scholarly journals Increased Expression of Myeloid-Derived Suppressor Cells in Patients with HBV-Related Hepatocellular Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tianyu Li ◽  
Xinyu Zhang ◽  
Zhuo Lv ◽  
Li Gao ◽  
Huimin Yan
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Systemic Inflammation ◽  
Cd8 T Cells ◽  
Immune Escape ◽  
Suppressor Cells ◽  
Tumor Burden ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape ◽  
Indirect Bilirubin

Background and Aim. Myeloid-derived suppressor cells (MDSCs) have attracted attention due to their important role in tumor immune escape. Several studies have investigated the involvement of MDSCs into hepatocellular carcinoma (HCC); however, due to the difference of MDSC phenotype, patient types, and sample source among the studies, the results were inconsistent and controversial. The present study aimed to confirm the expression and clinical significance of MDSCs in HBV-related HCC patients. Methods. The percentages of MDSCs, IFN-γ-producing CD4 and CD8 T cells in the peripheral blood of HCC patients, chronic hepatitis B (CHB) patients, and healthy controls (HC) were determined by flow cytometry. The serum concentrations of IL-10 and TNF-α were determined by ELISA. The association of the percentages of MDSCs with tumor burden, liver function parameters, systemic inflammation-related indexes, and IFN-γ-producing T cells was assessed. Results. The percentages of MDSCs and PMN-MDSCs were significantly higher in HCC patients than those in CHB patients and HC. The level of MDSCs was correlated with indirect bilirubin and prealbumin, as well as systemic inflammation response index, monocyte/lymphocyte ratio, and monocyte counts. The frequency of IFN-γ-producing CD8 T cells of HCC patients was lower than that of HC. However, there was no relationship between MDSCs and IFN-γ-producing CD8 T cells. The level of IL-10 in HCC patients was significantly higher than that in CHB patients. Conclusion. MDSCs seem to play an important role in the process leading from chronic HBV infection to HCC. Early inhibiting these cells could affect tumor progression.

scholarly journals Natural Killer Cell Responses in Hepatocellular Carcinoma: Implications for Novel Immunotherapeutic Approaches

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 926 ◽  
Author(s):  
Stefania Mantovani ◽  
Barbara Oliviero ◽  
Stefania Varchetta ◽  
Dalila Mele ◽  
Mario U. Mondelli
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Nk Cells ◽  
Natural Killer ◽  
Immune Escape ◽  
Nk Cell ◽  
Ex Vivo ◽  
Killer Cell ◽  
Current Status ◽  
Tumor Immune Escape

Hepatocellular carcinoma (HCC) still represents a significant complication of chronic liver disease, particularly when cirrhosis ensues. Current treatment options include surgery, loco-regional procedures and chemotherapy, according to specific clinical practice guidelines. Immunotherapy with check-point inhibitors, aimed at rescuing T-cells from exhaustion, has been applied as second-line therapy with limited and variable success. Natural killer (NK) cells are an essential component of innate immunity against cancer and changes in phenotype and function have been described in patients with HCC, who also show perturbations of NK activating receptor/ligand axes. Here we discuss the current status of NK cell treatment of HCC on the basis of existing evidence and ongoing clinical trials on adoptive transfer of autologous or allogeneic NK cells ex vivo or after activation with cytokines such as IL-15 and use of antibodies to target cell-expressed molecules to promote antibody-dependent cellular cytotoxicity (ADCC). To this end, bi-, tri- and tetra-specific killer cell engagers are being devised to improve NK cell recognition of tumor cells, circumventing tumor immune escape and efficiently targeting NK cells to tumors. Moreover, the exciting technique of chimeric antigen receptor (CAR)-engineered NK cells offers unique opportunities to create CAR-NK with multiple specificities along the experience gained with CAR-T cells with potentially less adverse effects.

CD8+ T Cells That Produce Interleukin-17 Regulate Myeloid-Derived Suppressor Cells and Are Associated With Survival Time of Patients With Gastric Cancer

2012 ◽  
Vol 143 (4) ◽  
pp. 951-962.e8 ◽  
Author(s):  
Yuan Zhuang ◽  
Liu–Sheng Peng ◽  
Yong–Liang Zhao ◽  
Yun Shi ◽  
Xu–Hu Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
T Cells ◽  
Survival Time ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Interleukin 17 ◽  
Myeloid Derived Suppressor Cells

Increased Population Of Myeloid-Derived Suppressor Cells In Patients With Myelodysplastic Syndromes Overexpress ARG1 and Mediate CD8+ T Cell Inhibition

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5212-5212 ◽  
Author(s):  
Zonghong Shao ◽  
Huijuan Jiang ◽  
Rong Fu
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Myelodysplastic Syndromes ◽  
Suppressor Cells ◽  
Cd8 T Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Normal Controls ◽  
Apoptosis Ratio

