγRIIbhi B cells in mouse spleen can be induced by lipopolysaccharide (LPS) or CpG oligodeoxynucleotide stimulation. However, the mechanism of CD19hiFcγRIIbhi B cell expansion and its role in inflammatory diseases are unclear. Here, we report that, under inflammatory conditions, the proliferation and immunosuppressive function of CD19hiFcγRIIbhi B cells were decreased in high mobility group box1 (HMGB1) C106A mutant mice, compared with wild-type mice. The HMGB1 (C106A) mutation in B cells reduced STAT3 phosphorylation, restricting the expansion and suppressive function of CD19hiFcγRIIbhi B cells. Compared with CD19hiFcγRIIbhi B cells from wild-type mice, CD19hiFcγRIIbhi B cells from Hmgb1(C106A) mice significantly reduced the survival of mice with sepsis. Recombinant HMGB1 promoted the expansion of IL-10-producing CD19hiFcγRIIbhi B cells among LPS-activated B cells in vitro. Furthermore, the percentage of CD19hiFcγRIIbhi regulatory B cells in the peripheral blood was increased in patients with sepsis, compared with healthy controls. These findings implicate the role of HMGB1 in the expansion and immunosuppressive function of CD19hiFcγRIIbhi B cells.

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Targeting HMGB1: An available Therapeutic Strategy for Breast Cancer Therapy

Cited by 31 publications

References 150 publications

Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats

Electric Field-Based Cancer Therapy Induces the Expression of HMGB1 and PD-L1 mRNA Genes on Breast Tumor of Female Rats

Nanoparticles augment the therapeutic window of RT and immunotherapy for treating cancers: pivotal role of autophagy

The HMGB1 (C106A) mutation inhibits IL-10-producing CD19hiFcγRIIbhi B cell expansion by suppressing STAT3 activation in mice

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