Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January-2018 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2018 Volume 15 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer

  • Authors:
    • Jinhong Wang
    • Li Zhang
    • Dong Kang
    • Deguang Yang
    • Ying Tang
  • View Affiliations / Copyright

    Affiliations: Respiratory Department, The Third Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Huiqiao Department, South Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, Department of Cardiology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China, Department of Respiration, The First Hospital, Jilin University, Changchun, Jilin 130000, P.R. China
  • Pages: 552-558
    |
    Published online on: October 26, 2017
       https://doi.org/10.3892/ol.2017.7279
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed to identify the level of programmed death‑1 (PD‑1) expression in infiltrating cluster of differentiation (CD)4+ and CD8+ T cells isolated from lung cancer tissues, and investigated whether the level of PD‑1 expression may be directly regulated by lung cancer cells via prostaglandin E2 (PGE2)‑associated signaling pathways in patients with lung cancer. A total of 75 patients with lung cancer were enrolled in the present study. The percentage of infiltrating CD4+ and CD8+ T cells was determined by flow cytometry. ELISA was performed to evaluate the concentration of PGE2 in lung cancer tissue homogenate. The correlation between PGE2 and PD‑1 expression levels in CD8+ T cells was assessed by Spearman's rank correlation test. The expression levels of PD‑1 and PGE2 receptors were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively. The level of PD‑1 expression in infiltrating CD8+ T cells was gradually increased as the stage of lung cancer increased. The level of PD‑1 expression was also positively associated with the concentration of PGE2 in lung cancer tissues. Furthermore, the level of PD‑1 expression was closely associated with the PGE2/EP2 and PGE2/EP4 signaling pathways. The activation of PGE2‑associated EP2‑ and EP4‑pathways may positively regulate the level of PD‑1 in infiltrating CD8+ T cells, which results in immune tolerance in the lung cancer microenvironment.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Sun S, Schiller JH, Spinola M and Minna JD: New molecularly targeted therapies for lung cancer. J Clin Invest. 117:2740–2750. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Rolfo C, Sortino G, Smits E, Passiglia F, Bronte G, Castiglia M, Russo A, Santos ES, Janssens A, Pauwels P and Raez L: Immunotherapy: Is a minor god yet in the pantheon of treatments for lung cancer? Expert Rev Anticancer Ther. 14:1173–1187. 2014. View Article : Google Scholar : PubMed/NCBI

4 

Fazilleau N, Mark L, McHeyzer-Willams LJ and McHeyzer-Williams MG: Follicular helper T cells: Lineage and location. Immunity. 30:324–335. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Inoue S, Leitner WW, Golding B and Scott D: Inhibitory effects of B cells on antitumor immunity. Cancer Res. 66:7741–7747. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Lee-Chang C, Bodogai M, Martin-Montalvo A, Wejksza K, Sanghvi M, Moaddel R, de Cabo R and Biragyn A: Inhibition of breast cancer metastasis by resveratrol-mediated inactivation of tumor-evoked regulatory B cells. J Immunol. 191:4141–4151. 2013. View Article : Google Scholar : PubMed/NCBI

7 

O'Callaghan G and Houston A: Prostaglandin E2 and the EP receptors in malignancy: Possible therapeutic targets? Br J Pharmacol. 172:5239–5250. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Pai R, Soreghan B, Szabo IL, Pavelka M, Baatar D and Tarnawski AS: Prostaglandin E2 transactivates EGF receptor: A novel mechanism for promoting colon cancer growth and gastrointestinal hypertrophy. Nat Med. 8:289–293. 2002. View Article : Google Scholar : PubMed/NCBI

9 

Baratelli F, Lin Y, Zhu L, Yang SC, Heuzé-Vourc'h N, Zeng G, Reckamp K, Dohadwala M, Sharma S and Dubinett SM: Prostaglandin E2 induces FOXP3 gene expression and T regulatory cell function in human CD4+ T cells. J Immunol. 175:1483–1490. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Chemnitz JM, Parry RV, Nichols KE, June CH and Riley JL: SHP-1 and SHP-2 associate with immunoreceptor tyrosine-based switch motif of programmed death 1 upon primary human T cell stimulation, but only receptor ligation prevents T cell activation. J Immunol. 173:945–954. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Park JJ, Omiya R, Matsumura Y, Sakoda Y, Kuramasu A, Augustine MM, Yao S, Tsushima F, Narazaki H, Anand S, et al: B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood. 116:1291–1298. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu J, Zhu G, Tamada K, et al: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat Med. 8:793–800. 2002. View Article : Google Scholar : PubMed/NCBI

13 

Chen JH, Perry CJ, Tsui YC, Staron MM, Parish IA, Dominguez CX, Rosenberg DW and Kaech SM: Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection. Nat Med. 21:327–334. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Rami-Porta R, Bolejack V, Giroux DJ, Chansky K, Crowley J, Asamura H and Goldstraw P; International Association for the Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Board Members and Participating Institutions, : The IASLC lung cancer staging project: The new database to inform the eighth edition of the TNM classification of lung cancer. J Thorac Oncol. 9:1618–1624. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

16 

Garnelo M, Tan A, Her Z, Yeong J, Lim CJ, Chen J, Lim KH, Weber A, Chow P, Chung A, et al: Interaction between tumour-infiltrating B cells and T cells controls the progression of hepatocellular carcinoma. Gut. 66:342–351. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Pagès F, Galon J, Dieu-Nosjean MC, Tartour E, Sautès-Fridman C and Fridman WH: Immune infiltration in human tumors: A prognostic factor that should not be ignored. Oncogene. 29:1093–1102. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Lin Z, Chen X, Li Z, Luo Y, Fang Z, Xu B and Han M: PD-1 antibody monotherapy for malignant melanoma: A systematic review and meta-analysis. PLoS One. 11:e01604852016. View Article : Google Scholar : PubMed/NCBI

