IL‐33 inhibits the differentiation and immunosuppressive activity of granulocytic myeloid‐derived suppressor cells in tumor‐bearing mice

2016 ◽  
Vol 95 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Hui Xuan Lim ◽  
Seulah Choi ◽  
Daeho Cho ◽  
Tae Sung Kim
Keyword(s):  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Activity ◽  
Tumor Bearing

scholarly journals Metformin inhibits the function of granulocytic myeloid-derived suppressor cells in tumor-bearing mice

2019 ◽  
Vol 120 ◽  
pp. 109458 ◽  
Author(s):  
Peiqi Xu ◽  
Kai Yin ◽  
Xinyi Tang ◽  
Jie Tian ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing

scholarly journals Human Isogenic Cell Line Models for Neutrophils and Myeloid-Derived Suppressor Cells

2020 ◽  
Vol 21 (20) ◽  
pp. 7709
Author(s):  
Yuting Zhang ◽  
Emily Wilt ◽  
Xin Lu
Keyword(s):  
Cell Line ◽  
Suppressor Cells ◽  
Jurkat Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Activity ◽  
Line System ◽  
Gm Csf ◽  
Activation Induced Cell Death ◽  
Isogenic Cell Line ◽  
Human T Cell

Neutrophils with immunosuppressive activity are polymorphonuclear myeloid-derived suppressor cells (MDSCs) and may contribute to the resistance to cancer immunotherapy. A major gap for understanding and targeting these cells is the paucity of cell line models with cardinal features of human immunosuppressive neutrophils and their normal counterparts, especially in an isogenic manner. To address this issue, we employ the human promyelocytic cell line HL60 and use DMSO and cytokines (granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin 6 (IL6)) to induce the formation of either neutrophils or MDSCs. The induced MDSCs are CD11b+ CD33+ HLA-DR−/low and are heterogeneous for CD15 and CD14 expression. The induced MDSCs abrogate IL2 production and activation-induced cell death of the human T cell line Jurkat stimulated by CD3/CD28 antibodies, whereas the induced neutrophils enhance IL2 production from Jurkat cells. The induced MDSCs upregulate the expression of C/EBPβ, STAT3, VEGFR1, FATP2 and S100A8. Lastly, the immunosuppressive activity of the induced MDSCs is inhibited by all-trans retinoic acid and STAT3 inhibitor BP-1-102 through cellular differentiation and dedifferentiation mechanisms, respectively. Together, our study establishes a human isogenic cell line system for neutrophils and MDSCs and this system is expected to facilitate future studies on the biology and therapeutics of human immunosuppressive neutrophils.

scholarly journals Anti-Gr-1 antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice

2012 ◽  
Vol 92 (6) ◽  
pp. 1199-1206 ◽  
Author(s):  
Chi Ma ◽  
Tamar Kapanadze ◽  
Jaba Gamrekelashvili ◽  
Michael P. Manns ◽  
Firouzeh Korangy ◽  
...  
Keyword(s):  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing

scholarly journals Independent mechanisms of T cell-suppression by subpopulations of myeloid-derived suppressor cells (MDSC) in tumor-bearing hosts

2013 ◽  
Vol 1 (Suppl 1) ◽  
pp. P193
Author(s):  
Patrick L Raber ◽  
Paul Thevenot ◽  
Rosa Sierra ◽  
Dorota Wyczechowska ◽  
Maria E Ramirez ◽  
...  
Keyword(s):  
T Cell ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Bearing ◽  
T Cell Suppression ◽  
Cell Suppression

Development of myeloid-derived suppressor cells (MDSC) targeted therapy for the treatment of cisplatin-resistant bladder cancer.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 415-415
Author(s):  
Yuji Takeyama ◽  
Minoru Kato ◽  
Yasuomi Shimizu ◽  
Kosuke Hamada ◽  
Taro Iguchi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Suppressor Cells ◽  
Bladder Cancer Cell ◽  
Myeloid Derived Suppressor Cells ◽  
Expression Levels ◽  
Tumor Bearing ◽  
Gene Expression Levels

415 Background: The emergence of immune checkpoint inhibitors (ICI) has brought hope for cure and survival for those suffering from various cancers, including bladder cancer. However, the response rate of ICI monotherapy is modest, and recent reports indicate that myeloid-derived suppressor cells (MDSC) might play a role in the resistant mechanism of ICI. In this study, we assess the effect of chemokine signal on the proliferation of bladder cancer and investigate whether MDSC could be a new target for the treatment of cisplatin-resistant bladder cancer. Methods: We established a cisplatin resistant strain (MB49R) of mice bladder cancer cell line MB49, and examined the alteration of the expression levels of inflammatory chemokines by chemokine array. Next, we isolated MDSCs from spleen and tumor in tumor-bearing mice to examine gene expression levels of chemokine receptors (CXCR2 and CCR2) and immunosuppression genes (Arg-1 and iNOS). Furthermore, we assessed the efficacy of CDDP, α-PD-L1 and chemokine antagonists against the proliferation of tumors in MB49 and MB49R xenograft models. Results: Expression levels of CCL2 and CXCL1/2, which are involved in the migration of MDSC, were significantly increased in the culture supernatant of MB49R compared to those in MB49 cell lines. This result was confirmed by real-time RT-qPCR of tumor extract, and this increase was also observed in human bladder cancer cell lines (T24 and T24R). CXCR2 and CCR2 were highly expressed in PMN-MDSC and M-MDSC, respectively, which were isolated from spleen or tumors in tumor-bearing mice, and gene expression levels of Arg-1 and iNOS were dramatically increased in M-MDSCs from the tumor tissues compared to those from spleen. Also, analysis by flow cytometry revealed that PMN-MDSC dramatically decreased in MB49R compared to parental MB49 tumors, while the proportion of M-MDSC was not changed in MB49R, which indicates that M-MDSC could be a target for the treatment of CDDP resistant bladder cancer. Conclusions: The results in the present study might indicate that the combination treatment with ICI and MDSC-targeting therapy could be an option for the treatment of cisplatin-resistant bladder cancer.

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