Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 14 de 14
Filter
1.
Article in Chinese | WPRIM | ID: wpr-921557

ABSTRACT

Objective To determine whether the signaling activation of bone morphogenetic protein 2(BMP2)can induce myeloid-derived suppressor cells(MDSC)to secret transforming growth factor β(TGF-β),further enhancing the differentiation and infiltration of regulatory T lymphocytes(Treg)into tumor tissue. Methods The BMP2-induced mRNA and protein expression of TGF-β in MDSC was detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay(ELISA),respectively.The effect of BMP2-induced TGF-β secretion by MDSC on Treg differentiation was then determined by flow cytometry.Finally,we implanted the recombined human bone morphogenetic protein 2(rhBMP2)collagen gels into tumor-burdened mice to examine the role of BMP2 in Treg differentiation via MDSC-secreted TGF-β


Subject(s)
Animals , Bone Morphogenetic Protein 2 , Cell Differentiation , Mice , Myeloid-Derived Suppressor Cells , Neoplasms , T-Lymphocytes, Regulatory , Transforming Growth Factor beta
2.
Article in Chinese | WPRIM | ID: wpr-887878

ABSTRACT

Breast cancer patients with bone,liver and lung metastases tend to have a poor prognosis.According to Paget's "seed and soil" theory,metastatic cancer cell "seeds" must fall on congenial target organ "soil".Studies have shown that myeloid-derived suppressor cells(MDSCs)can be recruited at the site of breast cancer metastasis in advance and play a role in the metastasis of breast cancer cells.This paper reviews the biological characteristics of MDSCs,the roles of MDSCs in peripheral circulation,prometastatic niche,and metastatic site during breast cancer metastasis,as well as the research progress of MDSCs-targeted treatment of breast cancer metastasis.


Subject(s)
Breast Neoplasms , Female , Humans , Lung Neoplasms , Myeloid-Derived Suppressor Cells , Neoplasm Metastasis , Tumor Microenvironment
3.
Frontiers of Medicine ; (4): 232-251, 2021.
Article in English | WPRIM | ID: wpr-880952

ABSTRACT

In recent years, studying the role of myeloid-derived suppressor cells (MDSCs) in many pathological inflammatory conditions has become a very active research area. Although the role of MDSCs in cancer is relatively well established, their role in non-cancerous pathological conditions remains in its infancy resulting in much confusion. Our objectives in this review are to address some recent advances in MDSC research in order to minimize such confusion and to provide an insight into their function in the context of other diseases. The following topics will be specifically focused upon: (1) definition and characterization of MDSCs; (2) whether all MDSC populations consist of immature cells; (3) technical issues in MDSC isolation, estimation and characterization; (4) the origin of MDSCs and their anatomical distribution in health and disease; (5) mediators of MDSC expansion and accumulation; (6) factors that determine the expansion of one MDSC population over the other; (7) the Yin and Yang roles of MDSCs. Moreover, the functions of MDSCs will be addressed throughout the text.


Subject(s)
Biology , Humans , Myeloid-Derived Suppressor Cells , Neoplasms
4.
Article in Chinese | WPRIM | ID: wpr-880116

ABSTRACT

OBJECTIVE@#To investigate the effect of expression level changes of monocytic myeloid-derived suppressor cells (M-MDSC) to related immune function in the patients with primary immune thrombocytopenia (ITP).@*METHODS@#Peripheral blood samples were collected from 53 newly diagnosed ITP patients and 30 healthy volunteers. The quantity of M-MDSC, mRNA levels of Arg-1 and iNOS were detected. CD4@*RESULTS@#The count of M-MDSC in peripheral blood of newly diagnosed ITP patients was significantly higher than that in the control group (P < 0.01). However, the expression level of Arg-1 in peripheral blood was not significantly different between the newly diagnosed ITP group and the control group. But the expression level of iNOS in the newly diagnosed ITP patients was significantly higher than that in the control group (P < 0.01). After treatment, the count of M-MDSC in the patients with ITP was significantly lower than before treatment (P < 0.01), which showed that M-MDSC could significantly inhibit the proliferation and secretion of IFN-γ in CD4@*CONCLUSION@#M-MDSC may be related to the disorder of immune tolerance in the patients with ITP, and may become a new index to monitor the curative efficacy of ITP patients.


