Roles of HMGB1 in regulating myeloid-derived suppressor cells in the tumor microenvironment

Jin, Shuiling; Yang, Zhenzhen; Hao, Xin; Tang, Wenxue; Ma, Wei; Zong, Hong

doi:10.1186/s40364-020-00201-8

Cited by 36 publications

(22 citation statements)

References 74 publications

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“…The main alarmin, HMGB1, released by pyroptotic cells, could promote tumor cell survival, which largely suggests that HMGB1 drives the accumulation of MDSCs by inducing autophagy, thereby maintaining MDSC viability. 268 , 269 , 270 In addition, HMGB1 also enhances the immune suppression of MDSCs by promoting their differentiation from bone marrow progenitor cells and the suppressive activity on antigen‐driven activation of CD4 + and CD8 + T cells. 271 Moreover, HMGB1 also increases MDSC‐mediated IL‐10 production, enhancing crosstalk between MDSCs and macrophages, and down‐regulating L‐selection on T cells to perturb their location to lymph nodes.…”

Section: Pyroptosis and Tumor Immune Microenvironmentmentioning

confidence: 99%

Pyroptosis, metabolism, and tumor immune microenvironment

Gao

et al. 2021

Clinical & Translational Med

178

121

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In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.

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Section: Pyroptosis and Tumor Immune Microenvironmentmentioning

confidence: 99%

Pyroptosis, metabolism, and tumor immune microenvironment

Gao

et al. 2021

Clinical & Translational Med

178

121

View full text Add to dashboard Cite

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“…Based on their origin, tissue localization, and mechanism of immune suppression, MDSCs can be divided into monocytic MDSCs and polymorphonuclear MDSCs. They exhibit immunosuppressive capability by inhibiting other immune cells in a context-dependent manner [9,10]. Besides, NK cells and DCs are thought to participate in potent anti-tumor immune response, but various immunosuppressive factors tend to restrain their abilities and drive them into pro-tumor phenotypes [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Contradictory roles of lipid metabolism in immune response within the tumor microenvironment

Lei

et al. 2021

J Hematol Oncol

117

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Complex interactions between the immune system and tumor cells exist throughout the initiation and development of cancer. Although the immune system eliminates malignantly transformed cells in the early stage, surviving tumor cells evade host immune defense through various methods and even reprogram the anti-tumor immune response to a pro-tumor phenotype to obtain unlimited growth and metastasis. The high proliferation rate of tumor cells increases the demand for local nutrients and oxygen. Poorly organized vessels can barely satisfy this requirement, which results in an acidic, hypoxic, and glucose-deficient tumor microenvironment. As a result, lipids in the tumor microenvironment are activated and utilized as a primary source of energy and critical regulators in both tumor cells and related immune cells. However, the exact role of lipid metabolism reprogramming in tumor immune response remains unclear. A comprehensive understanding of lipid metabolism dysfunction in the tumor microenvironment and its dual effects on the immune response is critical for mapping the detailed landscape of tumor immunology and developing specific treatments for cancer patients. In this review, we have focused on the dysregulation of lipid metabolism in the tumor microenvironment and have discussed its contradictory roles in the tumor immune response. In addition, we have summarized the current therapeutic strategies targeting lipid metabolism in tumor immunotherapy. This review provides a comprehensive summary of lipid metabolism in the tumor immune response.

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“…However, we inferred that HMGBs were inclined to induce overall immunosuppression in the TIME, since we found that they had uniformly positive correlations with the infiltration of Th2 cells and MDSCs in pancancer. Indeed, interactions between HMGB1 and its receptors are critical for the differentiation and activation of MDSCs (Jin et al, 2020) and Tregs (Wild et al, 2012) and the upregulation PD-L1 in the TIME (Wang et al, 2019). Besides, it was evident that HMGB1 could induce a dominance of Th2-type response in inflammation (Ma et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

2021

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Background: High mobility group box (HMGB) proteins are DNA chaperones involved in transcription, DNA repair, and genome stability. Extracellular HMGBs also act as cytokines to promote inflammatory and immune responses. Accumulating evidence has suggested that HMGBs are implicated in cancer pathogenesis; however, their prognostic and immunological values in pan-cancer are not completely clear.Methods: Multiple tools were applied to analyze the expression, genetic alternations, and prognostic and clinicopathological relevance of HMGB in pan-cancer. Correlations between HMGB expression and tumor immune-infiltrating cells (TIICs), immune checkpoint (ICP) expression, microsatellite instability (MSI), and tumor mutational burden (TMB) in pan-cancer were investigated to uncover their interactions with the tumor immune microenvironment (TIME). Gene set enrichment analysis (GSEA) was conducted for correlated genes of HMGBs to expound potential mechanisms.Results: HMGB expression was significantly elevated in various cancers. Both prognostic and clinicopathological significance was observed for HMGB1 in ACC; HMGB2 in ACC, LGG, LIHC, and SKCM; and HMGB3 in ESCA. Prognostic values were also found for HMGB2 in KIRP and MESO and HMGB3 in BRCA, SARC, SKCM, OV, and LAML. The global alternation of HMGBs showed prognostic significance in ACC, KIRC, and UCEC. Furthermore, HMGBs were significantly correlated with TIIC infiltration, ICP expression, MSI, and TMB in various cancers, indicating their regulations on the TIME. Lastly, results of GSEA-illuminated genes positively correlated with HMGBs which were similarly chromosome components participating in DNA activity-associated events.Conclusion: This study demonstrated that HMGBs might be promising predictive biomarkers for the prognosis and immunotherapeutic response, also immunotherapy targets of multiple cancers.

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Roles of HMGB1 in regulating myeloid-derived suppressor cells in the tumor microenvironment

Cited by 36 publications

References 74 publications

Pyroptosis, metabolism, and tumor immune microenvironment

Pyroptosis, metabolism, and tumor immune microenvironment

Contradictory roles of lipid metabolism in immune response within the tumor microenvironment

Roles of HMGBs in Prognosis and Immunotherapy: A Pan-Cancer Analysis

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