scholarly journals Influence of lymphocytes T and myeloid-derived suppressor cells on inhibition of antitumor response

2016 ◽  
Vol 72 (12) ◽  
pp. 735-739
Author(s):  
Joanna Mucha ◽  
Tomasz Motyl ◽  
Magdalena Król
Keyword(s):  
Cancer Cells ◽  
Tumour Progression ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Main Task ◽  
Myeloid Derived Suppressor Cells ◽  
Inflammatory Infiltration ◽  
Myeloid Suppressor Cells ◽  
Special Groups ◽  
Anti Tumour Effect

For many years research on tumour development focused exclusively on the functions of cancer cells. Less attention was paid to tumour-associated cells, which form the tumour microenvironment. Nowadays we know that inflammatory infiltration cells associated with tumour proliferation may have a pro-tumour or an anti-tumour effect. Current studies are focused on interaction (cross-talk) between cells in the tumour microenvironment. Myeloid suppressor cells (MDSCs) and lymphocytes T are special groups of cells associated with tumour. Interaction between cancer cells, MDSCs and lymphocytes T leads to the development of an immunosuppression network that prevents effective combat against cancer cells and creates conditions favourable for tumour progression, migration and metastasis. The understanding of the crosstalk between cancer cells and immune cells has become the main task of scientists and oncologists.

scholarly journals A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2700
Author(s):  
Francesca Hofer ◽  
Gianna Di Sario ◽  
Chiara Musiu ◽  
Silvia Sartoris ◽  
Francesco De Sanctis ◽  
...  
Keyword(s):  
Metabolic Network ◽  
Cancer Progression ◽  
Immune Cells ◽  
Energy Demand ◽  
Tumour Progression ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Reprogramming ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Proliferation And Differentiation

Myeloid-derived suppressor cells (MDSCs) constitute a plastic and heterogeneous cell population among immune cells within the tumour microenvironment (TME) that support cancer progression and resistance to therapy. During tumour progression, cancer cells modify their metabolism to sustain an increased energy demand to cope with uncontrolled cell proliferation and differentiation. This metabolic reprogramming of cancer establishes competition for nutrients between tumour cells and leukocytes and most importantly, among tumour-infiltrating immune cells. Thus, MDSCs that have emerged as one of the most decisive immune regulators of TME exhibit an increase in glycolysis and fatty acid metabolism and also an upregulation of enzymes that catabolise essential metabolites. This complex metabolic network is not only crucial for MDSC survival and accumulation in the TME but also for enhancing immunosuppressive functions toward immune effectors. In this review, we discuss recent progress in the field of MDSC-associated metabolic pathways that could facilitate therapeutic targeting of these cells during cancer progression.

scholarly journals Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 561 ◽  
Author(s):  
Andrew M. K. Law ◽  
Fatima Valdes-Mora ◽  
David Gallego-Ortega
Keyword(s):  
Cancer Progression ◽  
Therapeutic Target ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Myeloid Derived Suppressor Cells ◽  
Cancer Treatments ◽  
Patient Response

The emergence of immunotherapy has been an astounding breakthrough in cancer treatments. In particular, immune checkpoint inhibitors, targeting PD-1 and CTLA-4, have shown remarkable therapeutic outcomes. However, response rates from immunotherapy have been reported to be varied, with some having pronounced success and others with minimal to no clinical benefit. An important aspect associated with this discrepancy in patient response is the immune-suppressive effects elicited by the tumour microenvironment (TME). Immune suppression plays a pivotal role in regulating cancer progression, metastasis, and reducing immunotherapy success. Most notably, myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells, have potent mechanisms to inhibit T-cell and NK-cell activity to promote tumour growth, development of the pre-metastatic niche, and contribute to resistance to immunotherapy. Accumulating research indicates that MDSC can be a therapeutic target to alleviate their pro-tumourigenic functions and immunosuppressive activities to bolster the efficacy of checkpoint inhibitors. In this review, we provide an overview of the general immunotherapeutic approaches and discuss the characterisation, expansion, and activities of MDSCs with the current treatments used to target them either as a single therapeutic target or synergistically in combination with immunotherapy.

scholarly journals Sustained Inflammatory Signalling through Stat1/Stat2/IRF9 Is Associated with Amoeboid Phenotype of Melanoma Cells

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2450
Author(s):  
Aneta Gandalovičová ◽  
Anna-Marie Šůchová ◽  
Vladimír Čermák ◽  
Ladislav Merta ◽  
Daniel Rösel ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Type I Interferon ◽  
Tumour Progression ◽  
Tumour Microenvironment ◽  
Melanoma Cells ◽  
Interferon Response ◽  
Type I ◽  
Expression Of Genes ◽  
Interferon Signalling ◽  
Inflammatory Signalling

