Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer
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Cellular and Molecular Life Sciences
REVIEW
Clinical application of immune checkpoints in targeted immunotherapy of prostate cancer Sevda Jafari1,2 · Ommoleila Molavi1,2,3 · Houman Kahroba3,4 · Mohammad Saied Hejazi2,3 · Nasrin Maleki‑Dizaji5 · Siamak Barghi6 · Seyed Hossein Kiaie7,8 · Farhad Jadidi‑Niaragh9,10 Received: 17 July 2019 / Revised: 27 December 2019 / Accepted: 10 January 2020 © Springer Nature Switzerland AG 2020
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. Keywords Monoclonal antibody · Co-stimulatory · Co-inhibitory · Biomarkers · Clinical trials
Introduction Prostate cancer (PCa) is the most prevalent cancer among men and the second leading cause of cancer-related death in men worldwide. PCa-related mortality is estimated at 385,560 global deaths in 2020. Currently, approximately * Ommoleila Molavi [email protected] 1
Biotechnology Research Center, Tabriz University of Medical Science, Tabriz, Iran
2
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
3
Molecular Medicine Research Center, Biomedicine Institute, Tabriz University of Medical Science, Tabriz, Iran
4
Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
5
Department of Pharmacology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
50% of PCa patients are diagnosed with metastatic disease, and those with localized tumor show fairly rapid progression-to-advanced stages of the disease characterized by metastasis to long distant organs [1]. The relatively high incidence of PCa in men and its poor prognosis mark this deadly disease as
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