CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer

Mao, Fang‐Yuan; Zhao, Yongliang; Lv, Yi-pin; Teng, Yong‐Sheng; Kong, Hui; Liu, Yugang; Wu, Xiaolong; Hao, Chuan-jie; Chen, Weisan; Duan, Mubing; Han, Bin; Ma, Qiang; Wang, Tingting; Li, Peng; Zhang, Jinyu; Cheng, Ping; Su, Chen; Fu, Xiaolong; Zou, Quanming; Guo, Gang; Guo, Xiaolan; Zhuang, Yuan

doi:10.1038/s41419-018-0803-7

Cited by 42 publications

(39 citation statements)

References 33 publications

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“…Activation of this pathway suppresses CD8 + T cells and positively correlates with disease progression and patient survival rates in general. Increased levels of IL-6 and IL-8 in patients with GC have been found to positively correlate with Arg1 and MDSCs [89]. There are reports stating that Arg1 is not consecutively released by MDSCs and that its synthesis depends on the activity of certain interleukins, i.e., IL-6, IL-4, GM-CSF and IL-10 are known to regulate the secretion of Arg1 by MDSCs.…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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“…Since then, many other studies confirmed that immature tumor myeloid cells express ARG1 in mice and humans with cancer and that the activity of this enzyme is involved in suppression of T-cell response (132,(143)(144)(145)(146). The majority of studies indicate that arginase plays a more important role in PMN-MDSC rather than M-MDSC (103,(147)(148)(149). However, the role of this enzyme in the regulatory activities of the latter cells should not be completely dismissed.…”

Section: Arginase In Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

Myeloid Cell-Derived Arginase in Cancer Immune Response

et al. 2020

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Amino acid metabolism is a critical regulator of the immune response, and its modulating becomes a promising approach in various forms of immunotherapy. Insufficient concentrations of essential amino acids restrict T-cells activation and proliferation. However, only arginases, that degrade L-arginine, as well as enzymes that hydrolyze L-tryptophan are substantially increased in cancer. Two arginase isoforms, ARG1 and ARG2, have been found to be present in tumors and their increased activity usually correlates with more advanced disease and worse clinical prognosis. Nearly all types of myeloid cells were reported to produce arginases and the increased numbers of various populations of myeloid-derived suppressor cells and macrophages correlate with inferior clinical outcomes of cancer patients. Here, we describe the role of arginases produced by myeloid cells in regulating various populations of immune cells, discuss molecular mechanisms of immunoregulatory processes involving L-arginine metabolism and outline therapeutic approaches to mitigate the negative effects of arginases on antitumor immune response. Development of potent arginase inhibitors, with improved pharmacokinetic properties, may lead to the elaboration of novel therapeutic strategies based on targeting immunoregulatory pathways controlled by L-arginine degradation.

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“…Previous studies have reported that myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells (IMCs) infiltrating the tumor microenvironment with potent tumor-associated T lymphocyte tolerance and immunosuppressive activity [4,6,7]. MDSCs are characterized by cell-surface markers CD11b + GR1 + in mice, while they are LIN − HLA-DR − CD33 + or CD11b + CD14 − CD33 + in humans.…”

Section: Backgoundmentioning

confidence: 99%

Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression

Gao

et al. 2020

Cell Commun Signal

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Backgound: Although Myeloid-derived suppressor cells (MDSCs) have a prominent ability to suppress the immune responses of T lymphocytes and propel tumor immune escape, a lack of profound systemic immunesuppression in tumor-bearing mice and tumor patients. The underlying mechanism of these remains unclear. Methods: For this purpose, renal cancer-derived exosomes (RDEs) were first labeled with PKH67 and been observed the internalization by MDSCs. Flow cytometry analysis showed the proportion and activity change of MDSCs in spleen and bone marrow induced by RDEs. Further, western blot experiments were used to verify triggered mechanism of MDSCs by RDEs. Finally, proliferation and cytotoxicity of cytotoxic T lymphocytes (CTLs) cocultured with MDSCs in vitro and a series of experiments in vivo were performed to demonstrate the specific inhibitory effect of RDEs-induced MDSCs. Results: This study suggested that RDEs crucially contributed to presenting antigenic information, activating and driving specific immunosuppressive effect to MDSCs. HSP70, which is highly expressed in RDEs, initiate this process in a toll like receptor 2 (TLR2)-dependent manner. Importantly, RDEs-induced MDSCs could exert an antigen-specific immunosuppression effect on CTL and specific promote renal tumors-growth and immune escape in consequence. Conclusion: The immunosuppression mediated by MDSCs which is induced by RDEs is antigen-specific. HSP70, which is highly expressed in RDEs, plays a pivotal role in this process. Targeted abrogating the function of MDSCs, or eliminating the expression of HSP70 in exosomes, or blocking the crosstalk between them provides a new direction and theoretical support for future immunotherapy.

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CD45+CD33lowCD11bdim myeloid-derived suppressor cells suppress CD8+ T cell activity via the IL-6/IL-8-arginase I axis in human gastric cancer

Cited by 42 publications

References 33 publications

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Myeloid Cell-Derived Arginase in Cancer Immune Response

Renal cancer-derived exosomes induce tumor immune tolerance by MDSCs-mediated antigen-specific immunosuppression

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