Research progress of myeloid-derived suppressor cells in tumor angiogenesis / 国际肿瘤学杂志

As a kind of immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) are an important component of the immune microenvironment. MDSCs play a significant role in promoting tumor immune escape. In addition, non-immunological functions such as promoting angiogenesis can also promote tumor development with the deepening of research. MDSCs can promote tumor angiogenesis directly through vascular endothelial growth factor signaling pathway, or promote tumor growth and angiogenesis by secreting cytokines such as matrix metalloprotein-9, basic fibroblast growth factor, angiogenic peptide Bv8, platelet derived growth factor, exosomes, or interacting with other cells. Exploring the expansion, activation, recruitment and angiogenesis mechanism of MDSCs will provide new ideas for regulating the individualized diagnosis and treatment based on targeted MDSCs.

Research Progress of Granulocytic Myeloid-derived Suppressor Cells in Non-small Cell Lung Cancer / 中国肺癌杂志

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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Células supressoras mieloides derivadas dois anos após a erradicação do vírus da hepatite C usando antivirais de ação direta / Myeloid-derived suppressor cells two years after hepatitis c virus eradication using directly acting antivirals

ABSTRACT Background: Myeloid-derived suppressor cells (MDSCs) have immature morphology, relatively weak phagocytic activity, as well as some immunosuppressive functions. The capacity of MDSCs to inhibit T-cell-mediated immunological responses is their most notable functional characteristic. Down-regulating antitumor immune surveillance is one way that the expansion and activation of MDSCs contribute significantly to the occurrence and progression of tumors. Increased levels of MDSCs in patients with chronic hepatitis C virus (HCV) infection could suppress T-cell responses, promoting viral escape and hepatitis progression. This may make HCV-infected individuals more vulnerable to severe infections, hepatic and extra-hepatic tumors, and a diminished capacity to react to immunization. It is still unknown if effective HCV eradication with directly acting antivirals (DAAs) can restore immune functions and immune surveillance capacity. Objective: The purpose of this study was to observe the frequency of M-MDSCs (CD33+, CD11b+, and HLA-DR) in patients with a previous history of HCV, 2-3 years after virus eradication using DAA therapy. Methods: This study was conducted on 110 subjects: fifty-five subjects without liver cirrhosis who were treated with HCV using DAAs and attained SVR for a period of 2-3 years and 55 age- and gender-matched healthy controls. The study was conducted during the period from January to July 2022. Patients were recruited from the National Viral Hepatitis Treatment Unit, Alexandria University Hepatology outpatient clinic, and the Alexandria University Tropical Medicine outpatient clinic. The frequencies of MDSCs (CD33+CD11b + HLA-DR-) by flow cytometry were assessed. Results: Even after the virus had been eradicated for longer than two years, MDSC levels in HCV-treated individuals were found to be considerably higher. In the HCV-treated group, the median number of MDSCs was 5, with an interquartile range (IQR) of 3.79-7.69. In contrast, the median for the control group was 3.1, with an IQR of 1.4-3.2 (P˂0.001). Conclusion: Successful DAA therapy leads to slow and partial immunological reconstitution, as demonstrated by the failure to attain normal levels of MDSC's 2 years after successful HCV eradication despite the normalization of laboratory parameters as well as the absence of liver fibrosis. The clinical implications of these findings should be thoroughly studied.

