scholarly journals Myeloid-Derived Suppressor Cells in Immune Microenvironment Promote Progression of Esophagogastric Junction Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Wang ◽  
Haiyan Sun ◽  
Ningning Zhu ◽  
Xianxian Wu ◽  
Zhilin Sui ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Esophagogastric Junction ◽  
Immune Cell ◽  
Suppressor Cells ◽  
The Cancer Genome Atlas ◽  
Low Grade ◽  
Myeloid Derived Suppressor Cells ◽  
M2 Macrophages ◽  
Esophagogastric Junction Adenocarcinoma

Adenocarcinoma of the esophagogastric junction (AEG) is a fatal disease. Accumulating evidence indicates that, for a comprehensive understanding of AEG, studies should be conducted not only to investigate tumor cells, but also the tumor microenvironment (TME). In this study, we collected AEG patient data from The Cancer Genome Atlas, and used the CIBERSORT algorithm to analyze tumor-infiltrating immune cell profiles. The levels of CD8+ T cells and M0 and M2 macrophages were relatively high in AEG tissues. M2 macrophages were abundant in G3 tumors, and neutrophils were associated with poor prognosis. Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immunosuppressive cells which share a similar origin to neutrophils and macrophages. We further analyzed the levels of MDSCs in AEG patients and healthy donors (HD) using flow cytometry. MDSC levels were elevated at tumor sites, with polymorphonuclear MDSCs (PMN-MDSCs) being the predominant subtype. Circulating MDSCs partly represented cells at the tumor site. We observed that PMN-MDSC levels at tumor sites were positively correlated with advanced staging, low grade, lymph node metastasis, and HER2− status. Immunohistochemistry and immunofluorescence analyses indicated that activation of the STAT3 and NF-κB pathways in MDSCs may be a potential mechanism for cancer progression. Our studies provided a comprehensive perspective involving tumor-infiltrating immune cells, and detailed insights into the proportion of MDSCs in AEG and their clinical significance. Together, these findings may improve our current understanding of cancer progression involving tumor-infiltrating immune cells in the TME.

scholarly journals Myeloid-Derived Suppressor Cells and Therapeutic Strategies in Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Hiroshi Katoh ◽  
Masahiko Watanabe
Keyword(s):  
T Cells ◽  
Cancer Progression ◽  
Immune Cell ◽  
Treatment Strategies ◽  
Suppressor Cells ◽  
Response To Treatment ◽  
Solid Cancer ◽  
Myeloid Derived Suppressor Cells ◽  
Immune Cell Population ◽  
Novel Treatment Strategies

Development of solid cancer depends on escape from host immunosurveillance. Various types of immune cells contribute to tumor-induced immune suppression, including tumor associated macrophages, regulatory T cells, type 2 NKT cells, and myeloid-derived suppressor cells (MDSCs). Growing body of evidences shows that MDSCs play pivotal roles among these immunosuppressive cells in multiple steps of cancer progression. MDSCs are immature myeloid cells that arise from myeloid progenitor cells and comprise a heterogeneous immune cell population. MDSCs are characterized by the ability to suppress both adaptive and innate immunities mainly through direct inhibition of the cytotoxic functions of T cells and NK cells. In clinical settings, the number of circulating MDSCs is associated with clinical stages and response to treatment in several cancers. Moreover, MDSCs are reported to contribute to chemoresistant phenotype. Collectively, targeting MDSCs could potentially provide a rationale for novel treatment strategies in cancer. This review summarizes recent understandings of MDSCs in cancer and discusses promissing clinical approaches in cancer patients.

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 Immuno-Phenotyping of High-Grade Glioma Infiltrating Immune Cells Reveals Grade Specific Differences in Cells of Myeloid Origin

2020 ◽  
Author(s):  
Raksha A. Ganesh ◽  
Jayashree V. Raghavan ◽  
Pranali Sonpatki ◽  
Divya Naik ◽  
Priyanka Arunachalam ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Cell ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
High Grade Glioma ◽  
Low Grade ◽  
High Grade ◽  
High Grade Gliomas ◽  
Cell Phenotypes ◽  
Grade Iii