Abstract Objective To investigate the proportion and activation of myeloid- derived suppressor cells (MDSC) in bone marrow from patients with myelodysplastic syndromes (MDS). Methods The proportion of MDSC (Lin-HLA-DR-CD33+) in bone marrow of 30 MDS patients and 19 normal controls were measured by flow cytometry assay(FCM). MDSC and CD8+ T cell were isolated from bone marrow of 14 MDS patients and 14 normal controls among them by FCM and microbeads. The expressions of arginase 1(ARG1) and inducible nitric oxide synthase (iNOS) were analyzed by qPCR and western bolting. Co-cultures with CD8+ T cell were proved the MDSC-mediated inhibition of CD8+ T cell. Results MDS patient’s median MDSC were 7.29% which was higher than that of controls (2.91%). The expression of ARG1 and iNOS mRNA in MDSC of high-risk MDS patients was higher than that of low-risk MDS patients. But the protein of ARG1 was overexpressed rather than that of iNOS. After co-cultured, the apoptosis ratio of CD8+ T cells of MDS((64.17±4.86) %) was increased compared to pure CD8+ T cells ( (54.58±9.95)%). Further more, the production of IFN-γsecreted by CD8+ T cells co-cultured with MDSC ((551.94±47.39) pg/ml)was lower than that of pure CD8+ T cells ((586.04±46.65) pg/ml) There was no significant difference in level of TNF-βbetween co-cultured with MDSC and pure CD8+ cells. Conclusion The proportion of MDSC in bone marrow was increased significantly in MDS. MDSC overexpressed ARG1 in patients with MDS and correlated to the malignant degree of this disease. Further more, MDSC can increased the apoptosis ratio of CD8+ T cell, and inhibited the secretion of IFN-γ. These findings suggested MDSC mediated the response of immunosuppression in MDS. Disclosures: No relevant conflicts of interest to declare.

MMP-9-cleaved osteopontin isoform mediates tumor immune escape by inducing expansion of myeloid-derived suppressor cells

2017 ◽  
Vol 493 (4) ◽  
pp. 1478-1484 ◽  
Author(s):  
Lijuan Shao ◽  
Bo Zhang ◽  
Lingxiong Wang ◽  
Liangliang Wu ◽  
Quancheng Kan ◽  
...  
Keyword(s):  
Immune Escape ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape

scholarly journals The role of tumor-derived exosomes in tumor immune escape: A concise review

2020 ◽  
Vol 7 (11) ◽  
pp. 4132-4137
Author(s):  
Nhat Chau Truong ◽  
Thao Nhi Huynh ◽  
Khuong Duy Pham ◽  
Phuc Van Pham
Keyword(s):  
Immune Modulation ◽  
Immune Escape ◽  
Suppressor Cells ◽  
Target Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Immune Escape ◽  
Concise Review ◽  
Viable Cells ◽  
Immune Escape Mechanisms

Exosomes are small vesicles secreted by viable cells into the microenvironment. These vesicles bring various compositions, including lipids, RNAs and proteins, which carry information from producer cells to target cells. Cancer cells also produce exosomes, termed as tumor-derived exosomes (TDEs), which play important roles in immune modulation, angiogenesis and metastasis of tumors. This review summarizes the roles of TDEs in tumor immune escape mechanisms. TDEs affect all kinds of tumor-associated immune cells, including natural killer (NK) cells, dendritic cells (DCs), T and B lymphocytes, and myeloid-derived suppressor cells (MDSCs). Generally, TDEs suppress the immune system to promote tumor immune escape, thereby significantly contributing to tumorigenesis and metastasis.

scholarly journals Inhibition of Arginase 1 Liberates Potent T Cell Immunostimulatory Activity of Human Neutrophil Granulocytes

2021 ◽  
Vol 11 ◽  
Author(s):  
Verena Vonwirth ◽  
Yagmur Bülbül ◽  
Anke Werner ◽  
Hakim Echchannaoui ◽  
Johannes Windschmitt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Immune Escape ◽  
Suppressor Cells ◽  
T Cell Proliferation ◽  
Neutrophil Granulocytes ◽  
Tumor Immune Escape ◽  
Cell Functions ◽  
Arginase 1

Myeloid cell arginase-mediated arginine depletion with consecutive inhibition of T cell functions is a key component of tumor immune escape. Both, granulocytic myeloid-derived suppressor cells (G-MDSC) and conventional mature human polymorphonuclear neutrophil granulocytes (PMN) express high levels of arginase 1 and can act as suppressor cells of adaptive anti-cancer immunity. Here we demonstrate that pharmacological inhibition of PMN-derived arginase 1 not only prevents the suppression of T cell functions but rather leads to a strong hyperactivation of T cells. Human PMN were incubated in cell culture medium in the absence or presence of an arginase inhibitor. T cells from healthy donors were then activated either polyclonally or in an antigen-specific manner in the supernatants of the PMN cultures at different PMN-T cell ratios. T cell proliferation was completely suppressed in these supernatants in the absence of an arginase inhibitor. Arginase inhibition led to a strong hyperinduction of T cell proliferation, which exceeded control activation conditions up to 25-fold. The hyperinduction was correlated with higher PMN-T cell ratios and was only apparent when PMN arginase activity was blocked sufficiently. The T cell stimulatory factor was liberated very early by PMN and was present in the < 3 kDa fraction of the PMN supernatants. Increased T cell production of specific proinflammatory cytokines by PMN supernatant in the presence of arginase inhibitor was apparent. Upon arginase inhibition, downregulation of important T cell membrane activation and costimulation proteins was completely prevented or de novo induction accelerated. Antigen-specific T cell cytotoxicity against tumor cells was enhanced by PMN supernatant itself and could be further increased by PMN arginase blockade. Finally, we analyzed anergic T cells from multiple myeloma patients and noticed a complete reversal of anergy and the induction of strong proliferation upon T cell activation in PMN supernatants by arginase inhibition. In summary, we discovered a potent PMN-mediated hyperactivation of human T cells, which is apparent only when PMN arginase-mediated arginine depletion is concurrently inhibited. Our findings are clearly relevant for the analysis and prevention of human tumor immune escape in conjunction with the application of arginase inhibitors already being developed clinically.

scholarly journals Myeloid-Derived Suppressor Cells Down-Regulate L-Selectin Expression on CD4+ and CD8+ T Cells

2009 ◽  
Vol 183 (2) ◽  
pp. 937-944 ◽  
Author(s):  
Erica M. Hanson ◽  
Virginia K. Clements ◽  
Pratima Sinha ◽  
Dan Ilkovitch ◽  
Suzanne Ostrand-Rosenberg
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells
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