Hypoxia Induces Overexpression of CCL28 to Recruit Treg Cells to Enhance Angiogenesis in Lung Adenocarcinoma

Liu, Bingchun; Wei, Chunyan

doi:10.1615/jenvironpatholtoxicoloncol.2020035859

Cited by 21 publications

(11 citation statements)

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“…The interplay between hypoxia and angiogenesis has been widely proved. Hypoxia condition has been found to promote endothelial cells, vessel formation by exosome reassembly [ 37 ], and regulatory T cell employment [ 38 ], and direct causes of angiogenesis by hypoxia was mainly attributed to the upregulated VEGF and reprogramming of cancer cells [ 39 ]. lncRNA was recently discovered as a bridge that connects upstream hypoxia genes and downstream targets to activate angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer

Wang

Liang

Zhang

et al. 2022

Journal of Immunology Research

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Hypoxia and angiogenesis are the leading causes of tumor progression, and their strong correlation has been discovered in many cancers. However, their collective function’s prognostic and biological roles were not reported in gastric cancer. Hence, we aimed to investigate the effects of hypoxia and angiogenesis on gastric cancer via sequencing data. This study used weighted gene coexpression network analysis and random forest regression to build a hypoxia-angiogenesis-related model (HARM) via the TCGA-STAD lncRNA data. It estimated the HARM’s correlation with clinical features and its accuracy for survival prediction. Sequential functional analyses were conducted to investigate its biological role, and we next sought the immune landscape status and immunological function variation by ESTIMATE score calculation and GSVA, respectively. Seven different algorithms were conducted to assess the immunocyte infiltration, and TIDE score and immune checkpoint levels were compared between the high- and low-HARM groups. As a result, we found that HARM predicted patient survival with high accuracy and was correlated with higher stages of gastric cancer. Various cancer-associated pathways and macrophage-related regulations were upregulated in the high-HRAM group. The high-HARM group harbored higher immune levels, and M2 macrophages and cancer-associated fibroblasts were particularly highly unfiltered. Furthermore, globally upregulated immune checkpoints and higher TIDE scores were observed in the high-HARM group. Finally, we filtered eight drugs with lower IC50 in the high-HARM group as potential drugs for the HARM-targeted therapy. We believe this study opens up novel perspectives into the interaction between hypoxia-angiogenesis and immunosuppression and will provide novel insights for gastric cancer immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer

Wang

Liang

Zhang

et al. 2022

Journal of Immunology Research

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“…Various studies indicate that Tregs, rather than CD4+ effector T cells, are recruited and activated in the hypoxia zone of colon cancer ( 40 ), melanoma ( 41 ), and lung cancer ( 42 ) to enhance immunosuppression in TME. Of note, HIF1α is also the key metabolic sensor, and this function is largely contributing to metabolism adaptability under hypoxia conditions.…”

Section: Antitumor Immunity Dysfunction Caused By Metabolic Reprogram...mentioning

confidence: 99%

Improving Cancer Immunotherapy: Exploring and Targeting Metabolism in Hypoxia Microenvironment

Wei

2022

Front. Immunol.

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Although immunotherapy has achieved good results in various cancer types, a large proportion of patients are limited from the benefits. Hypoxia and metabolic reprogramming are the common and critical factors that impact immunotherapy response. Here, we present current research on the metabolism reprogramming induced by hypoxia on antitumor immunity and discuss the recent progression among preclinical and clinical trials exploring the therapeutic effects combining targeting hypoxia and metabolism with immunotherapy. By evaluating the little clinical translation of the combined therapy, we provide insight into “understanding and regulating cellular metabolic plasticity under the current tumor microenvironment (TME),” which is essential to explore the strategy for boosting immune responses by targeting the metabolism of tumor cells leading to harsh TMEs. Therefore, we highlight the potential value of advanced single-cell technology in revealing the metabolic heterogeneity and corresponding phenotype of each cell subtype in the current hypoxic lesion from the clinical patients, which can uncover potential metabolic targets and therapeutic windows to enhance immunotherapy.

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“…Another possible mechanism relies on the expression of transcription factors such as hypoxia-inducible factor (HIF)-1 α . Under hypoxic conditions, upregulation of HIF-1 α promoted the expression of CCL28 in some cancer cells, including lung cancer and HCC (Refs 52, 53). In addition to HIF-1 α , β -catenin signalling also induces transcription of CCL28 in gastric cancer cells, leading to tumour progression through the recruitment of Treg cells (Ref.…”

Section: Introductionmentioning

confidence: 99%

Roles of CCR10/CCL27–CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives

Terefe

Opulencia

Rakhshani

et al. 2022

Expert Rev. Mol. Med.

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Cancer is now one of the major causes of death across the globe. The imbalance of cytokine and chemokine secretion has been reported to be involved in cancer development. Meanwhile, CC chemokines have received considerable interest in cancer research. CCR10, as the latest identified CC chemokine receptor (CCR), has been implicated in the recruitment and infiltration of immune cells, especially lymphocytes, into epithelia such as skin via ligation to two ligands, CCL27 and CCL28. Other than homoeostatic function, several mechanisms have been shown to dysregulate CCR10/CCL27–CCL28 expression in the tumour microenvironment. As such, these receptors and ligands mediate T-cell trafficking in the tumour microenvironment. Depending on the types of lymphocytes recruited, CCR10/CCL27–CCL28 interaction has been shown to play conflicting roles in cancer development. If they were T helper and cytotoxic T cells and natural killer cells, the role of this axis would be tumour-suppressive. In contrast, if CCR10/CCL27–CCL28 recruited regulatory T cells, cancer-associated fibroblasts or myeloid-derived suppressor cells, it would lead to tumour progression. In addition to the trafficking of lymphocytes and immune cells, CCR10 also leads to the migration of tumour cells or endothelial cells (called angiogenesis and lymphangiogenesis) to promote tumour metastasis. Furthermore, CCR10 signalling triggers tumour-promoting signalling such as PI3K/AKT and mitogen-activated protein kinase/extracellular signal-regulated kinase, resulting in tumour cell growth. Since CCR10/CCL27–CCL28 is dysregulated in the tumour tissues, it is suggested that analysis and measurement of them might predict tumour development. Finally, it is hoped using therapeutic approaches based on this axis might increase our knowledge to overcome tumour progression.

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Hypoxia Induces Overexpression of CCL28 to Recruit Treg Cells to Enhance Angiogenesis in Lung Adenocarcinoma

Cited by 21 publications

References 0 publications

Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer

Identification of a Hypoxia-Angiogenesis lncRNA Signature Participating in Immunosuppression in Gastric Cancer

Improving Cancer Immunotherapy: Exploring and Targeting Metabolism in Hypoxia Microenvironment

Roles of CCR10/CCL27–CCL28 axis in tumour development: mechanisms, diagnostic and therapeutic approaches, and perspectives

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