Hypoxia enhances IL-10-producing B cell generation through upregulating high-mobility group B1 on tumor cell-released autophagosomes

Zhang, Yue; Pan, Ning; Sheng, Yan; Zhou, Meng; Zhang, Wen; Chen, Yongqiang; Huang, Fang; Wang, Lixin

doi:10.1016/j.imlet.2019.09.005

Cited by 14 publications

(7 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was reported that FOXP1 presented physiological reduction in germinal center B cells, implying that the high activity of FOXP1 leading to infantilization of B cells 55 . HMGB1 could be activated after stimulation of hypoxia or inflammation 56 . BCL11A could exert functions in early stages of B cells 57 58 .…”

Section: Resultsmentioning

confidence: 99%

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

Gao

et al. 2022

Preprint

View full text Add to dashboard Cite

While the changes of tumor immune microenvironment (TME) have critical implications for most tumor progression, works that could reveal the compositions and immunity features of TME are needed. Profiling gastric malignant cells at single-cells resolution has shown the transcriptional heterogeneity is represented at different states of gastric cancer, implying that diverse cell states may exist, including immune cells, and all components in TME make some balances in early gastric cancer (EGC) progression. However, it remains unclear how immune cells contributing malignancy of gastritis, constituting general characteristics of gastric TME. Furthermore, the role of specific interactions among cells in gastric TME remains to be illustrated. Here, we performed spatial transcriptomes and single-cell RNA-seq analysis across 18 gastric samples, identifying 17 celltypes and reconstructing their location information. We found that immune cells represented different degree of dysregulations during the progression from non-atrophic gastritis (NAG), atrophic gastritis (AG) to EGC, including imbalance of cytotoxic and inhibitory effects in T cells, maturation inhibition in B cells and malignant genes up-regulated obviously in myeloid cells. Besides, pathway activities showed that hypoxia, reactive oxygen species and fatty metabolism signaling were activated from AG stage, which may accelerate progression of EGC. Moreover, cellular interactions further identified the roles of hypoxia in gastric TME. Overall, the multi-omics data presented in this study offer a comprehensive view of immune cell types, states changes and locations within the gastric tissues during the progression from NAG, AG to EGC, advancing our understanding of the composition and immunity of different gastric states, offering diagnostic and preventive thoughts for EGC.

show abstract

Section: Resultsmentioning

confidence: 99%

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

Gao

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…118 Since the rapid growth of tumors exceeds their nutrient supply, the core of solid tumors is hypoxic and has an extreme low pH. 119,120 Therefore, most cells in the core of the tumor are necrotic and continuously secrete HMGB1. Steady accumulation of HMGB1 in advanced tumors induces chronic inflammation, and aggravates tumor growth and metastasis.…”

Section: Discussion: Potential Factors Altering the Role Of Hmgb1 In Rtmentioning

confidence: 99%

<p>HMGB1 in Radiotherapy: A Two Headed Signal Regulating Tumor Radiosensitivity and Immunity</p>

Liao¹,

Liu²,

Shao³

et al. 2020

OTT

View full text Add to dashboard Cite

Radiotherapy (RT) is a mainstay of cancer treatment. Recent studies have shown that RT not only directly induces cell death but also has late and sustained immune effects. High mobility group box 1 (HMGB1) is a nuclear protein released during RT, with location-dependent functions. It is essential for normal cellular function but also regulates the proliferation and migration of tumor cells by binding to high-affinity receptors. In this review, we summarize recent evidence on the functions of HMGB1 in RT according to the position, intracellular HMGB1 and extracellular HMGB1. Intracellular HMGB1 induces radiation tolerance in tumor cells by promoting DNA damage repair and autophagy. Extracellular HMGB1 plays a more intricate role in radiation-related immune responses, wherein it not only stimulates the anti-tumor immune response by facilitating the recognition of dying tumor cells but is also involved in maintaining immunosuppression. Factors that potentially affect the role of HMGB1 in RT-induced cytotoxicity have also been discussed in the context of possible therapeutic applications, which helps to develop effective and targeted radio-sensitization therapies.

show abstract

“…A similar study found that hypoxia or starvation exerts an immune evasion effect by upregulating HMGB1 on tumor cell-released autophagosomes. Moreover, hypoxic tumor cell-released autophagosomes from human hepatocellular carcinoma cell line HepG2 induce more IL-10-producing B cells, with suppressive functions on CD4+ and CD8+ T cells [ 134 ]. Regulatory B cells are a significant feature of the glioblastoma microenvironment in both clinical and preclinical model samples.…”

Section: Immune Cell Evasionmentioning

confidence: 99%

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion

Shao

Hua

Feng

et al. 2022

IJMS

View full text Add to dashboard Cite

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies.

show abstract

Hypoxia enhances IL-10-producing B cell generation through upregulating high-mobility group B1 on tumor cell-released autophagosomes

Cited by 14 publications

References 25 publications

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

Comprehensive dissection of immune microenvironment in the progression of early gastric cancer at spatial and single-cell resolution

<p>HMGB1 in Radiotherapy: A Two Headed Signal Regulating Tumor Radiosensitivity and Immunity</p>

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion

Contact Info

Product

Resources

About