Subject(s)
Flow Cytometry , HLA-DR Antigens , Humans , Immunity , Myeloid-Derived Suppressor Cells , Purpura, Thrombocytopenic, Idiopathic
5.
Chinese Medical Journal ; (24): 334-343, 2020.
Article in English | WPRIM | ID: wpr-877961

ABSTRACT

BACKGROUND@#High agglomeration of myeloid-derived suppressor cells (MDSCs) in neuroblastoma (NB) impeded therapeutic effects. This study aimed to investigate the role and mechanism of targeted inhibition of MDSCs by low-dose doxorubicin (DOX) to enhance immune efficacy in NB.@*METHODS@#Bagg albino (BALB/c) mice were used as tumor-bearing mouse models by injecting Neuro-2a cells, and MDSCs were eliminated by DOX or dopamine (DA) administration. Tumor-bearing mice were randomly divided into 2.5 mg/kg DOX, 5.0 mg/kg DOX, 50.0 mg/kg DA, and control groups (n = 20). The optimal drug and its concentration for MDSC inhibition were selected according to tumor inhibition. NB antigen-specific cytotoxic T cells (CTLs) were prepared. Tumor-bearing mice were randomly divided into DOX, CTL, anti-ganglioside (GD2), DOX+CTL, DOX+anti-GD2, and control groups. Following low-dose DOX administration, immunotherapy was applied. The levels of human leukocyte antigen (HLA)-I, CD8, interleukin (IL)-2 and interferon (IFN)-γ in peripheral blood, CTLs, T-helper 1 (Thl)/Th2 cytokines, perforin, granzyme and tumor growth were compared among the groups. The Wilcoxon two-sample test and repeated-measures analysis of variance were used to analyze results.@*RESULTS@#The slowest tumor growth (F = 6.095, P = 0.018) and strongest MDSC inhibition (F = 14.632, P = 0.001) were observed in 2.5 mg/kg DOX group. Proliferation of T cells was increased (F = 448.721, P < 0.001) and then decreased (F = 2.047, P = 0.186). After low-dose DOX administration, HLA-I (F = 222.489), CD8 (F = 271.686), Thl/Th2 cytokines, CD4+ and CD8+ lymphocytes, granzyme (F = 2376.475) and perforin (F = 488.531) in tumor, IL-2 (F = 62.951) and IFN-γ (F = 240.709) in peripheral blood of each immunotherapy group were all higher compared with the control group (all of P values < 0.05). The most significant increases in the aforementioned indexes and the most notable tumor growth inhibition were observed in DOX+anti-GD2 and DOX+CTL groups.@*CONCLUSIONS@#Low-dose DOX can be used as a potent immunomodulatory agent that selectively impairs MDSC-induced immunosuppression, thereby fostering immune efficacy in NB.


Subject(s)
Animals , Doxorubicin/therapeutic use , Mice , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells , Neuroblastoma/drug therapy , Tumor Microenvironment
6.
Article in Chinese | WPRIM | ID: wpr-774176

ABSTRACT

Glioma is one of the most common primary tumors in the human brain with poor prognosis. The local and systemic immunosuppressive environment created by glioma cells enables them to evade immunosurveillance. Myeloid-derived suppressor cells (MDSCs) are a critical component of the immunosuppression system. They are a heterogeneous cell population composed of early myeloid progenitor cells and precursor cells. Although the cells are diverse in phenotypes and functions, they all have strong immunosuppressive functions. MDSCs are extensively infiltrated into tumor tissues and play an important role in the glioma immunosuppressive microenvironment, which also hinders the immunotherapeutic effects of glioma. This article will review the phenotypic characteristics of MDSCs in the glioma microenvironment and their role in the progression of glioma. It is of positive significance to better understand the pathogenesis of glioma and explore effective comprehensive treatments.


