What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment

International Journal of Molecular Sciences

Daniel M. Berney¹  Stefania Croci²  Martina Bonacini²  Carolina Castro Ruiz³  Jatin Gandhi⁴  Alessandra Soriano⁵  Sofia Cañete-Portillo⁶  Dario De Biase⁷  Alcides Chaux⁸  Giuseppe Carrieri⁹  Luigi Cormio⁹  Beatrice Melli^1,10  Guido Giordano^1,11  Matteo Landriscina^1,11  Antonio De Leo^1,12  Stefano Ascani^1,13  Moira Ragazzi^1,14  Giacomo Santandrea^1,14  Maria Paola Bonasoni^1,14  Giuditta Bernardelli^1,14  Eleonora Zanetti^1,14  Alessandra Bisagni^1,14  Magda Zanelli^1,14  Valerio Copelli^1,14  Andrea Palicelli^1,14  Francesca Sanguedolce^1,15  Maurizio Zizzo^1,16 

[1] Barts Cancer Institute, Queen Mary University of London, London EC1M 5PZ, UK;Clinical Immunology, Allergy and Advanced Biotechnologies Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy;Department of Pathology and Laboratory Medicine, University of Washington, Seattle, WA 98195, USA;Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA;Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA;Department of Pharmacy and Biotechnology (FABIT), University of Bologna, 40126 Bologna, Italy;Department of Scientific Research, School of Postgraduate Studies, Norte University, Asunción 1614, Paraguay;Department of Urology and Renal Transplantation, University of Foggia, 71122 Foggia, Italy;Fertility Centre, Department of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Medical Oncology Unit, Department of Medical and Surgical Sciences, University of Foggia, 71122 Foggia, Italy;Molecular Diagnostic Unit, Azienda USL Bologna, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy;Pathology Unit, Azienda Ospedaliera Santa Maria di Terni, University of Perugia, 05100 Terni, Italy;Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;Pathology Unit, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy;Surgical Oncology Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy;

关键词: PD-L1;    prostate;    cancer;    signaling pathways;    tumor microenvironment;    target-therapy;   

DOI  :  10.3390/ijms222212330

来源: DOAJ

【 摘 要 】

The tumor microenvironment (TME) includes immune (T, B, NK, dendritic), stromal, mesenchymal, endothelial, adipocytic cells, extracellular matrix, and cytokines/chemokines/soluble factors regulating various intracellular signaling pathways (ISP) in tumor cells. TME influences the survival/progression of prostate cancer (PC), enabling tumor cell immune-evasion also through the activation of the PD-1/PD-L1 axis. We have performed a systematic literature review according to the PRISMA guidelines, to investigate how the PD-1/PD-L1 pathway is influenced by TME and ISPs. Tumor immune-escape mechanisms include suppression/exhaustion of tumor infiltrating cytotoxic T lymphocytes, inhibition of tumor suppressive NK cells, increase in immune-suppressive immune cells (regulatory T, M2 macrophagic, myeloid-derived suppressor, dendritic, stromal, and adipocytic cells). IFN-γ (the most investigated factor), TGF-β, TNF-α, IL-6, IL-17, IL-15, IL-27, complement factor C5a, and other soluble molecules secreted by TME components (and sometimes increased in patients’ serum), as well as and hypoxia, influenced the regulation of PD-L1. Experimental studies using human and mouse PC cell lines (derived from either androgen-sensitive or androgen-resistant tumors) revealed that the intracellular ERK/MEK, Akt-mTOR, NF-kB, WNT and JAK/STAT pathways were involved in PD-L1 upregulation in PC. Blocking the PD-1/PD-L1 signaling by using immunotherapy drugs can prevent tumor immune-escape, increasing the anti-tumor activity of immune cells.

【 授权许可】

Unknown