Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Myeloid-Derived Suppressor Cells in Solid Tumors.

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are one of the main suppressive cell population of the immune system. They play a pivotal role in the establishment of the tumor microenvironment (TME). In the context of cancers or other pathological conditions, MDSCs can differentiate, expand, and migrate in large quantities during circulation, inhibiting the cytotoxic functions of T cells and NK cells. This process is regulated by ROS, iNOS/NO, arginase-1, and multiple soluble cytokines. The definition of MDSCs and their phenotypes in humans are not as well represented as in other organisms such as mice, owing to the absence of the cognate molecule. However, a comprehensive understanding of the differences between different species and subsets will be beneficial for clarifying the immunosuppressive properties and potential clinical values of these cells during tumor progression. Recently, experimental evidence and clinical investigations have demonstrated that MDSCs have a close relationship with poor prognosis and drug resistance, which is considered to be a leading marker for practical applications and therapeutic methods. In this review, we summarize the remarkable position of MDSCs in solid tumors, explain their classifications in different models, and introduce new treatment approaches to target MDSCs to better understand the advancement of new approaches to cancer treatment.

SUBMITTER: Ma T

PROVIDER: S-EPMC8774531 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Myeloid-derived Suppressor Cells in Colorectal Cancer

Project description:The aim of the study is to evaluate whether the preoperative level of myeloid-derived suppressor cells is associated with postoperative complications classified by Clavien-Dindo categories. Levels of all MDSC, polymorphonuclear MDSC (PMNMDSC), monocytic MDSC (MMDSC), early-stage MDSC (EMDSC) and monocytic to polymorphonuclear MDSC ratio (M/PMN MDCS) were established and compared in patients with postoperative complications, severe postoperative complications (>= IIIA according to Clavien-Dindo) and severe septic complications.

| 2381881 | ecrin-mdr-crc

The Role of Myeloid-Derived Suppressor Cells in Patients with Solid Tumors: A Meta-Analysis.

Project description:Targeting immune cells or factors are effective for patients with solid tumors. Myeloid-derived suppressor cells (MDSCs) are known to have immunosuppressive functions, and the levels of MDSCs in patients with solid tumor are assumed to have prognostic values. This meta-analysis aimed at evaluating the relationship between MDSCs and the prognosis of patients with solid tumors. We searched articles in PUBMED and EMBASE comprehensively, updated to March 2016. Eight studies with 442 patients were included in the meta-analysis. We analyzed pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). The results showed that MDSCs were associated with poor OS (HR, 1.94; 95% confidence interval [CI], 1.42-2.66; P < 0.0001) in patients with solid tumors. PFS/RFS (HR, 1.85; 95% CI, 1.16-2.97; P = 0.01) also indicated the association between MDSCs and prognosis. The HRs and 95% CIs for OS in Asian and non-Asian patients were 2.53 (95% CI 1.61-3.42, p < 0.00001) and 1.67 (95% CI 1.14-2.46, p < 0.0001), respectively. We further analyzed the data according to tumor types. The combined HRs and 95% CIs for OS were 1.26 (95% CI 1.10-1.44, p = 0.0003) for gastrointestinal (GI) cancer, 2.59 (95% CI 1.69-3.98, p < 0.0001) for hepatocellular carcinoma (HCC) and 1.86 (95% CI 1.26-2.75, p = 0.002) for other tumor types. In conclusion, MDSCs had a fine prognostic value for OS and PFS/RFS in patients with solid tumors. MDSCs could be used as biomarkers to evaluate prognosis in clinical practice.

| S-EPMC5079654 | biostudies-literature

Cross-talk among myeloid-derived suppressor cells, macrophages, and tumor cells impacts the inflammatory milieu of solid tumors.

Project description:MDSC and macrophages are present in most solid tumors and are important drivers of immune suppression and inflammation. It is established that cross-talk between MDSC and macrophages impacts anti-tumor immunity; however, interactions between tumor cells and MDSC or macrophages are less well studied. To examine potential interactions between these cells, we studied the impact of MDSC, macrophages, and four murine tumor cell lines on each other, both in vitro and in vivo. We focused on IL-6, IL-10, IL-12, TNF-α, and NO, as these molecules are produced by macrophages, MDSC, and many tumor cells; are present in most solid tumors; and regulate inflammation. In vitro studies demonstrated that MDSC-produced IL-10 decreased macrophage IL-6 and TNF-α and increased NO. IL-6 indirectly regulated MDSC IL-10. Tumor cells increased MDSC IL-6 and vice versa. Tumor cells also increased macrophage IL-6 and NO and decreased macrophage TNF-α. Tumor cell-driven macrophage IL-6 was reduced by MDSC, and tumor cells and MDSC enhanced macrophage NO. In vivo analysis of solid tumors identified IL-6 and IL-10 as the dominant cytokines and demonstrated that these molecules were produced predominantly by stromal cells. These results suggest that inflammation within solid tumors is regulated by the ratio of tumor cells to MDSC and macrophages and that interactions of these cells have the potential to alter significantly the inflammatory milieu within the tumor microenvironment.

| S-EPMC4226789 | biostudies-literature

mTOR masters monocytic myeloid-derived suppressor cells in mice with allografts or tumors.

