Tumor-associated nonmyelinating Schwann cell–expressed <i>PVT1</i> promotes pancreatic cancer kynurenine pathway and tumor immune exclusion-Reference-Cited by-同舟云学术

Tumor-associated nonmyelinating Schwann cell–expressed PVT1 promotes pancreatic cancer kynurenine pathway and tumor immune exclusion

Published:2023-02-03 Issue:5 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Sun Chengcao¹^ORCID,Ye Youqiong²^ORCID,Tan Zhi³^ORCID,Liu Yuan⁴^ORCID,Li Yajuan¹^ORCID,Hu Wei⁵,Liang Ke¹,Egranov Sergey D.¹,Huang Lisa Angela¹,Zhang Zhao²^ORCID,Zhang Yaohua¹^ORCID,Yao Jun¹^ORCID,Nguyen Tina K.¹,Zhao Zilong¹^ORCID,Wu Andrew¹^ORCID,Marks Jeffrey R.⁶^ORCID,Caudle Abigail S.⁷,Sahin Aysegul A.⁸,Gao Jianjun⁹^ORCID,Gammon Seth T.¹⁰^ORCID,Piwnica-Worms David¹⁰^ORCID,Hu Jian¹¹¹²^ORCID,Chiao Paul J.¹¹²,Yu Dihua¹¹²^ORCID,Hung Mien-Chie¹³¹⁴^ORCID,Curran Michael A.¹²¹⁵^ORCID,Calin George A.¹⁶¹⁷,Ying Haoqiang¹¹²^ORCID,Han Leng²⁴^ORCID,Lin Chunru¹¹²^ORCID,Yang Liuqing¹¹²¹⁷^ORCID

Affiliation:

1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

2. Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX 77030, USA.

3. Center for Drug Discovery, Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.

4. Center for Epigenetics and Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.

5. Institute of Translational Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201620, China.

6. Division of Surgical Science, Department of Surgery, Duke University, School of Medicine, Durham, NC 27710, USA.

7. Department of Breast Surgical Oncology, Division of Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

8. Department of Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

9. Department of Genitourinary Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

10. Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

11. Department of Cancer Biology, Division of Basic Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

12. The Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

13. Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology, and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan.

14. Department of Biotechnology, Asia University, Taichung 413, Taiwan.

15. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

16. Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

17. Center for RNA Interference and Non-Coding RNAs, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

Abstract

One of the major obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is its immunoresistant microenvironment. The functional importance and molecular mechanisms of Schwann cells in PDAC remains largely elusive. We characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc) in PDAC and indicated that the abundance of TASc was correlated with immune suppressive tumor microenvironment and the unfavorable outcome of patients with PDAC. Depletion of pancreatic-specific TASc promoted the tumorigenesis of PDAC tumors. TASc-expressed long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 ( PVT1 ) was triggered by the tumor cell–produced interleukin-6. Mechanistically, PVT1 modulated RAF proto-oncogene serine/threonine protein kinase–mediated phosphorylation of tryptophan 2,3-dioxygenase in TASc, facilitating its enzymatic activities in catalysis of tryptophan to kynurenine. Depletion of TASc-expressed PVT1 suppressed PDAC tumor growth. Furthermore, depletion of TASc using a small-molecule inhibitor effectively sensitized PDAC to immunotherapy, signifying the important roles of TASc in PDAC immune resistance.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.add6995

Reference65 articles.

1. Pancreatic cancer: why is it so hard to treat?

2. KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer

3. Current progress in immunotherapy for pancreatic cancer

4. Oncogenic KRAS-Driven Metabolic Reprogramming in Pancreatic Cancer Cells Utilizes Cytokines from the Tumor Microenvironment

5. Neural plasticity in pancreatitis and pancreatic cancer

Cited by 9 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Pancreatic Schwann cell reprogramming supports cancer-associated neuronal remodeling;2023-12-20

2. Cell-in-Cell–Mediated Entosis Reveals a Progressive Mechanism in Pancreatic Cancer;Gastroenterology;2023-12

3. The Expanding Roles of Long Non‐Coding RNAs in Pancreatic Cancer;Advanced Therapeutics;2023-09-29

4. Noncoding RNAs as an emerging resistance mechanism to immunotherapies in cancer: basic evidence and therapeutic implications;Frontiers in Immunology;2023-09-12

5. Glial cell-derived soluble factors increase the metastatic potential of pancreatic adenocarcinoma cells and induce epithelial-to-mesenchymal transition;Journal of Cancer Research and Clinical Oncology;2023-08-12