RESUMO Contexto: As células supressoras derivadas de mieloides (CSDMs) possuem morfologia imatura, atividade fagocítica relativamente fraca e algumas funções imunossupressoras. A capacidade das CSDMs de inibir respostas imunológicas mediadas por células T é sua característica funcional mais notável. A expansão e ativação das CSDMs contribuem significativamente para a ocorrência e progressão de tumores, regulando negativamente a vigilância imunológica antitumoral. Níveis aumentados de CSDMs em pacientes com infecção crônica pelo vírus da hepatite C (HCV) poderiam suprimir respostas das células T, promovendo a fuga viral e a progressão da hepatite. Isso pode tornar os indivíduos infectados pelo HCV mais vulneráveis a infecções graves, tumores hepáticos e extra-hepáticos, e a uma capacidade diminuída de reagir à imunização. Ainda não se sabe se a erradicação eficaz do HCV com antivirais de ação direta (AAD) pode restaurar as funções imunológicas e a capacidade de vigilância imunológica. Objetivo: O objetivo deste estudo foi observar a frequência de M-CSDMs (CD33+, CD11b+ e HLA-DR-) em pacientes com histórico anterior de HCV, 2-3 anos após a erradicação do vírus usando terapia com AADs. Métodos: Este estudo foi realizado em 110 indivíduos: 55 indivíduos sem cirrose hepática que foram tratados com AADs para HCV e atingiram resposta virológica sustentada (SVR) por um período de 2-3 anos e 55 controles saudáveis pareados por idade e gênero. O estudo foi conduzido no período de janeiro a julho de 2022. Os pacientes foram recrutados da Unidade Nacional de Tratamento de Hepatites Virais, da clínica ambulatorial de Hepatologia da Universidade de Alexandria e da clínica ambulatorial de Medicina Tropical da Universidade de Alexandria. As frequências de CSDMs (CD33+CD11b+HLA-DR-) foram avaliadas por citometria de fluxo. Resultados: Mesmo após a erradicação do vírus por mais de dois anos, os níveis de CSDMs em indivíduos tratados para HCV foram consideravelmente mais altos. No grupo tratado para HCV, o número mediano de CSDMs foi de 5, com um intervalo interquartil (IQR) de 3,79-7,69. Em contraste, a mediana para o grupo controle foi de 3,1, com um IQR de 1,4-3,2 (P<0,001). Conclusão: A terapia bem-sucedida com AADs leva a uma reconstituição imunológica lenta e parcial, como demonstrado pela falha em atingir níveis normais de CSDMs 2 anos após a erradicação bem-sucedida do HCV, apesar da normalização dos parâmetros laboratoriais e da ausência de fibrose hepática. As implicações clínicas desses achados devem ser estudadas minuciosamente.

Advances on myeloid-derived suppressor cells in hepatitis B virus infection / 中华临床感染病杂志

Myeloid-derived suppressor cells (MDSCs) are a group of immature and heterogeneous cells that can inhibit T cell function. In pathological conditions such as tumors, infections, and chronic inflammation, the large expansion of MDSCs is involved in processes of immune escape, immune tolerance and inflammatory reactions. MDSCs are also crucial in the pathophysiology of hepatitis B virus (HBV) infection, however, their activation, differentiation, and function during HBV infection are still unclear. This article reviews the general characteristics and roles of MDSCs in HBV infection, as well as related drug therapies, in order to provide information for further research on the related mechanism and potential targeted treatment.

The role of myeloid-derived suppressor cells in chronic osteomyelitis / 免疫学杂志

Inhibitory cells derived from bone marrow are a kind of inhibitory cells derived from bone marrow.These cells are not only related to tumor growth,but also participate in the inflammatory immune process.Therefore,we established a rat model of chronic osteomyelitis,and used gemcitabine to inhibit the cell growth ratio of MDSCs.We detected the ratio of MDSCs in bone marrow and spleen of rats by flow cytometry and immunofluorescence,detected the changes of inflammatory factors in peripheral blood by ELISA,and analyzed the inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-11)in peripheral blood of normal rats,osteomyelitis rats and rats after gemcitabine inhibition.The results showed that the proportion of MDSCs cells in bone marrow and spleen of osteomyelitis model rats was increased,but it was significantly decreased in gemcitabine group(P<0.05).Levels of inflammatory factors(TNF-α,PCT,IL-4,IL-10,IL-17,IFN-γ,TGF-β)were positively correlated with the change of MDSCs cell proportion(P<0.05).From the results,it can be inferred that the change of the proportion of MDSCs cells in rat osteomyelitis is positively related to the inflammatory factors,and gemcitabine can reduce inflammatory factors by inhibiting MDSCs.