Subject(s)
Glioma , Pathology , Humans , Immune Tolerance , Myeloid-Derived Suppressor Cells , Cell Biology , Tumor Microenvironment
7.
Article in Chinese | WPRIM | ID: wpr-771879

ABSTRACT

OBJECTIVE@#To investigate the role of myeloid-derived suppressor cells (MDSC) in the prognosis of patients with diffuse large B cell lymphoma (DLBCL).@*METHODS@#The peripheral blood of 52 DLBCL patients and 30 healthy volunteers was collected. The CD14HLA-DR was used as the immune marker for MDSC. The role of MDSC in the prognosis of DLBCL patients was analyzed by combination with the related clinicopathological data.@*RESULTS@#The proportion of MDSC in peripheral blood of newly diagnosed DLBCL patients increased significantly (P<0.01). The expression of MDSC in DLBCL patients was related with clinical staging, lactate dehydrogenase (LDH) level and IPI score (P<0.01). There was no significant correlation with sex, age, and B symptoms. Univariate analysis showed that the clinical stage, serum LDH level, IPI score and MDSC level were the adverse factors affecting the overall survival (OS). Multivariate analysis showed that IPI score and MDSC level were independent risk factors for OS in DLBCL patients.@*CONCLUSION@#MDSC can be used as an important index to evaluate the prognosis of DLBCL patients, contributing to evaluate the immune and tumor microenvironment of DLBCL patients.


Subject(s)
Biomarkers , HLA-DR Antigens , Humans , Lipopolysaccharide Receptors , Lymphoma, Large B-Cell, Diffuse , Myeloid-Derived Suppressor Cells , Prognosis , Tumor Microenvironment
8.
Einstein (Säo Paulo) ; 17(2): eRB4733, 2019. graf
Article in English | LILACS | ID: biblio-1001908

ABSTRACT

ABSTRACT Healthy aging is partly related to appropriate function of the immune system. As already reported, some changes in this system are observed, including reduced number and repertoire of T cells due to thymic involution, accumulation of memory T cells by chronic infections, homeostatic proliferation compensating for the number of naïve T cells, decreased proliferation of T cells against a stimulus, telomere shortening, replicative senescence of the T cells, and inflammaging, besides the accumulation of myeloid-derived suppressor cells. The purpose of this article is to clarify each of these changes, aiming to minimize limitations of immunosenescence. If such associations can be established, these cells may be used as early and less invasive markers of aging-related diseases, as well as to indicate interventions, evaluate the efficacy of interventions and be a tool to achieve longevity with quality of life.


RESUMO O envelhecimento saudável está relacionado, pelo menos em parte, com a função adequada do sistema imunológico. Isso porque já foi relatado que, com o envelhecimento, algumas mudanças desse sistema são observadas, como a diminuição da percentagem e do repertório de células T pela involução tímica, acúmulo de células T de memória por infecções crônicas, compensação do número de células T naïve por proliferação homeostática, diminuição da capacidade de proliferação das células T frente a um estímulo, encurtamento dos telômeros, senescência replicativa das células T, e inflammaging, além do acúmulo de células mieloides supressoras. Este artigo visa esclarecer cada uma das mudanças, mencionadas, com o intuito de buscar meios de minimizar as limitações da imunosenescência. Caso seja possível estabelecer tais relações, essas células podem ser utilizadas como marcadores precoces e pouco invasivos de doenças relacionadas ao envelhecimento, além da possibilidade de serem utilizadas para indicar intervenções, avaliar a eficácia das intervenções e como ferramenta para alcance da longevidade com qualidade de vida.


Subject(s)
Humans , Aging/immunology , T-Lymphocytes/physiology , Immunosenescence/immunology , Myeloid-Derived Suppressor Cells/physiology , Adaptation, Physiological/immunology , Cell Proliferation/physiology
9.
Journal of Experimental Hematology ; (6): 1151-1155, 2018.
Article in Chinese | WPRIM | ID: wpr-689514

