scholarly journals Regulatory Effects of Histone Deacetylase Inhibitors on Myeloid-Derived Suppressor Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Yudan Cui ◽  
Jingshan Cai ◽  
Wenxin Wang ◽  
Shengjun Wang
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Histone Deacetylase ◽  
Gene Transcription ◽  
Histone Deacetylase Inhibitors ◽  
Suppressor Cells ◽  
Antitumor Drugs ◽  
Clinical Settings ◽  
Myeloid Derived Suppressor Cells ◽  
Regulatory Effects

Histone deacetylase inhibitors (HDACIs) are antitumor drugs that are being developed for use in clinical settings. HDACIs enhance histone or nonhistone acetylation and promote gene transcription via epigenetic regulation. Importantly, these drugs have cytotoxic or cytostatic properties and can directly inhibit tumor cells. However, how HDACIs regulate immunocytes in the tumor microenvironment, such as myeloid-derived suppressor cells (MDSCs), has yet to be elucidated. In this review, we summarize the effects of different HDACIs on the immunosuppressive function and expansion of MDSCs based on the findings of relevant studies.

scholarly journals Anti-Tumor Effects of Chinese Medicine Compounds by Regulating Immune Cells in Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Fengqian Chen ◽  
Jingquan Li ◽  
Hui Wang ◽  
Qian Ba
Keyword(s):  
Dendritic Cells ◽  
Chinese Medicine ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Traditional Chinese Medicine ◽  
Tumor Cells ◽  
Immune Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Adaptive Immune Cells

As the main cause of death in the world, cancer is one of the major health threats for humans. In recent years, traditional Chinese medicine has gained great attention in oncology due to the features of multi-targets, multi-pathways, and slight side effects. Moreover, lots of traditional Chinese medicine can exert immunomodulatory effects in vivo. In the tumor microenvironment, tumor cells, immune cells as well as other stromal cells often coexist. With the development of cancer, tumor cells proliferate uncontrollably, metastasize aggressively, and modulate the proportion and status of immune cells to debilitate the antitumor immunity. Reversal of immunosuppressive tumor microenvironment plays an essential role in cancer prevention and therapy. Immunotherapy has become the most promising strategy for cancer therapy. Chinese medicine compounds can stimulate the activation and function of immune cells, such as promoting the maturation of dendritic cells and inducing the differentiation of myeloid-derived suppressor cells to dendritic cells and macrophages. In the present review, we summarize and discuss the effects of Chinese medicine compounds on immune cells in the tumor microenvironment, including innate immune cells (dendritic cells, natural killer cells, macrophages, and myeloid-derived suppressor cells) and adaptive immune cells (CD4+/CD8+ T lymphocytes and regulatory T cells), and the various immunomodulatory roles of Chinese medicine compounds in cancer therapy such as improving tumor-derived inflammation, enhancing the immunity after surgery or chemotherapy, blocking the immune checkpoints, et al., aiming to provide more thoughts for the anti-tumor mechanisms and applications of Chinese medicine compounds in terms of tumor immunity.

scholarly journals The Interaction of Tumor Cells and Myeloid-Derived Suppressor Cells in Chronic Myelogenous Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1636-1636
Author(s):  
Hui Xu ◽  
Zunmin Zhu ◽  
Xiaojian Zhu ◽  
Na Shen ◽  
Shu Zhou ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Cells ◽  
Chronic Myelogenous Leukemia ◽  
Suppressor Cells ◽  
K562 Cells ◽  
Myelogenous Leukemia ◽  
Molecular Response ◽  
Myeloid Derived Suppressor Cells ◽  
Transcript Levels ◽  
Cd34 Cells

Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease characterized by the formation of the BCR-ABL fusion gene. At present, basic studies of the pathogenesis of relapse after stopping tyrosine kinase inhibitors (TKIs) treatment have mainly concentrated on two main aspects: the leukemia stem cells (LSCs) and the tumor microenvironment. However, whether relapse or non-relapse patients who discontinued TKIs therapy, LSCs are still exist. Among a variety of factors that compose the CML microenvironment, myeloid-derived suppressor cells (MDSC) are considered to be a strong contributor to the immunosuppressive tumor microenvironment. Here, we designed the study to investigate the potential relation between tumor cells and MDSC in CML and find risk factors for relapse after discontinuation. We detected the percentage of MDSC and the BCR-ABL (IS) transcript levels in bone marrow of 50 CML patients in chronic phase at our center. The data indicated that the frequency of MDSC had significant positive correlation with BCR-ABL (IS) transcript levels (Figure 1A). In addition, the counts of MDSC had significant difference at different response stages (Figure 1B), especially the M-MDSC, a subtype of MDSC. The percentage of M-MDSC was significantly higher in patients with newly diagnosed or complete hematological response (CHR) or major molecular response (MMR) compared with those of CML patients obtained complete molecular response (CMR) (Figure 1C). When K562 cells or CD34+ cells were cocultured with M-MDSC at a 1:10 ratio, K562 cells or CD34+ cells proliferated significantly at day 3 (Figure 1D and E). K562 subcutaneous tumor formation in BALB/c node mice confirmed that tumors weight and volume of the coculture group were higher than control. Then, we further investigated whether tumor cells have an impact on MDSC through microvesicles (MV). After adding K562-MV to peripheral blood mononuclear cells (PBMCs) from healthy donors, MDSC counts appeared significantly elevated in the different K562 cells counts group compared to the control group (Figure 1F).To analyze the roles of K562-MV collected before and after TKIs discontinuation on MDSC, we established a TKIs discontinuation model using the K562 cell, which emulates the cessation of TKIs treatment of CML patients in some extent. The results showed that regardless of the Imatinib or Dasatinib treatment, a significant increase was observed in the proportion of MDSC after TKIs treatment cessation compared with the TKIs treatment groups (Figure 1G). Experiments in vivo also proved K562-MV after different treatments promoted the proliferation of MDSC (Figure 1H and I). In conclusion, our study introduces the notion of the role of MDSC as mediators in the cross talk between tumor cells and the microenvironment. MDSC would provide a novel and useful model to predict the relapse of CML by establishing a type of new risk stratification system. MDSC could be also act as a promising target in the relapse of CML. In addition, we found a mutual promotion of proliferation of tumor cells and MDSC, this bidirectional interaction results in a vicious cycle by providing a protective niche against immune attacks. Therapeutic interventions modulating this interaction might accelerate the success of treatment-free remission. Figure 1 Disclosures No relevant conflicts of interest to declare.

755 CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A803-A803 ◽  
Author(s):  
Alvaro Teijeira ◽  
Saray Garasa ◽  
Itziar Migueliz ◽  
Assunta Cirella ◽  
Ignacio Melero
Keyword(s):  
Cancer Patients ◽  
Tumor Cells ◽  
Mouse Models ◽  
Chemokine Receptor ◽  
Suppressor Cells ◽  
Neutrophil Extracellular Traps ◽  
Myeloid Derived Suppressor Cells ◽  
Extracellular Traps ◽  
Tumor Associated Neutrophils

BackgroundNeutrophils are expanded and abundant in an important fraction (up to 35% of patients) in cancer-bearing hosts. When neutrophils are expanded, they usually promote exert immunomodulatory functions promoting tumor progression and the generation of metastases. Neutrophils can undergo a specialized form of cell death called NETosis that is characterized by the extrusion of their DNA to contain infections. In cancer NETs have been described to promote metastases in mouse models. IL-8, a CXCR1/2 ligand clinically targeted by blocking antibodies, has been described to induce NETosis and is upregulated in many cancer patients. Our hypothesis is that chemokines secreted by cancer cells can mediate NETosis in tumor associated neutrophils and that NETs can be one of the immunomodulatory mechanisms provided by tumor associated neutrophils.MethodsNETosis induction of peripheral neutrophils and granulocytic myeloid derived suppressor cells by different chemotactic stimuli, tumor cell supernatants and cocultures upon CXCR1/2 blockade. NET immunodetection in mouse models and xenograft tumors upon CXCR1/2 blockade. In vitro tumor cytotoxicity assays in the presence/absence of NETs, and videomicroscopy studies in vitro and by intravital imaging to test NETs inhibition of immune cytotoxicity by immune-cell/target-cell inhibition. Tumor growth studies and metastases models in the presence of NETosis inhibitors and in combination with checkpoint blockade in mouse cancer models.ResultsUnder the influence of CXCR1 and CXCR2 chemokine receptor agonists and other chemotactic factors produced by tumors, neutrophils, and granulocytic myeloid-derived suppressor cells (MDSCs) from cancer patients extrude their neutrophil extracellular traps (NETs). In our hands, CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted NETosis. NETs wrap and coat tumor cells and shield them from cytotoxicity, as mediated by CD8+ T cells and natural killer (NK) cells, by obstructing contact between immune cells and the surrounding target cells. Tumor cells protected from cytotoxicity by NETs underlie successful cancer metastases in mice and the immunotherapeutic synergy of protein arginine deiminase 4 (PAD4) inhibitors, which curtail NETosis with immune checkpoint inhibitors. Intravital microscopy provides evidence of neutrophil NETs interfering cytolytic cytotoxic T lymphocytes (CTLs) and NK cell contacts with tumor cells.ConclusionsCXCR1 and 2 are the main receptors mediating NETosis of tumor associated neutrophils in our in-vitro and in vivo systems expressing high levels of CXCR1 and 2 ligands. NETs limit cancer cell cytotoxicity by impeding contacts with cancer cells.

scholarly journals Rgs2 Mediates Pro-Angiogenic Function of Myeloid Derived Suppressor Cells in the Tumor Microenvironment via Upregulation of MCP-1

PLoS ONE ◽  
2011 ◽  
Vol 6 (4) ◽  
pp. e18534 ◽  
Author(s):  
Kimberly C. Boelte ◽  
Laura E. Gordy ◽  
Sebastian Joyce ◽  
Mary Ann Thompson ◽  
Li Yang ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells
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