Bladder cancer cells induce immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through interleukin 10 - PubMed

Affiliations

• PMID: 27987237
• DOI: 10.1002/cbin.10716

Bladder cancer cells induce immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through interleukin 10

Xingyuan Wang et al. Cell Biol Int. 2017 Feb.

Abstract

Immunotherapy based on BCG vaccination is an effective treatment in bladder cancer, but a positive response is restricted to a subset of patients and for a limited period of time only. This suggests that T cells antitumour responses are effective but can become compromised in bladder cancer. To investigate the underlying mechanisms, we first identified peripheral blood monocytes and tumour macrophages using the pan-monocyte/macrophage marker CD14, and found that the PD-L1 expression on the monocytes/macrophages in bladder cancer patients was significantly higher than that in controls. The monocytes from bladder cancer patients were also more capable at inducing apoptosis and inhibiting proliferation in activated autologous T cells than monocytes from controls, which was directly associated with the level of PD-L1 expression. We next investigated the tumour cells' participation in upregulating PD-L1 in monocytes/macrophages. Significant elevation of PD-L1 was observed in monocytes after culturing with autologous tumour cells, which did not require direct contact but required soluble factors. The STAT phosphorylation pattern in monocytes after tumour cell co-culture was consistent with effects of the interleukin (IL)-10 signalling pathway. We then found that removal of IL-10 in monocyte-tumour cell co-culture reduced the PD-L1 upregulation in monocytes, but IL-10 by itself was unable to directly upregulate PD-L1. Primary bladder tumour cells secreted significant levels of IL-10, indicating that they could serve as the source of IL-10. Together, these results demonstrated a novel pathway that bladder cancer cells induced immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through IL-10.

Keywords: IL-10; PD-L1; bladder cancer; macrophage.

Similar articles

• PD-L1 expression on tolerogenic APCs is controlled by STAT-3.

  Wölfle SJ, Strebovsky J, Bartz H, Sähr A, Arnold C, Kaiser C, Dalpke AH, Heeg K. Wölfle SJ, et al. Eur J Immunol. 2011 Feb;41(2):413-24. doi: 10.1002/eji.201040979. Epub 2011 Jan 11. Eur J Immunol. 2011. PMID: 21268011

• Different roles of PD-L1 and FasL in immunomodulation mediated by human placenta-derived mesenchymal stem cells.

  Gu YZ, Xue Q, Chen YJ, Yu GH, Qing MD, Shen Y, Wang MY, Shi Q, Zhang XG. Gu YZ, et al. Hum Immunol. 2013 Mar;74(3):267-76. doi: 10.1016/j.humimm.2012.12.011. Epub 2012 Dec 20. Hum Immunol. 2013. PMID: 23261407

• Oral squamous cell carcinoma suppressed antitumor immunity through induction of PD-L1 expression on tumor-associated macrophages.

  Jiang C, Yuan F, Wang J, Wu L. Jiang C, et al. Immunobiology. 2017 Apr;222(4):651-657. doi: 10.1016/j.imbio.2016.12.002. Epub 2016 Dec 14. Immunobiology. 2017. PMID: 28017495

• Intrinsic and extrinsic control of expression of the immunoregulatory molecule PD-L1 in epithelial cells and squamous cell carcinoma.

  Ritprajak P, Azuma M. Ritprajak P, et al. Oral Oncol. 2015 Mar;51(3):221-8. doi: 10.1016/j.oraloncology.2014.11.014. Epub 2014 Dec 12. Oral Oncol. 2015. PMID: 25500094 Review.

• The PD-1/PD-L1 axis in the pathogenesis of urothelial bladder cancer and evaluating its potential as a therapeutic target.

  Bardoli AD, Afshar M, Viney R, Foster M, Porfiri E, Zarkar A, Stevenson R, James ND, Bryan RT, Patel P. Bardoli AD, et al. Future Oncol. 2016 Mar;12(5):595-600. doi: 10.2217/fon.15.337. Epub 2016 Feb 1. Future Oncol. 2016. PMID: 26880382 Review. No abstract available.

Cited by

• Regulation of PD-L1 Expression by NF-κB in Cancer.

  Antonangeli F, Natalini A, Garassino MC, Sica A, Santoni A, Di Rosa F. Antonangeli F, et al. Front Immunol. 2020 Nov 25;11:584626. doi: 10.3389/fimmu.2020.584626. eCollection 2020. Front Immunol. 2020. PMID: 33324403 Free PMC article. Review.

• NDRG2 Expression in Breast Cancer Cells Downregulates PD-L1 Expression and Restores T Cell Proliferation in Tumor-Coculture.

  Lee A, Lim S, Oh J, Lim J, Yang Y, Lee MS, Lim JS. Lee A, et al. Cancers (Basel). 2021 Dec 4;13(23):6112. doi: 10.3390/cancers13236112. Cancers (Basel). 2021. PMID: 34885221 Free PMC article.

• Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape.

  Jiang X, Wang J, Deng X, Xiong F, Ge J, Xiang B, Wu X, Ma J, Zhou M, Li X, Li Y, Li G, Xiong W, Guo C, Zeng Z. Jiang X, et al. Mol Cancer. 2019 Jan 15;18(1):10. doi: 10.1186/s12943-018-0928-4. Mol Cancer. 2019. PMID: 30646912 Free PMC article. Review.

• Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer.

  Chen X, Jin Y, Gong L, He D, Cheng Y, Xiao M, Zhu Y, Wang Z, Cao K. Chen X, et al. Front Genet. 2020 Jun 23;11:607. doi: 10.3389/fgene.2020.00607. eCollection 2020. Front Genet. 2020. PMID: 32655621 Free PMC article.

• Tumor-Associated Macrophages in Bladder Cancer: Biological Role, Impact on Therapeutic Response and Perspectives for Immunotherapy.

  Leblond MM, Zdimerova H, Desponds E, Verdeil G. Leblond MM, et al. Cancers (Basel). 2021 Sep 21;13(18):4712. doi: 10.3390/cancers13184712. Cancers (Basel). 2021. PMID: 34572939 Free PMC article. Review.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Wiley

• Other Literature Sources

  • scite Smart Citations

• Research Materials

  • NCI CPTC Antibody Characterization Program