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the number of myeloid-derived suppressor cells(MDSC) and the level of prostaglandin E2(PGE2) in the bone marrow of adult ITP patients, and to explore their possible mechanisms involved in the pathogenesis of this disease.</p><p><b>METHODS</b>Twenty-five patients of newly diagnosed ITP, 25 patients of complete remission group and 15 patients of control group were selected. The number of MDSC in the bone marrow between 3 groups was detect by flow cytometry (FCM). The serum level of prostaglandin E2 (PGE2) in 3 groups was determined by enzyme linked immunosorbent assay (ELISA). The relative expression of IFN-γ mRNA in bone marrow mononuclear cells was measured by real time fluorescence quantitative polymerase chain reaction (RT-qPCR) in each groups.</p><p><b>RESULTS</b>The number of MDSC in the complete remission group was significantly higher than that in the control group (P<0.05); the number of MDSC in the newly diagnosed group was higher than that in the control group; the number of MDSC in the complete remission group was higher than that in the newly diagnosed group. The serum level of PGE2 in bone marrow of ITP patients in the newly diagnosed group was higher than that of the control group(P<0.05). The serum level of PGE2 in the bone marrow of ITP patients of the complete remission group was higher than that of the control group (P<0.05). The level of PGE2 in bone marrow serum of ITP patients of the newly diagnosed group was lower than that in the complete remission group(P<0.05). The relative expression level of IFN-gamma in bone marrow mononuclear cells of the ITP patients in newly diagnosed group was higher than that in the control group and the complete remission group(P<0.001). The relative quantification (RQ) of IFN-γ in bone marrow mononuclear cells was 2.60 between the newly diagnosed group and the complete remission group.</p><p><b>CONCLUSION</b>When adult ITP disease is remitted, the number of MDSC rises and correlates with the therapeutic response and PGE2 level in the bone marrow.</p>


Subject(s)
Adult , Bone Marrow , Flow Cytometry , Humans , Myeloid-Derived Suppressor Cells , Purpura, Thrombocytopenic, Idiopathic , RNA, Messenger
10.
Article in English | WPRIM | ID: wpr-776917

ABSTRACT

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8 T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8 T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.


Subject(s)
Animals , Antineoplastic Agents , CD8-Positive T-Lymphocytes , Allergy and Immunology , Carcinoma, Lewis Lung , Drug Therapy , Genetics , Allergy and Immunology , Cell Line, Tumor , Cisplatin , Abietanes , Drug Synergism , Humans , Interferon-gamma , Genetics , Allergy and Immunology , Lung Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , Matrix Metalloproteinase 9 , Genetics , Mice , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells , Allergy and Immunology , Plant Extracts , Rosmarinus , Chemistry
11.
Article in English | WPRIM | ID: wpr-812339

ABSTRACT

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8 T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8 T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.


Subject(s)
Abietanes , Animals , Antineoplastic Agents , CD8-Positive T-Lymphocytes , Allergy and Immunology , Carcinoma, Lewis Lung , Drug Therapy , Genetics , Allergy and Immunology , Cell Line, Tumor , Cisplatin , Drug Synergism , Humans , Interferon-gamma , Genetics , Allergy and Immunology , Lung Neoplasms , Drug Therapy , Genetics , Allergy and Immunology , Matrix Metalloproteinase 9 , Genetics , Mice , Mice, Inbred C57BL , Myeloid-Derived Suppressor Cells , Allergy and Immunology , Plant Extracts , Rosmarinus , Chemistry
12.
Braz. j. med. biol. res ; 50(2): e5637, 2017. tab, graf
Article in English | LILACS | ID: biblio-839249

ABSTRACT

Immune thrombocytopenia (ITP) is a disease characterized by isolated thrombocytopenia. Abnormal effector T cell activation is an important mechanism in the pathogenesis of ITP. Regulatory T cells (Treg) have a strong immunosuppressive function for T cell activation and their importance in the pathophysiology and clinical treatment of ITP has been confirmed. Myeloid-derived suppressor cells (MDSCs) are other immunosuppressive cells, which can also suppress T cell activation by secreting arginase, iNOS and ROS, and are essential for Treg cells’ differentiation and maturation. Therefore, we speculate that MDSCs might also be involved in the immune-dysregulation mechanism of ITP. In this study, we tested MDSCs and Treg cells in peripheral blood samples of twenty-five ITP patients and ten healthy donors. We found that MDSCs and Treg cells decreased simultaneously in active ITP patients. Relapsed ITP patients showed lower MDSCs levels compared with new patients. All patients received immunosuppressive treatment including dexamethasone alone or in combination with intravenous immune globulin. We found that MDSCs’ level after treatment correlated with platelet recovery. Our study is the first that focused on MDSCs’ role in ITP. Based on our results, we concluded that circulating MDSCs could predict disease activity and treatment response in ITP patients. This preliminary conclusion indicates a substantial significance of MDSCs in the pathophysiology and clinical treatment of ITP, which deserves further investigation.