Effect of myeloid-derived suppressor cells reduced by anti-Gr-1 antibody on CD8 + T cell number and tumor growth / 肿瘤研究与临床

Objective:To explore the effects of reducing myeloid-derived suppressor cells (MDSC) of Lewis lung cancer mice by anti-Gr-1 antibody on tumor growth and CD8 + T cell number in peripheral blood, spleen and tumor tissues. Methods:A mouse Lewis lung cancer cells tumor-bearing mouse model was constructed. MDSC were reduced by intraperitoneal injection of anti-Gr-1 antibody every 48 h (observation group), and model mice injected with equal amount of 0.7% NaCl solution were used as control group, and the injections lasted for 3 weeks. Three mice were killed on days 7, 14 and 21 after tumor inoculation. Flow cytometry was applied to dynamically monitor the proportions of MDSC and CD8 + T cells in the peripheral blood, spleen and tumor tissues of mice at different time points. Seven days after tumor inoculation, the longest and shortes diameters of subcutaneous tumors in mice were measured at regular intervals to monitor the tumor size of both groups. Results:The tumor volume in both groups increased with the extension of time, and the increase trend in the observation group was relatively slow. On day 20, the tumor volume in the observation group was smaller than that in the model group [(1 978±315) mm 3 vs. (1 356±432) mm 3, P = 0.001]. On days 7, 14 and 21 after tumor inoculation, the proportions of MDSC and CD8 + T cells in the peripheral blood, spleen and tumor tissues of mice of the observation group were lower than those of the control group. The proportion of MDSC in the peripheral blood of mice of both groups showed an upward trend over time, with the observation group showing a slower upward trend than the control group. The proportion of CD8 + T cells in the peripheral blood of both groups showed an upward trend from day 7 to day 14, and the observation group showed a more significant upward trend. The proportion of CD8 + T cells in both groups showed a downward trend from day 14 to day 21. The changes in the proportions of MDSC and CD8 + T cells in the spleen of mice of both groups were similar to those in the peripheral blood, but the proportion of CD8 + T cells in the control group showed a more significant upward trend than the observation group from day 7 to day 14. The proportion of MDSC cells in the tumor tissues of the control group showed a significant upward trend from day 7 to day 14, and stabilized from day 14 to day 21. The proportion of MDSC cells in the observation group slowly increased from day 7 to day 14, and decreased from day 14 to day 21. The proportion of CD8 + T cells in both groups showed an upward trend from day 7 to day 14, and decreased from day 14 to day 21. Conclusions:Anti-Gr-1 antibody can effectively reduce MDSC in the peripheral blood, spleen and tumor tissues of Lewis lung cancer tumor-bearing mice, and inhibit tumor growth, but also reduce the level of CD8 + T cells in the peripheral blood, spleen and tumor tissues.

ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor with an immunosuppressive tumor microenvironment (TME). In this environment, myeloid cells, such as myeloid-derived suppressor cells (MDSCs), play a pivotal role in suppressing antitumor immunity. Lipometabolism is closely related to the function of myeloid cells. Here, our study reports that acetyl-CoA acetyltransferase 1 (ACAT1), the key enzyme of fatty acid oxidation (FAO) and ketogenesis, is significantly downregulated in the MDSCs infiltrated in GBM patients. To investigate the effects of ACAT1 on myeloid cells, we generated mice with myeloid-specific (LyzM-cre) depletion of ACAT1. The results show that these mice exhibited a remarkable accumulation of MDSCs and increased tumor progression both ectopically and orthotopically. The mechanism behind this effect is elevated secretion of C-X-C motif ligand 1 (CXCL1) of macrophages (Mφ). Overall, our findings demonstrate that ACAT1 could serve as a promising drug target for GBM by regulating the function of MDSCs in the TME.

Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on Migration and Invasion of PMN-MDSCs in Gastric Cancer Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang containing intestinal absorption solution （BXCIAS） on migration and invasion of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodThe complex solution （containing 0.63 g·mL-1 crude drug） was prepared. Gastric cancer cells were subjected to non-contact co-culture with PMN-MDSCs in Transwell chamber to create gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of BXCIAS on PMN-MDSCs for subsequent experiment. The blank group， model group， FAK inhibitor group， and BXCIAS groups （26%， 18%， and 10%） were designed. Scratch assay and Transwell assay were employed to detect the migration and invasion ability of PMN-MDSCs， and enzyme-linked immunosorbent assay （ELISA） to measure the expression of vascular endothelial cell growth factor （VEGF） and matrix metalloproteinase-9 （MMP-9） in tumor microenvironment. The expression levels of PMN-MDSCs pathway-related proteins FAK， phosphorylated （p）-FAK， protein tyrosine kinase （Src）， and p-Src were detected by Western blot. ResultThe inhibition rates of PMN-MDSCs by 5%， 50%， 75%， and 100% BXCIAS at 48 h were higher than those at 24 h （P<0.05， P<0.01）. The inhibition rate of PMN-MDSCs by 50% BXCIAS at 72 h was lower than that at 48 h （P<0.01）， and the inhibition rates by 5% and 100% BXCIAS at 72 h were higher than those at 48 h （P<0.05， P<0.01）. There was no significant difference in the inhibition rate by other concentration levels at 48 h. The half-maximal inhibitory concentration （IC50） at 48 h was 18.09%， indicating that 18% BXCIAS and 48 h were the optimal concentration and time， respectively. The migration distance of PMN-MDSCs was large （P<0.01）， and the number of migrating and invading cells increased （P<0.01） in the mode group compared with those in the blank group. Compared with model group， FAK inhibitor and BXCIAS at different concentration decreased the migration distance of PMN-MDSCs （P<0.01）， and the number of migrating and invading cells （P<0.01）， especially the 26% BXCIAS （P<0.01）. The expression of PMN-MDSCs pathway-related proteins FAK， p-FAK， Src and p-Src （P<0.01） and the expression of VEGF and MMP-9 （P<0.01） were higher in the model group than in the blank group. Compared with model group， FAK inhibitor and BXCIAS （26%， 18%， 10%） decreased the expression of FAK， p-FAK， and Src （P<0.01）， and FAK inhibitor and 18% BXCIAS reduced the expression of p-Src （P<0.01）， and the expression of VEGF and MMP-9 （P<0.01）. ConclusionBXCIAS can inhibit the migration and invasion of PMN-MDSCs by down-regulating the expression of FAK， p-FAK， Src， and p-Src proteins in the FAK signaling pathway of PMN-MDSCs in gastric cancer microenvironment.

Effect of Banxia Xiexintang-containing Intestinal Absorption Solution on PMN-MDSCs Apoptosis in Gastric Cancer Microenvironment / 中国实验方剂学杂志

ObjectiveTo observe the effect of Banxia Xiexintang （BXT）-containing intestinal absorption solution on the apoptosis of polymorphonuclear myeloid-derived suppressor cells （PMN-MDSCs） in gastric cancer microenvironment. MethodBXT-containing intestinal absorption solution was prepared， and gastric cancer cells and PMN-MDSCs were non-contact co-cultured in Transwell chamber to establish gastric cancer microenvironment. Cell counting kit-8 （CCK-8） assay was used to screen the optimal intervention concentration and time of 0-100% BXT-containing intestinal absorption solution prepared by 0.63 g·mL-1 reconstitution solution. Cells were classified into blank group， model group， oxaliplatin group （10 mg·L-1）， and BXT （26%， 18%， 10% BXT-containing intestinal absorption solution） group， and the apoptosis of PMN-MDSCs was detected by flow cytometry. The expression of apoptosis-related B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cysteine-aspartic acid protease-3 （Caspase-3） in PMN-MDSCs was detected by Western blot. ResultAfter treatment for 24 h and 48 h， the PMN-MDSCs-inhibiting rate was increased by 5%， 50%， 75%， and 100% BXT-containing intestinal absorption solution compared with that in the blank group （P<0.05， P<0.01）. At 72 h， the PMN-MDSCs-inhibiting rate by 50% BXT-containing intestinal absorption solution was lower than that at 48 h （P<0.01）， and the PMN-MDSCs-inhibiting rate by 5%， 75%， and 100% BXT-containing intestinal absorption solution showed no significant difference from that at 48 h. Moreover， the half-maximal inhibitory concentration （IC50） at 48 h was 18.40%. Thus， 18% BXT-containing intestinal absorption solution and 48 h were the optimal intervention concentration and time. The survival rate of PMN-MDSCs in model group was higher than that in the blank group （P<0.05）， and the apoptosis rate was lower than that in the blank group （P<0.05）. Compared with model group， BXT containing intestinal absorption solution lowered the survival rate and raised apoptosis rate of PMN-MDSCs （P<0.05）， particularly the 26% BXT-containing intestinal absorption solution （P<0.05）. The expression of Bax and Caspase-3 in PMN-MDSCs was lower in the model group than in the blank group （P<0.05）， and the expression of Bcl-2 was higher in the model group than in the blank group （P<0.05）. The expression of Caspase-3 in PMN-MDSCs increased （P<0.05） and the expression of Bcl-2 decreased （P<0.05） in oxaliplatin group and BXT group compared with those in the model group. The expression of Bax rose in oxaliplatin group and BXT group （10% BXT-containing intestinal absorption solution） （P<0.05）. ConclusionBXT can induce the apoptosis of PMN-MDSCs by regulating the expression of apoptosis-related proteins Bax， Caspase-3， and Bcl-2 in gastric cancer microenvironment.

