For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
33
views
109
references
 Top references
cited by
53
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      335
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases worldwide. It is refractory to conventional treatments, and consequently has a documented 5-year survival rate as low as 7%. Increasing evidence indicates that activated pancreatic stellate cells (PSCs), one of the stromal components in tumor microenvironment (TME), play a crucial part in the desmoplasia, carcinogenesis, aggressiveness, metastasis associated with PDAC. Despite the current understanding of PSCs as a “partner in crime” to PDAC, detailed regulatory roles of PSCs and related microenvironment remain obscure. In addition to multiple paracrine signaling pathways, recent research has confirmed that PSCs-mediated tumor microenvironment may influence behaviors of PDAC via diverse mechanisms, such as rewiring metabolic networks, suppressing immune responses. These new activities are closely linked with treatment and prognosis of PDAC. In this review, we discuss the recent advances regarding new functions of activated PSCs, including PSCs-cancer cells interaction, mechanisms involved in immunosuppressive regulation, and metabolic reprogramming. It’s clear that these updated experimental or clinical studies of PSCs may provide a promising approach for PDAC treatment in the near future.

          Related collections

          Most cited references109

          • Record: found
          • Abstract: found
          • Article: not found

          LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells.

          Almut Brand, Katrin Singer, Gudrun Koehl … (2016)
          Elevated lactate dehydrogenase A (LDHA) expression is associated with poor outcome in tumor patients. Here we show that LDHA-associated lactic acid accumulation in melanomas inhibits tumor surveillance by T and NK cells. In immunocompetent C57BL/6 mice, tumors with reduced lactic acid production (Ldha(low)) developed significantly slower than control tumors and showed increased infiltration with IFN-γ-producing T and NK cells. However, in Rag2(-/-)γc(-/-) mice, lacking lymphocytes and NK cells, and in Ifng(-/-) mice, Ldha(low) and control cells formed tumors at similar rates. Pathophysiological concentrations of lactic acid prevented upregulation of nuclear factor of activated T cells (NFAT) in T and NK cells, resulting in diminished IFN-γ production. Database analyses revealed negative correlations between LDHA expression and T cell activation markers in human melanoma patients. Our results demonstrate that lactic acid is a potent inhibitor of function and survival of T and NK cells leading to tumor immune escape.
          Article 0 comments Cited 668 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.

            Mara Sherman, Ruth T Yu, Dannielle D. Engle … (2014)
            The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK: Copyright © 2014 Elsevier Inc. All rights reserved.
            Article 0 comments Cited 418 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies.

              Kristin G Anderson, Ingunn Stromnes, Philip D. Greenberg (2017)
              T cell dysfunction in solid tumors results from multiple mechanisms. Altered signaling pathways in tumor cells help produce a suppressive tumor microenvironment enriched for inhibitory cells, posing a major obstacle for cancer immunity. Metabolic constraints to cell function and survival shape tumor progression and immune cell function. In the face of persistent antigen, chronic T cell receptor signaling drives T lymphocytes to a functionally exhausted state. Here we discuss how the tumor and its microenvironment influences T cell trafficking and function with a focus on melanoma, and pancreatic and ovarian cancer, and discuss how scientific advances may help overcome these hurdles.
              Article 0 comments Cited 287 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                Hong Shen: 86-13574846576 , hongshen2000@csu.edu.cn
                Journal
                Journal ID (nlm-ta): Mol Cancer
                Journal ID (iso-abbrev): Mol. Cancer
                Title: Molecular Cancer
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1476-4598
                Publication date (Electronic): 19 February 2018
                Publication date PMC-release: 19 February 2018
                Publication date Collection: 2018
                Volume: 17
                Electronic Location Identifier: 62
                Affiliations
                [1 ]ISNI 0000 0004 1757 7615, GRID grid.452223.0, Department of Oncology, , Xiangya Hospital, Central South University, ; Changsha, Hunan 410008 China
                [2 ]Institute of Medical Sciences, Xiangya Hospital, Central South University, Changsha, Hunan 410008 China
                [3 ]ISNI 0000 0004 1757 7615, GRID grid.452223.0, Key Laboratory for Molecular Radiation Oncology of Hunan Province, , Xiangya Hospital, Central South University, ; Changsha, Hunan 410008 China
                Article
                Publisher ID: 815
                DOI: 10.1186/s12943-018-0815-z
                PMC ID: 5817854
                PubMed ID: 29458370
                SO-VID: bf840e11-ca22-4915-8d75-6bf6898c5b18
                Copyright © © The Author(s). 2018
                License:

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                Date received : 28 November 2017
                Date accepted : 12 February 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81172470
                Award ID: 81070362
                Award ID: 81372629
                Award ID: 81772627
                Award Recipient :
                Funded by: Nature Science Foundation of Hunan Province
                Award ID: 2015JC3021
                Award ID: 2016JC2037
                Award Recipient :
                Categories
                Subject: Review
                Custom metadata
                issue-copyright-statement © The Author(s) 2018

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic stellate cells,pdac,metabolic reprogramming,immune evasion,drug resistance
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: pancreatic stellate cells, pdac, metabolic reprogramming, immune evasion, drug resistance

                Comments

                Comment on this article

                scite_

                Similar content335

                See all similar

                Cited by53

                See all cited by

                Most referenced authors2,315

                See all reference authors