Subject(s)
Humans , Male , Female , Adult , Myeloid-Derived Suppressor Cells/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , T-Lymphocytes, Regulatory/immunology , Case-Control Studies , Dexamethasone/administration & dosage , Immunoglobulins, Intravenous/administration & dosage , Lymphocyte Activation , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/physiopathology , T-Lymphocytes, Regulatory/physiology
13.
Article in English | WPRIM | ID: wpr-285216

ABSTRACT

The function of the spleen in tumor development has been investigated for years. The relationship of the spleen with hepatocellular carcinoma (HCC), a huge health burden worldwide, however, remains unknown. The present study aimed to examine the effect of splenectomy on the development of HCC and the possible mechanism. Mouse hepatic carcinoma lines H22 and Hepa1-6 as well as BALB/c and C57 mice were used to establish orthotopic and metastatic mouse models of liver cancer. Mice were divided into four groups, including control group, splenectomy control group (S group), tumor group (T group) and tumor plus splenectomy group (T+S group). Tumor growth, metastases and overall survival were assessed at determined time points. Meanwhile, myeloid-derived suppressor cells (MDSCs) were isolated from the peripheral blood (PB), the spleen and liver tumors, and then measured by flow cytometery. It was found that liver cancer led to splenomegaly, and increased the percentage of MDSCs in the PB and spleen in the mouse models. Splenectomy inhibited the growth and progression of liver cancer and prolonged the overall survival time of orthotopic and metastatic models, which was accompanied by decreased proportion of MDSCs in the PB and tumors of liver cancer-bearing mouse. It was suggested that splenectomy could be considered an adjuvant therapy to treat liver cancer.


Subject(s)
Animals , Carcinoma, Hepatocellular , General Surgery , Cell Line, Tumor , Flow Cytometry , Humans , Liver Neoplasms , General Surgery , Mice , Myeloid-Derived Suppressor Cells , Pathology , Neoplasms, Experimental , General Surgery , Spleen , General Surgery , Splenectomy , Methods
14.
Article in Chinese | WPRIM | ID: wpr-317761

ABSTRACT

<p><b>OBJECTIVE</b>To explore the myeloid-derived suppressor cell (MDSC) expression in the peripheral blood and lesions of 4NQO-induced tongue carcinoma in mouse.</p><p><b>METHODS</b>The established 4NQO mouse model was used to analyze the distribution of MDSC and T cell subsets in the peripheral blood by flow cytometry. The relations of MDSC with T cell subsets and CD4⁺/CD8⁺ changes were evaluated. The distribution of MDSC in the lesions of tongues was analyzed by immu- nohistochemistry, and the expression of arginase 1 (ARG-1) in tongue tissues was detected by real-time polymerase chain reaction.</p><p><b>RESULTS</b>During tumor progression, a significant increase was observed in the frequency of MDSC in the peripheral blood of 4NQO treated mice (P < 0.01). The frequency of MDSC was positively correlated with systemic CD3⁺CD8+T cells but negatively correlated with the CD4⁺/CD8⁺ ratio. Squamous cell carcinomas were extensively infiltrated with MDSC, whereas dysplastic area and normal tongue mucosa had only sparse MDSC infiltration. The majority of MDSCs were located in the stroma, particularly along the tumor invasive front. Moreover, 4NQO-treated mice showed significantly higher ARG-1 mRNA levels in the tumor site (P<0.01).</p><p><b>CONCLUSION</b>MDSC may contribute to oral tumor progression and represents a potential target for immunotherapy of oral cancer.</p>


Subject(s)
4-Nitroquinoline-1-oxide , Animals , Arginase , Cell Count , Flow Cytometry , Mice , Models, Animal , Myeloid-Derived Suppressor Cells , Allergy and Immunology , Real-Time Polymerase Chain Reaction , T-Lymphocyte Subsets , Allergy and Immunology , Tongue Neoplasms , Allergy and Immunology
SELECTION OF CITATIONS
SEARCH DETAIL