Human T cells modulate myeloid-derived suppressor cells through a TNF-α-mediated mechanism

Bauswein, Markus; Singh, Anurag; Ralhan, Anjali; Neri, Davide; Fuchs, Katharina; Blanz, Kelly Daryll; Schäfer, Iris; Hector, Andreas; Handgretinger, Rupert; Hartl, Dominik; Rieber, Nikolaus

doi:10.1016/j.imlet.2018.07.010

Cited by 9 publications

(8 citation statements)

References 30 publications

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“…Thus we suggest that M-MDSC in the group of T1D subjects engage a different mechanism to suppress T cells, preferentially TGF-β production and cell-cell contact between M-MDSC and T cells. It is also worth mentioning that TNF-α, elevated in T1D patients [67], was described to augment the M-MDSC suppressive activity accompanied by T cell CD3z chain downregulation [66,83]. Moreover, MDSC independent effect of lowering CD3z chain should be also taken into account.…”

Section: Plos Onementioning

confidence: 99%

Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

et al. 2020

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Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of immature myeloid cells with immunoregulatory function in cancer and autoimmune diseases. In humans, two subsets of MDSC were determined based on the characteristic surface markers, monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC). Expansion of MDSC has been reported in some murine models and patients with autoimmune diseases and their immune-suppressive properties were characterized. However, the exact role of MDSC in the pathogenesis of autoimmune diseases is more complex and/or controversial. In type 1 diabetes mellitus (T1D), the increased frequency of MDSC was found in the blood of T1D patients but their suppressor capacity was diminished. In our study, we assessed the role of M-MDSC in the pathogenesis of T1D and showed for the first time the increased frequency of M-MDSC not only in the blood of T1D patients but also in their at-risk relatives compared to healthy donors. T1D patients with inadequate long term metabolic control showed an elevation of M-MDSC compared to patients with better disease control. Furthermore, we described the positive correlation between the percentage of M-MDSC and Th17 cells and IFN-γ producing T cells in T1D patients and their at-risk relatives. Finally, we found that the ability of M-MDSC to suppress autologous T cells is efficient only at the high MDSC: T cells ratio and dependent on cell-cell-contact and TGF-β production. Our data show that the engagement of MDSC in the pathogenesis of T1D is evident, yet not entirely explored and more experiments are required to clarify whether MDSC are beneficial or harmful in T1D.

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Section: Plos Onementioning

confidence: 99%

Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

et al. 2020

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“…Human T cells are of pivotal importance in inducing a population of PMN-MDSCs. Through a direct cell-cell mechanism with the use of the transmembrane form of TNF-α (tmTNF-α) activation, CD4 + T cells promote the development of a PMN-MDSC population using CD33 + myeloid cell reserves, while the CD3 + subpopulation shows a correlation with anti-apoptotic activity toward PM-MDSCs [79]. Cancer cells release CXCL1 and CXCL2 chemokines, which in turn induce the generation of mo-MDSCs as a bone marrow cell subpopulation [80].…”

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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“…Increased IL-2 levels extend MDSC lifespan in a dose-relevant manner, starting a backfire and impeding better therapeutic efficacy. Besides, augmented activated T cells and their increased GM-CSF production amplify the effect (Bauswein et al, 2018). Another study reported that IL-2 administration prevented the apoptosis of MDSCs and prolonged their survival, augmenting the destructive capability this cluster of cells (Pericle et al, 1994).…”

Section: Effect On Modulatory Cytokinesmentioning

confidence: 98%

Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy

Shi

et al. 2021

Front. Cell Dev. Biol.

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T lymphocytes function as major players in antigen-mediated cytotoxicity and have become powerful tools for exploiting the immune system in tumor elimination. Several types of T cell-based immunotherapies have been prescribed to cancer patients with durable immunological response. Such strategies include immune checkpoint inhibitors, adoptive T cell therapy, cancer vaccines, oncolytic virus, and modulatory cytokines. However, the majority of cancer patients still failed to take the advantage of these kinds of treatments. Currently, extensive attempts are being made to uncover the potential mechanism of immunotherapy resistance, and myeloid-derived suppressor cells (MDSCs) have been identified as one of vital interpretable factors. Here, we discuss the immunosuppressive mechanism of MDSCs and their contributions to failures of T cell-based immunotherapy. Additionally, we summarize combination therapies to ameliorate the efficacy of T cell-based immunotherapy.

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Human T cells modulate myeloid-derived suppressor cells through a TNF-α-mediated mechanism

Cited by 9 publications

References 30 publications

Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

Myeloid - derived suppressor cells in Type 1 diabetes are an expanded population exhibiting diverse T-cell suppressor mechanisms

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

Myeloid-Derived Suppressor Cells: Implications in the Resistance of Malignant Tumors to T Cell-Based Immunotherapy

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