AbstractGliomas are heavily infiltrated with immune cells of myeloid origin. Past studies have shown that high-grade gliomas have a higher proportion of alternatively activated and suppressive myeloid cells when compared to low-grade gliomas, which correlate with poor prognosis. However, the differences in immune cell phenotypes within high-grade gliomas (between grade III and IV) are relatively less explored, and a correlation of phenotypic characteristics between immune cells in the blood and high grade tumors has not been performed. Additionally, myeloid cells of granulocytic origin present in gliomas remain poorly characterized. Herein, we address these questions through phenotypic characterizations of monocytes and neutrophils present in blood and tumors of individuals with glioblastoma (GBM, grade IV) or grade III gliomas. Our data show that CD163 expressing M2 monocytes are present in greater proportions in GBM tissue when compared to grade III glioma tissue. In addition, we observe that neutrophils are highly heterogeneous among individuals with glioma, and a greater proportion of granulocytic myeloid-derived suppressor cells are present in grade III gliomas when compared to GBM. Finally, we show that the expression levels of CD86 and CD63 showed a high correlation between blood and tumor, and suggest that these may be used as possible markers for prognosis.

scholarly journals The Contribution of the Immune System in Bone Metastasis Pathogenesis

2019 ◽  
Vol 20 (4) ◽  
pp. 999 ◽  
Author(s):  
Lisha Xiang ◽  
Daniele Gilkes
Keyword(s):  
Bone Metastasis ◽  
Immune Cells ◽  
Immune Cell ◽  
Suppressor Cells ◽  
Disseminated Tumor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Bone Microenvironment ◽  
Cell Type ◽  
Cell Metastasis

Bone metastasis is associated with significant morbidity for cancer patients and results in a reduced quality of life. The bone marrow is a fertile soil containing a complex composition of immune cells that may actually provide an immune-privileged niche for disseminated tumor cells to colonize and proliferate. In this unique immune milieu, multiple immune cells including T cells, natural killer cells, macrophages, dendritic cells, myeloid-derived suppressor cells, and neutrophils are involved in the process of bone metastasis. In this review, we will discuss the crosstalk between immune cells in bone microenvironment and their involvement with cancer cell metastasis to the bone. Furthermore, we will highlight the anti-tumoral and pro-tumoral function of each immune cell type that contributes to bone metastasis. We will end with a discussion of current therapeutic strategies aimed at sensitizing immune cells.

scholarly journals Multiomic analysis of the function of SPOCK1 across cancers: an integrated bioinformatics approach

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052096265
Author(s):  
Jie Han ◽  
Yihui Rong ◽  
Xudong Gao
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Cancer Cell Line ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Normal Tissues

Objective To investigate SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1 ( SPOCK1) gene expression across The Cancer Genome Atlas (TCGA) cancers, both in cancer versus normal tissues and in different stages across the cancer types. Methods This integrated bioinformatics study used data from several bioinformatics databases (Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, TCGA, Tumor Immune Estimation Resource [TIMER]) to define the expression pattern of the SPOCK1 gene. A survival analysis was undertaken across the cancers. The search tool for retrieval of interacting genes (STRING) database was used to identify proteins that interacted with SPOCK1. Gene Set Enrichment Analysis was conducted to determine pathway enrichment. The TIMER database was used to explore the correlation between SPOCK1 and immune cell infiltration. Results This multiomic analysis showed that the SPOCK1 gene was expressed differently between normal tissues and tumours in several cancers and that it was involved in cancer progression. The overexpression of the SPOCK1 gene was associated with poor clinical outcomes. Analysis of gene expression and tumour-infiltrating immune cells showed that SPOCK1 correlated with several immune cells across cancers. Conclusions This research showed that SPOCK1 might serve as a new target for several cancer therapies in the future.

scholarly journals Fatty Acid Metabolism in Myeloid-Derived Suppressor Cells and Tumor-Associated Macrophages: Key Factor in Cancer Immune Evasion

Cancers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 250
Author(s):  
Sophiya Siddiqui ◽  
Rainer Glauben
Keyword(s):  
Fatty Acids ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Cell Types ◽  
Eukaryotic Cell ◽  
Metabolic Reprogramming ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Associated Macrophages ◽  
Key Factor

The tumor microenvironment (TME) comprises various cell types, soluble factors, viz, metabolites or cytokines, which together play in promoting tumor metastasis. Tumor infiltrating immune cells play an important role against cancer, and metabolic switching in immune cells has been shown to affect activation, differentiation, and polarization from tumor suppressive into immune suppressive phenotypes. Macrophages represent one of the major immune infiltrates into TME. Blood monocyte-derived macrophages and myeloid derived suppressor cells (MDSCs) infiltrating into the TME potentiate hostile tumor progression by polarizing into immunosuppressive tumor-associated macrophages (TAMs). Recent studies in the field of immunometabolism focus on metabolic reprogramming at the TME in polarizing tumor-associated macrophages (TAMs). Lipid droplets (LD), detected in almost every eukaryotic cell type, represent the major source for intra-cellular fatty acids. Previously, LDs were mainly described as storage sites for fatty acids. However, LDs are now recognized to play an integral role in cellular signaling and consequently in inflammation and metabolism-mediated phenotypical changes in immune cells. In recent years, the role of LD dependent metabolism in macrophage functionality and phenotype has been being investigated. In this review article, we discuss fatty acids stored in LDs, their role in modulating metabolism of tumor-infiltrating immune cells and, therefore, in shaping the cancer progression.

