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Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer

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Abstract

Immunotherapy is considered as an effective method for cancer treatment owing to the induction of specific and long-lasting anti-cancer effects. Immunotherapeutic strategies have shown significant success in human malignancies, particularly in prostate cancer (PCa), a major global health issue regarding its high metastatic rates. In fact, the first cancer vaccine approved by FDA was Provenge, which has been successfully used for treatment of PCa. Despite the remarkable success of cancer immunotherapy in PCa, many of the developed immunotherapy methods show poor therapeutic outcomes. Immunosuppression in tumor microenvironment (TME) induced by non-functional T cells (CD4+ and CD8+), tolerogenic dendritic cells (DCs), and regulatory T cells, has been reported to be the main obstacle to the effectiveness of anti-tumor immune responses induced by an immunotherapy method. The present review particularly focuses on the latest findings of the immune checkpoints (ICPs), including CTLA-4, PD-1, PD-L1, LAG-3, OX40, B7-H3, 4-1BB, VISTA, TIM-3, and ICOS; these checkpoints are able to have immune modulatory effects on the TME of PCa. This paper further discusses different approaches in ICPs targeting therapy and summarizes the latest advances in the clinical application of ICP-targeted therapy as monotherapy or in combination with other cancer therapy modalities in PCa.

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Acknowledgements

This work is part of a dissertation (No. 128) by S. Jafari, submitted for Ph.D. degree and supported by Biotechnology Research Center, Tabriz University of Medical Sciences.

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Authors and Affiliations

  1. Biotechnology Research Center, Tabriz University of Medical Science, Tabriz, Iran

    Sevda Jafari & Ommoleila Molavi

  2. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Sevda Jafari, Ommoleila Molavi & Mohammad Saied Hejazi

  3. Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Science, Tabriz, Iran

    Ommoleila Molavi, Houman Kahroba & Mohammad Saied Hejazi

  4. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Houman Kahroba

  5. Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Nasrin Maleki-Dizaji

  6. Department of Medical Laboratory Sciences, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Science, Tehran, Iran

    Siamak Barghi

  7. Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

    Seyed Hossein Kiaie

  8. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Seyed Hossein Kiaie

  9. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Farhad Jadidi-Niaragh

  10. Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Farhad Jadidi-Niaragh

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  1. Sevda Jafari
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Correspondence to Ommoleila Molavi.

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Jafari, S., Molavi, O., Kahroba, H. et al. Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer. Cell. Mol. Life Sci. 77, 3693–3710 (2020). https://doi.org/10.1007/s00018-020-03459-1

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