19 

Wang X, Bao Z, Zhang X, Li F, Lai T, Cao C, Chen Z, Li W, Shen H and Ying S: Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: A systematic review and meta-analysis. Oncotarget. 8:59901–59914. 2017.PubMed/NCBI

20 

Yang L, Yamagata N, Yadav R, Brandon S, Courtney RL, Morrow JD, Shyr Y, Boothby M, Joyce S, Carbone DP and Breyer RM: Cancer-associated immunodeficiency and dendritic cell abnormalities mediated by the prostaglandin EP2 receptor. J Clin Invest. 111:727–735. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Nataraj C, Thomas DW, Tilley SL, Nguyen MT, Mannon R, Koller BH and Coffman TM: Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse. J Clin Invest. 108:1229–1235. 2001. View Article : Google Scholar : PubMed/NCBI

22 

von der Emde L, Goltz D, Latz S, Müller SC, Kristiansen G, Ellinger J and Syring I: Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer. Am J Cancer Res. 4:952–962. 2014.PubMed/NCBI

23 

Han L, Liu F, Li R, Li Z, Chen X, Zhou Z, Zhang X, Hu T, Zhang Y, Young K, et al: Role of programmed death ligands in effective T-cell interactions in extranodal natural killer/T-cell lymphoma. Oncol Lett. 8:1461–1469. 2014.PubMed/NCBI

24 

Zitvogel L and Kroemer G: Targeting PD-1/PD-L1 interactions for cancer immunotherapy. Oncoimmunology. 1:1223–1225. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Sakaguchi S, Vignali DA, Rudensky AY, Niec RE and Waldmann H: The plasticity and stability of regulatory T cells. Nat Rev Immunol. 13:461–467. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Yun X, Shang Y and Li M: Effect of Lactobacillus salivarius on Th1/Th2 cytokines and the number of spleen CD4+ CD25+ Foxp3+ Treg in asthma Balb/c mouse. Int J Clin Exp Pathol. 8:7661–7674. 2015.PubMed/NCBI

27 

Che D, Zhang S, Jing Z, Shang L, Jin S, Liu F, Shen J, Li Y, Hu J, Meng Q, et al: Macrophages induce EMT to promote invasion of lung cancer cells through the IL-6-mediated COX-2/PGE2/β-catenin signalling pathway. Mol Immunol. 90:197–210. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Fan Y, Wang Y and Wang K: Prostaglandin E2 stimulates normal bronchial epithelial cell growth through induction of c-Jun and PDK1, a kinase implicated in oncogenesis. Respir Res. 16:1492015. View Article : Google Scholar : PubMed/NCBI

29 

Quan Y, Jiang J and Dingledine R: EP2 receptor signaling pathways regulate classical activation of microglia. J Biol Chem. 288:9293–9302. 2013. View Article : Google Scholar : PubMed/NCBI

30 

Cho JS, Han IH, Lee HR and Lee HM: Prostaglandin E2 Induces IL-6 and IL-8 Production by the EP Receptors/Akt/NF-κB pathways in nasal polyp-derived fibroblasts. Allergy Asthma Immunol Res. 6:449–457. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Kim JI, Lakshmikanthan V, Frilot N and Daaka Y: Prostaglandin E2 promotes lung cancer cell migration via EP4-betaArrestin1-c-Src signalsome. Mol Cancer Res. 8:569–577. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Israel DD and Regan JW: EP(3) prostanoid receptor isoforms utilize distinct mechanisms to regulate ERK 1/2 activation. Biochim Biophys Acta. 1791:238–245. 2009. View Article : Google Scholar : PubMed/NCBI

33 

Amano H, Hayashi I, Endo H, Kitasato H, Yamashina S, Maruyama T, Kobayashi M, Satoh K, Narita M, Sugimoto Y, et al: Host prostaglandin E(2)-EP3 signaling regulates tumor-associated angiogenesis and tumor growth. J Exp Med. 197:221–232. 2003. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang J, Zhang L, Kang D, Yang D and Tang Y: Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer. Oncol Lett 15: 552-558, 2018.
APA
Wang, J., Zhang, L., Kang, D., Yang, D., & Tang, Y. (2018). Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer. Oncology Letters, 15, 552-558. https://doi.org/10.3892/ol.2017.7279
MLA
Wang, J., Zhang, L., Kang, D., Yang, D., Tang, Y."Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer". Oncology Letters 15.1 (2018): 552-558.
Chicago
Wang, J., Zhang, L., Kang, D., Yang, D., Tang, Y."Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer". Oncology Letters 15, no. 1 (2018): 552-558. https://doi.org/10.3892/ol.2017.7279
Copy and paste a formatted citation
x
Spandidos Publications style
Wang J, Zhang L, Kang D, Yang D and Tang Y: Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer. Oncol Lett 15: 552-558, 2018.
APA
Wang, J., Zhang, L., Kang, D., Yang, D., & Tang, Y. (2018). Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer. Oncology Letters, 15, 552-558. https://doi.org/10.3892/ol.2017.7279
MLA
Wang, J., Zhang, L., Kang, D., Yang, D., Tang, Y."Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer". Oncology Letters 15.1 (2018): 552-558.
Chicago
Wang, J., Zhang, L., Kang, D., Yang, D., Tang, Y."Activation of PGE2/EP2 and PGE2/EP4 signaling pathways positively regulate the level of PD‑1 in infiltrating CD8+ T cells in patients with lung cancer". Oncology Letters 15, no. 1 (2018): 552-558. https://doi.org/10.3892/ol.2017.7279
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team