Progress in mechanism of tumor-derived exosomes on myeloid-derived suppressor cells / 中华微生物学和免疫学杂志

Myeloid-derived suppressor cells (MDSCs) play an important immunosuppressive role in the tumor microenvironment. Tumor cells can regulate the immunosuppressive function of MDSCs in the tumor microenvironment through exosomes, thereby affecting the development of tumors. Tumor-derived exosomes (TEXs) promote the development of MDSCs and improve their immunosuppressive function in the tumor microenvironment mainly by participating in the processes such as intercellular information exchange and information transmission. Moreover, the miRNAs in TEXs will also be transferred to recipient cells to inhibit the immunosuppressive function of MDSCs by inducing the negative regulation of target genes. This review summarized the progress in the mechanism of TEXs on MDSCs.

The antitumor activity of hPRDX5 against pancreatic cancer and the possible mechanisms

Recombinant human peroxiredoxin-5 (hPRDX5), isolated from anti-cancer bioactive peptide (ACBPs), shows a homology of 89% with goat peroxiredoxin-5 (gPRDX5) and is reported to display anti-tumor activity in vivo. Herein, we explored the effect of hPRDX5 and the responsible mechanism in treating pancreatic cancer. Tumor-bearing mice were randomly divided into normal PBS group and treatment group (n=5; 10 mg/kg hPRDX5). Flow cytometry was employed to examine lymphocytes, myeloid-derived suppressor cell subsets, and the function proteins of natural killer (NK) cells in peripheral blood, spleen, and tumor tissues of mice. Western blot was used to measure the protein expressions of the key nodes in TLR4-MAPK-NF-κB signaling pathway. The rate of tumor suppression was 57.6% at a 10 mg/kg dose in orthotopic transplanted tumor mice. Moreover, the population of CD3+CD4+T cells, NK cells, and CD3+CD8+T cells was significantly increased in the tumor tissue of the hPRDX5 group, while the proportion of granulocytic-myeloid-derived suppressor cells decreased slightly. In addition, after treatment with hPRDX5, the percentage of NK cells in blood increased more than 4-fold. Our findings indicated that hPRDX5 effectively suppressed pancreatic cancer possibly via the TLR4-MAPK-NF-κB signaling cascade; hence hPRDX5 could be a prospective immunotherapy candidate for treating pancreatic cancer.

Effects of Signaling Activation of Bone Morphogenetic Protein 2 on the Differentiation and Infiltration of Regulatory T Lymphocytes in Tumors / 中国医学科学院学报

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

Role of myeloid-derived suppressor cell in respiratory tract infections / 中华微生物学和免疫学杂志

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of immature myeloid cells that are generated from the blockade differentiation of myeloid cells during pathological conditions. MDSC are regulatory immune cells with a potent immunosuppressive function, and play an important role in the development of various diseases including tumor, autoimmune diseases and trauma. Interestingly, emerging evidence shows that respiratory tract infections by viruses, bacteria and fungi can cause MDSC expansion and activation. MDSC levels are closely related to the symptoms of diseases caused by respiratory pathogens. Further investigation on the role and molecular mechanism of MDSC expansion and activation in respiratory tract infections will contribute to the development of novel strategies for the prevention and treatment of diseases caused by respiratory pathogens. Here, we summarized the role of MDSC in respiratory viral, bacterial and fungal infections and the relevant molecular mechanisms, aiming to provide a reference for further investigating the role of MDSC in respiratory tract infections.