scholarly journals Prognostic significance of S100A8-positive immune cells in relation to other immune cell infiltration in pre-invasive and invasive breast cancers

2020 ◽  
Author(s):  
Ji Won Woo ◽  
Yul Ri Chung ◽  
Milim Kim ◽  
Hye Yeon Choi ◽  
Soomin Ahn ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Immune Cells ◽  
Invasive Carcinoma ◽  
Immune Cell ◽  
Dynamic Change ◽  
Prognostic Significance ◽  
Suppressor Cells ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Impact ◽  
Breast Cancers

Abstract Myeloid-derived suppressor cells (MDSCs) play an important role in tumor progression through both immunologic and non-immunologic mechanisms. This study was conducted to evaluate the expression of S100A8, a well-known MDSC marker, and the significance of its expression in pre-invasive and invasive breast cancers. S100A8 expression in tumor cells (TCs) and immune cells (ICs) was assessed by immunohistochemistry, and its association with clinicopathologic features and infiltration of other IC subsets including CD4+, CD8+, and FOXP3+ tumor-infiltrating lymphocytes (TILs) and PD-L1+ ICs was evaluated. S100A8 expression in TCs and ICs showed a positive correlation in pre-invasive carcinoma and invasive carcinoma. S100A8+ ICs, but not S100A8+ TCs, were significantly higher in number in invasive carcinoma than in pre-invasive carcinoma. Infiltration of S100A8+ ICs was revealed as a poor prognostic indicator in pre-invasive and invasive carcinomas, especially in hormone receptor-positive subgroup. Infiltration of CD4+, CD8+, and FOXP3+ TIL subsets and PD-L1+ ICs was significantly higher in S100A8+ IC (+) group than in S100A8+ IC (−) group. Combined analyses of IC subset infiltration revealed that infiltration of S100A8+ ICs was associated with poor clinical outcome in the PD-L1+ IC (−), CD8+ TIL-low, and FOXP3+ TIL-low subgroups. In conclusion, S100A8+ ICs seem to undergo a dynamic change during breast cancer progression in association with other IC subset infiltration. The prognostic impact of S100A8+ IC infiltration was greater in less immunogenic tumors.

scholarly journals Terminating Cancer by Blocking VISTA as a Novel Immunotherapy: Hasta la vista, baby

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji-Eun Irene Yum ◽  
Young-Kwon Hong
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Cancer Progression ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Checkpoint Molecule

VISTA is an up-and-coming immune checkpoint molecule that can become the target of new cancer immunotherapy treatments. Immune cells in the tumor microenvironment can largely influence the progression of cancer through inhibitory and stimulatory pathways. Indeed, VISTA is expressed on many immune cells, including T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and dendritic cells. VISTA has predominantly been shown to act in an immune-suppressing manner that enables cancer progression. This review will delve into results from preclinical murine studies of anti-VISTA monoclonal antibody treatments, bring together recent studies that detect VISTA expression on immune cells from patient tumors of various cancers, and discuss ongoing clinical trials involving VISTA.

scholarly journals Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis

2021 ◽  
Vol 8 ◽  
Author(s):  
Panpan Liu ◽  
Cong Peng ◽  
Xiang Chen ◽  
Lisha Wu ◽  
Mingzhu Yin ◽  
...  
Keyword(s):  
Immune Cells ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Skin Lesions ◽  
Myeloid Derived Suppressor Cells ◽  
M2 Macrophages ◽  
Extracellular Signal Regulated Kinase ◽  
Mhc Ii ◽  
Extracellular Signal ◽  
Proliferation And Differentiation

Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206+ M2 macrophages, and CD11c+MHC-II+ dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation.

scholarly journals The Role of Myeloid-Derived Suppressor Cells (MDSC) in Cancer Progression

Vaccines ◽  
2016 ◽  
Vol 4 (4) ◽  
pp. 36 ◽  
Author(s):  
Viktor Umansky ◽  
Carolin Blattner ◽  
Christoffer Gebhardt ◽  
Jochen Utikal
Keyword(s):  
Cancer Progression ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells
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