The invasive behaviour of cancer cells underlies metastatic dissemination; however, due to the large plasticity of invasion modes, it is challenging to target. It is now widely accepted that various secreted cytokines modulate the tumour microenvironment and pro-inflammatory signalling can promote tumour progression. Here, we report that cells after mesenchymal–amoeboid transition show the increased expression of genes associated with the type I interferon response. Moreover, the sustained activation of type I interferon signalling in response to IFNβ mediated by the Stat1/Stat2/IRF9 complex enhances the round amoeboid phenotype in melanoma cells, whereas its downregulation by various approaches promotes the mesenchymal invasive phenotype. Overall, we demonstrate that interferon signalling is associated with the amoeboid phenotype of cancer cells and suggest a novel role of IFNβ in promoting cancer invasion plasticity, aside from its known role as a tumour suppressor.

scholarly journals Energy metabolism manipulates the fate and function of tumour myeloid-derived suppressor cells

2019 ◽  
Vol 122 (1) ◽  
pp. 23-29 ◽  
Author(s):  
Cong Hu ◽  
Bo Pang ◽  
Guangzhu Lin ◽  
Yu Zhen ◽  
Huanfa Yi
Keyword(s):  
Metabolic Pathways ◽  
Immune Surveillance ◽  
Suppressor Cells ◽  
Tumour Microenvironment ◽  
Metabolic Energy ◽  
Myeloid Derived Suppressor Cells ◽  
Cell Responses ◽  
And Function ◽  
Promote Tumour Development

AbstractIn recent years, a large number of studies have been carried out in the field of immune metabolism, highlighting the role of metabolic energy reprogramming in altering the function of immune cells. Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells generated during a large array of pathological conditions, such as cancer, inflammation, and infection, and show remarkable ability to suppress T-cell responses. These cells can also change their metabolic pathways in response to various pathogen-derived or inflammatory signals. In this review, we focus on the roles of glucose, fatty acid (FA), and amino acid (AA) metabolism in the differentiation and function of MDSCs in the tumour microenvironment, highlighting their potential as targets to inhibit tumour growth and enhance tumour immune surveillance by the host. We further highlight the remaining gaps in knowledge concerning the mechanisms determining the plasticity of MDSCs in different environments and their specific responses in the tumour environment. Therefore, this review should motivate further research in the field of metabolomics to identify the metabolic pathways driving the enhancement of MDSCs in order to effectively target their ability to promote tumour development and progression.

scholarly journals ApoE-TREM2 axis induces pathogenic senescent-like myeloid cells in prostate cancer

2021 ◽  
Author(s):  
Arianna Calcinotto ◽  
Nicolò Bancaro ◽  
Martina Troiani ◽  
Rydell Arzola ◽  
Angela Rita Elia ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Histone Deacetylase Inhibitors ◽  
Tumour Progression ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Treatment Resistance ◽  
Tumour Microenvironment ◽  
Tumour Cells ◽  
Mrna Levels ◽  
Immature Myeloid Cells

Abstract Tumour cells promote the expansion and intra-tumoural recruitment of Myeloid-derived suppressor cells (MDSCs), a subset of immature myeloid cells, that support tumour cell proliferation and confer treatment resistance. While immature myeloid cells have a very short lifespan, whether pathogenic MDSCs can persist in the tumour microenvironment remains unknown. Here, we report the identification of a subset of long-lasting MDSCs that upregulate markers of cellular senescence and the TREM2 receptor. Senescent-like MDSCs possess higher pro-inflammatory capabilities compared to canonical MDSCs. Genetic and pharmacological elimination of senescent-like MDSCs decreases tumour progression in different mouse models of prostate cancer. Mechanistically, we find that Apolipoprotein E (ApoE) secreted by prostate tumour cells binds TREM2 in senescent-like MDSCs, thereby regulating the survival of these cells. ApoE and TREM2 mRNA levels are upregulated in prostate cancers and correlate with poor patients’ prognosis. Taken together, these results reveal a novel mechanism by which the tumour microenvironment shapes the intra-tumoural immune response. Pathogenic senescent-like MDSCs persist longer in the tumour microenvironment and can be eliminated by histone deacetylase inhibitors enhancing the efficacy of standard therapy in prostate cancer.

scholarly journals Mesenchymal Transition and Dissemination of Cancer Cells Is Driven by Myeloid-Derived Suppressor Cells Infiltrating the Primary Tumor

PLoS Biology ◽  
2011 ◽  
Vol 9 (9) ◽  
pp. e1001162 ◽  
Author(s):  
Benjamin Toh ◽  
Xiaojie Wang ◽  
Jo Keeble ◽  
Wen Jing Sim ◽  
Karen Khoo ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Primary Tumor ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Mesenchymal Transition

scholarly journals Doxorubicin resistant cancer cells activate myeloid-derived suppressor cells by releasing PGE2

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuan Rong ◽  
Chun-Hui Yuan ◽  
Zhen Qu ◽  
Hu Zhou ◽  
Qing Guan ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells

scholarly journals Functional and Molecular Characterization of Myeloid Suppressor Cells Expanded During Lymphoma Tumour Progression

2008 ◽  
Vol 59 (6) ◽  
pp. 635-635
Author(s):  
S. Meerschaut ◽  
Y. Liu ◽  
G. H. G. Hassanzadeh ◽  
G. Raes ◽  
P. De Baetselier ◽  
...  
Keyword(s):  
Molecular Characterization ◽  
Tumour Progression ◽  
Suppressor Cells ◽  
Myeloid Suppressor Cells
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