Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression

Wang, Guocan; Lü, Xin; Dey, Prasenjit; Deng, Pingna; Wu, Chia Chin; Jiang, Shan; Fang, Zhuangna; Zhao, Kun; Konaparthi, Ramakrishna; Hua, Sujun; Zhang, Jianhua; Li-Ning-Tapia, Elsa M.; Kapoor, Avnish; Wu, Chang Jiun; Patel, Neelay Bhaskar; Guo, Zhenglin; Ramamoorthy, Vandhana; Tieu, Trang N.; Heffernan, Timothy; Zhao, Di; Shang, Xiaoying; Khadka, Sunada; Hou, Pingping; Hu, Baoli; Jin, Eun Hyo; Yao, Wantong; Pan, Xiaolu; Ding, Zhihu; Shi, Yanxia; Li, Liren; Chang, Qing; Troncoso, Patricia; Logothetis, Christopher J.; McArthur, Mark J.; Chin, Lynda; Wang, Y. Alan; DePinho, Ronald A.

doi:10.1158/2159-8290.cd-15-0224

Cited by 439 publications

(448 citation statements)

References 41 publications

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“…Numerous reports describe the presence of MDSC in murine tumors (reviewed in [22, 23]) and recent studies demonstrated that tumor associated MDSC have an important role in tumor progression [24, 25]. In humans, recent studies described the presence of MDSC in glioblastoma [26], urothelial carcinoma [27], pancreatic adenocarcinoma [7], and breast cancer [28].…”

Section: Regulation Of Mdsc Recruitment To Tumorsmentioning

confidence: 99%

The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

Kumar

Patel

Tcyganov

et al. 2016

Trends in Immunology

1,638

1,458

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Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor microenvironment. The main feature of these cells is their potent immune suppressive activity. MDSC are generated in the bone marrow, and in tumor-bearing hosts, migrate to peripheral lymphoid organs and the tumor to contribute to the formation of the tumor microenvironment. Recent findings have revealed differences in the function and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings here, and in this context we discuss the current understanding as to the nature of these differences, the underlying mechanisms, and their potential impact on the regulation of tumor progression.

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Section: Regulation Of Mdsc Recruitment To Tumorsmentioning

confidence: 99%

The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

Kumar

Patel

Tcyganov

et al. 2016

Trends in Immunology

1,638

1,458

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show abstract

“…YAP has also been identified in human MPM and is correlated with tumorigenesis and cancer development, suggesting YAP is a therapeutic target for treating advanced unresectable MPM 19, 20, 21. YAP regulates tumour‐associated immune cells such as myeloid‐derived suppressor cells (MDSCs) and tumour‐associated macrophages (TAMs) 22, 23. YAP may be involved in the immune checkpoint 22, 23.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

Hsu

Miao

Wang

et al. 2018

J Cellular Molecular Medi

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Although tumour PD‐L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD‐L1 axis in various cancers, the regulation of PD‐L1 (CD274) expression is unclear. Yes‐associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down‐regulates PD‐L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD‐L1 protein expression compared to H290, MS‐1 and H28 cells. In H2052 and 211H cells, PD‐L1 mRNA expression was significantly increased compared to other MPM cell lines; YAP knockdown by small interfering RNA decreased PD‐L1 protein and mRNA expression. Forced overexpression of the YAP gene increased PD‐L1 protein expression in H2452 cells. Chromatin immunoprecipitation (ChIP) assay showed the precipitation of PD‐L1 enhancer region encompassing 2 putative YAP‐TEAD‐binding sites in H2052 cells. We found that, in human MPM tissue microarray samples, YAP and PD‐L1 concurrently expressed in immunohistochemistry stain (n = 70, P < .05, chi‐square). We conclude that PD‐L1 is correlated with YAP expression, and inhibition of YAP down‐regulates PD‐L1 expression in human MPM. Further study of how YAP regulates PD‐L1 in MPM is warranted.

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“…Almost all of the roles of YAP-1 have been identified from tumor cells; a little knowledge has been identified concerning its roles in the immune cell. However, several studies have revealed its role in immunosuppression [19,20], it is meaningful to investigate its role in Treg development in HCC.…”

Section: Introductionmentioning

confidence: 99%

YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

Fan¹,

Gao²,

Rao³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Immunosuppression is one of the hallmarks of cancer; however, its molecular mechanism remains unknown. In the present study, we sought to investigate the expression and activation of yes-associated protein 1 (YAP-1) and its roles in T cells within hepatocellular carcinoma (HCC). Methods: The expression and activation of YAP-1 were accessed by real-time PCR, immunohistochemistry staining, western blot, and flow cytometry. The potential regulation effect of YAP-1 on Regulatory T cells (Tregs) differentiation was predicted using bioinformatics tools and verified by in vitro studies. Results: Significant overexpression and activation of YAP-1 was detected within peripheral blood mononuclear cells and showed positive linear correlation to Treg percentage; it may serve as a valuable indicator of a bad prognosis. Using in vitro studies, we found that overexpression and activation of YAP-1 can promote naïve T cell polarization stimulation to Tregs by increasing the expression of TGFBR2. The YAP-1/TEADs DNA binding site was spotted within the promoter region of TGFBR2 and related to its transcription activity. YAP-1 acted as a co-activator of TGFBR2 transcription by binding directly to the TGFBR2 promoter through TEADs. Conclusion: Overexpression and activation of YAP-1 in HCC T cells can induce immunosuppression by promoting Treg differentiation via transcriptional enhancement of TGFBR2.

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Targeting YAP-Dependent MDSC Infiltration Impairs Tumor Progression

Cited by 439 publications

References 41 publications

The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment

Inhibition of yes‐associated protein down‐regulates PD‐L1 (CD274) expression in human malignant pleural mesothelioma

YAP-1 Promotes Tregs Differentiation in Hepatocellular Carcinoma by Enhancing TGFBR2 Transcription

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