Correlation of peripheral myeloid-derived suppressor cells with hepatitis c virus infection / 中国输血杂志

【Objective】 To investigate the correlation of peripheral myeloid-derived suppressor cells (MDSC) with hepatitis c virus (HCV) infection. 【Methods】 109 voluntary blood donors who donated blood during February 2018 to September 2020 at Guangzhou Blood Center were recruited in this study. They were assigned to chronic hepatitis c (CHC) group (n=48), spontaneous clearance (SC) group (n=29) and healthy donors (control) group (n=32) according to the results of anti-HCV and HCV RNA tests. Blood samples were drawn from the participants and peripheral blood mononuclear cells (PBMC) were freshly isolated, followed by staining with fluorescently-labeled antibody against cell surface markers of MDSC, which were then applied to the detection of monocytic- (M) and polymorphonuclear (PMN)-MDSC by flow cytometry. Parameters for liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL) and direct bilirubin (DBIL) were also measured. One-way ANOVA tests were applied to compare the differences of M- and PMN-MDSC and liver function between three study groups. For pairwise comparisons, P values were adjusted for multiple comparisons by Bonferroni correction (Pc). 【Results】 The frequencies of M-MDSC (%) in CHC, SC and HC were 1.39±0.86, 0.85±0.63 and 0.57±0.23, respectively (P0.05). In addition, AST (34.4±19.2 vs 23.0±7.78 U/L) and GGT (40.8±31.4 vs 22.3±7.40 U/L) level were higher in CHC compared with control (Pc<0.05 and Pc<0.01, respectively). 【Conclusion】 The level of peripheral M-MDSC was significantly elevated in chronic HCV infected donors, which would related to the progression of chronicity after HCV infection.

Influence of hepatocellular carcinoma microenvironment on myeloid-derived suppressor cells / 临床肝胆病杂志

Myeloid-derived suppressor cells (MDSCs) are a group of immature bone marrow cells with an immunosuppressive effect, and they are abundant in tumor patients and can induce tumor cells to escape the killing of immune cells and thus promote the development, progression, and metastasis of tumor. In recent years, its role in hepatocellular carcinoma microenvironment has attracted more and more attention, but the mechanisms of its recruitment and differentiation in hepatocellular carcinoma microenvironment have not been clearly elucidated. This article mainly summarizes the mechanism of action of tumor cells and tumor stromal cells in hepatocellular carcinoma microenvironment (such as hepatic stellate cells, tumor-associated fibroblasts, and tumor-associated endothelial cells) in the recruitment and differentiation of MDSCs, and it is proposed to target MDSCs as an adjuvant therapy to enhance the potential value of immunotherapy for liver cancer.

Roles of Myeloid-derived Suppressor Cells in Breast Cancer Metastasis / 中国医学科学院学报

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.

Advances in research on infection of Myeloid-derived suppressor cells / 医学研究生学报

Myeloid-derived suppressor cells (MDSCs) are newly discovered cells derived from bone marrow that suppress immunity, playing an immunosuppressive role in tumors, infections, and autoimmune diseases. It has been confirmed in disease model studies that their immunosuppressive effect is mainly achieved by suppressing the function of T cells. At present, the treatment of infectious diseases is still a major obstacle, especially in the treatment of chronic infectious diseases. Studies have found that MDSCs have increased aggregation in infectious diseases. As MDSCs are gaining more attention in infectious diseases, their potential therapeutic effects may be further explored. This article mainly reviews the immunosuppressive mechanisms of MDSCs in infections such as bacteria, viruses, parasites and fungi and their relationship with the diseases.