Project description:CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) play critical roles in controlling the processes of tumors, infections, autoimmunity and graft rejection. Immunosuppressive drug rapamycin (RPM), targeting on the key cellular metabolism molecule mTOR, is currently used in clinics to treat patients with allo-grafts, autoimmune diseases and tumors. However, the effect of RPM on MDSCs has not been studied. RPM significantly decreases the cell number and the immunosuppressive ability on T cells of CD11b(+) Ly6C(high) monocytic MDSCs (M-MDSCs) in both allo-grafts-transplanted and tumor-bearing mice respectively. Mice with a myeloid-specific deletion of mTOR have poor M-MDSCs after grafting with allo-skin tissue or a tumor. Grafting of allo-skin or tumors significantly activates glycolysis pathways in myeloid precursor cells in bone marrow, which is inhibited by RPM or mTOR deletion. 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway, inhibits M-MDSC differentiation from precursors, while enhancing glycolysis by metformin significantly rescues the RPM-caused deficiency of M-MDSCs. Therefore, we offer evidence supporting that mTOR is an intrinsic factor essential for the differentiation and immunosuppressive function of M-MDSCs and that these metabolism-relevant medicines may impact MDSCs-mediated immunosuppression or immune tolerance induction, which is of considerable clinical importance in treating graft rejection, autoimmune diseases and cancers.

| S-EPMC4735296 | biostudies-literature

Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation.

Project description:Among the various immunological and non-immunological tumor-promoting activities of myeloid-derived suppressor cells (MDSCs), their immunosuppressive capacity remains a key hallmark. Effort in the past decade has provided us with a clearer view of the suppressive nature of MDSCs. More suppressive pathways have been identified, and their recognized targets have been expanded from T cells and natural killer (NK) cells to other immune cells. These novel mechanisms and targets afford MDSCs versatility in suppressing both innate and adaptive immunity. On the other hand, a better understanding of the regulation of their development and function has been unveiled. This intricate regulatory network, consisting of tumor cells, stromal cells, soluble mediators, and hostile physical conditions, reveals bi-directional crosstalk between MDSCs and the tumor microenvironment. In this article, we will review available information on how MDSCs exert their immunosuppressive function and how they are regulated in the tumor milieu. As MDSCs are a well-established obstacle to anti-tumor immunity, new insights in the potential synergistic combination of MDSC-targeted therapy and immunotherapy will be discussed.

| S-EPMC7387650 | biostudies-literature

Myeloid-derived suppressor cells in gliomas.

Project description:Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors and precursors at different stages of differentiation into granulocytes, macrophages, and dendritic cells. Blockade of their differentiation into mature myeloid cells in cancer results in an expansion of this population. High-grade gliomas are the most common malignant tumours of the central nervous system (CNS), with a poor prognosis despite intensive radiation and chemotherapy. Histopathological and flow cytometry analyses of human and rodent experimental gliomas revealed the extensive heterogeneity of immune cells infiltrating gliomas and their microenvironment. Immune cell infiltrates consist of: resident (microglia) and peripheral macrophages, granulocytes, myeloid-derived suppressor cells, and T lymphocytes. Intratumoural density of glioma-associated MDSCs correlates positively with the histological grade of gliomas and patient's survival. MDSCs have the ability to attract T regulatory lymphocytes to the tumour, but block the activation of tumour-reactive CD4+ T helper cells and cytotoxic CD8+ T cells. Immunomodulatory mechanisms employed by malignant gliomas pose an appalling challenge to brain tumour immunotherapy. In this mini-review we describe phenotypic and functional characteristics of MDSCs in humans and rodents, and their occurrence and potential roles in glioma progression. While understanding the complexity of immune cell interactions in the glioma microenvironment is far from being accomplished, there is significant progress that may lead to the development of immunotherapy for gliomas.

| S-EPMC5371700 | biostudies-literature

Myeloid-Derived Suppressor Cells in Colorectal Cancer.