The role and mechanism of myeloid-derived suppressor cells in mice with nonalcoholic steatohepatitis / 中国医师杂志

Objective To investigate the effects of myeloid-derived suppressor cells (MDSCs) on nonalcoholic steatohepatitis mice.Methods (1) Male C57BL/6 mice aged 6-8 weeks were randomly divided into normal diet group,CDAA group(choline deficient amino acid diet) and CSAA group (choline sufficient amino acid diet).(2) After the success of the non-alcoholic steatohepatitis model,serum was collected from some mice to detect biochemical indexes;Liver tissue was retained for microscopic observation by hematoxylin-eosin (HE) staining;The changes of T cell subsets in peripheral blood of mice in each group were detected by flow cytometry.In addition,The proportion and subtype of CD1 lb + Gr-1 + MDSCs cells in liver,spleen,blood and bone marrow were also detected by flow cytometry.(3)The bone marrow-derived Gr-1highLy-6G+ was purified by magnetic bead sorting technique,and the purified Gr-1highLy-6G+ was transferred into non-alcoholic steatohepatitis (NASH) mice by tail vein injection.The role of MDSCs in NASH was analyzed by detection of serological indexes of liver function and pathological dyeing.Results (1) There was no significant difference in body weight and liver index between the groups (P ＞ 0.05).Serological indicators:alanine aminotransferase (ALT),aspartate aminotransferase (AST),blood glucose,interleukin (IL)-6 and interferon-γ (INF-γ) in the model group were significantly higher than those in the normal group (P ＜ 0.01);microscopic findings:the liver in CDAA,CSAA group showed varying degrees of steatosis;the steatosis in CDAA group was much more severe.(2) Flow cytometry showed that ① the percentage of CD4 + CD8-T and CD4-CD8 + T decreased and CD4/CD8 ratio decreased in CDAA group;② the bone marrow MDSCs of CDAA group is lower than that of normal group (P ＜ 0.05);the MDSCs of peripheral blood in CDAA group is lower than that of normal group (P ＞ 0.05);the MDSCs of liver in CDAA group is lower than that of normal group (P ＜ 0.01).③ subgroup comparison,bone marrow,liver CD11 b + Gr-1 high Ly-6G + (G-MDSC):CDAA group ＞ normal group (P ＜ 0.0l),CD11 b + Gr-1 dim Ly-6G-(M-MDSC) showed a downward trend,CDAA group ＜ normal group;(3) Serum AST and ALT levels of NASH mice who receiving Gr-1highLy-6G+ MDSCs from normal bone marrow were significantly decreased (P ＜ 0.001),and histopathological changes were alleviated.Conclusions (1) The NASA mouse model can be successfully established on the CDAA diet.(2) The CDAA-induced NASH mice may have immune dysfunction,mainly manifesting in the change of bone marrow MDSCs subpopulations and the increase of CDllb + Gr-1highLy-6G+ (G-MDSC).(3) MDSCs derived from normal mouse bone marrow can alleviate the pathological changes of NASH.

Function of myeloid-derived suppressor cells and strategy of reversal immunosuppression / 中国肿瘤生物治疗杂志

@#Myeloid-derived suppressor cells (MDSCs) are a group of highly heterogeneous immunosuppressive cells produced in the bone marrow, which accumulate in large amounts under pathological conditions such as malignant tumors. MDSCs are the significant cell subsets that reduce patients' response to traditional treatment and promote tumor progression. In recent years, immune checkpoint blockade and adoptive transfusion of engineered T cells have significantly prolonged the survival of many patients with advanced malignant tumors, but the effective rate from 15% to 40% in some solid tumors including lung cancer, colorectal cancer etc., which is closely related to the immunosuppressive microenvironment in solid cancers. With the accumulation in tumor microenvironment, MDSCs reduce the anti-tumor immune response of patients by inhibiting T cell or NK cell proliferation and function, which is the key mechanism for patients tolerating to immunotherapy. Therefore, clarifying the accumulation and functional characteristics of MDSCs is an important research direction to explore the improvement of restoring immunotherapy. This article will systematically elaborate the regulatory mechanism of MDSC production, aggregation and immunosuppressive function, and outline the latest research progress of targeted MDSC therapy

Predictive Role of Circulating Immune Cell Subtypes Early after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia

BACKGROUND AND OBJECTIVES: Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission. METHODS: Peripheral blood samples were taken at the median of 14 days (range, 12~29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry. RESULTS: The median age was 49.0 years (range, 21~69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8+ T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III–IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091~0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078~0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III–IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse. CONCLUSIONS: iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.