Project description:Colorectal cancer (CRC) remains one of the most common malignancies diagnosed worldwide. The pathogenesis of CRC is complex and involves, among others, accumulation of genetic predispositions and epigenetic factors, dietary habits, alterations in gut microbiota, and lack of physical activity. A growing body of evidence suggests that immune cells play different roles in CRC, comprising both pro- and anti-tumorigenic functions. Immunosuppression observed during cancer development and progression is a result of the orchestration of many cell types, including myeloid-derived suppressor cells (MDSCs). MDSCs, along with other cells, stimulate tumor growth, angiogenesis, and formation of metastases. This article focuses on MDSCs in relation to their role in the initiation and progression of CRC. Possible forms of immunotherapies targeting MDSCs in CRC are also discussed.

| S-EPMC7426395 | biostudies-literature

Myeloid derived suppressor cells: Targets for therapy.

Project description:The goal of achieving measurable response with cancer immunotherapy requires counteracting the immunosuppressive characteristics of tumors. One of the mechanisms that tumors utilize to escape immunosurveillance is the activation of myeloid derived suppressor cells (MDSCs). Upon activation by tumor-derived signals, MDSCs inhibit the ability of the host to mount an anti-tumor immune response via their capacity to suppress both the innate and adaptive immune systems. Despite their relatively recent discovery and characterization, anti-MDSC agents have been identified, which may improve immunotherapy efficacy.

| S-EPMC3654606 | biostudies-literature

Myeloid-Derived Suppressor Cells in Lung Transplantation.

Project description:Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage. MDSCs expand in pathological situations, such as chronic infection, cancer, autoimmunity, and allograft rejection. As chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx), MDSCs may play a role in its pathophysiology. We assessed phenotype and frequency of MDSCs in peripheral blood from lung transplant recipients and its relationship to post-transplant complications and immunosuppression. Granulocytic (G)-MDSC were identified and quantified by flow cytometry of blood from 4 control subjects and 20 lung transplant patients (stable n = 6, infection n = 5; CLAD n = 9). G-MDSC functionality was assessed in vitro by their capability to block CD4 and CD8 T cell proliferation. More G-MDSC could be assessed using EDTA tubes compared to heparin tubes (p = 0.004). G-MDSC were increased in stable lung transplant recipients vs. non-transplant controls (52.1% vs. 9.4%; p = 0.0095). The infection or CLAD groups had lower G-MDSCs vs. stable recipients (28.2%p = 0.041 and 33.0%; p = 0.088, respectively), but were not different among CLAD phenotypes. G-MDSC tended to correlate with cyclosporine A and tacrolimus levels (r 2 = 0.18; r 2 = 0.17). CD4 and CD8 cells proliferation decreased by 50 and 80% if co-cultured with MDSCs (1:6 and 1:2 MDSC:T-cell ratio, respectively). In conclusion, circulating MDSCs are measurable, functional and have a G-MDSC phenotype in lung transplant patients. Their frequency is increased in stable patients, decreased during post-transplant complications, and related to level of immunosuppression. This study may pave the way for further investigations of MDSC in the context of lung transplantation.

| S-EPMC6497753 | biostudies-literature

CD115<sup>-</sup> monocytic myeloid-derived suppressor cells are precursors of OLFM4<sup>high</sup> polymorphonuclear myeloid-derived suppressor cells.

Project description:Myeloid-derived suppressor cells (MDSCs) consist of monocytic (M-) MDSCs and polymorphonuclear (PMN-) MDSCs that contribute to an immunosuppressive environment in tumor-bearing hosts. However, research on the phenotypic and functional heterogeneity of MDSCs in tumor-bearing hosts and across different disease stage is limited. Here we subdivide M-MDSCs based on CD115 expression and report that CD115- M-MDSCs are functionally distinct from CD115+ M-MDSCs. CD115- M-MDSCs increased in bone marrow and blood as tumors progressed. Transcriptome analysis revealed that CD115- M-MDSCs expressed higher levels of neutrophil-related genes. Moreover, isolated CD115- M-MDSCs had higher potential to be differentiated into PMN-MDSCs compared with CD115+ M-MDSCs. Of note, CD115- M-MDSCs were able to differentiate into both olfactomedin 4 (OLFM4)hi and OLFM4lo PMN-MDSCs, whereas CD115+ M-MDSCs differentiated into a smaller proportion of OLFM4lo PMN-MDSCs. In vivo, M-MDSC to PMN-MDSC differentiation occurred most frequently in bone marrow while M-MDSCs preferentially differentiated into tumor-associated macrophages in the tumor mass. Our study reveals the presence of previously unrecognized subtypes of CD115- M-MDSCs in tumor-bearing hosts and demonstrates their cellular plasticity during tumorigenesis.

| S-EPMC10017706 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data