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- Title
What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).
- Authors
Palicelli, Andrea; Croci, Stefania; Bisagni, Alessandra; Zanetti, Eleonora; De Biase, Dario; Melli, Beatrice; Sanguedolce, Francesca; Ragazzi, Moira; Zanelli, Magda; Chaux, Alcides; Cañete-Portillo, Sofia; Bonasoni, Maria Paola; Soriano, Alessandra; Ascani, Stefano; Zizzo, Maurizio; Castro Ruiz, Carolina; De Leo, Antonio; Giordano, Guido; Landriscina, Matteo; Carrieri, Giuseppe
- Abstract
In prostate cancer (PC), the PD-1/PD-L1 axis regulates various signaling pathways and it is influenced by extracellular factors. Pre-clinical experimental studies investigating the effects of various treatments (alone or combined) may discover how to overcome the immunotherapy-resistance in PC-patients. We performed a systematic literature review (PRISMA guidelines) to delineate the landscape of pre-clinical studies (including cell lines and mouse models) that tested treatments with effects on PD-L1 signaling in PC. NF-kB, MEK, JAK, or STAT inhibitors on human/mouse, primary/metastatic PC-cell lines variably down-modulated PD-L1-expression, reducing chemoresistance and tumor cell migration. If PC-cells were co-cultured with NK, CD8+ T-cells or CAR-T cells, the immune cell cytotoxicity increased when PD-L1 was downregulated (opposite effects for PD-L1 upregulation). In mouse models, radiotherapy, CDK4/6-inhibitors, and RB deletion induced PD-L1-upregulation, causing PC-immune-evasion. Epigenetic drugs may reduce PD-L1 expression. In some PC experimental models, blocking only the PD-1/PD-L1 pathway had limited efficacy in reducing the tumor growth. Anti-tumor effects could be increased by combining the PD-1/PD-L1 blockade with other approaches (inhibitors of tyrosine kinase, PI3K/mTOR or JAK/STAT3 pathways, p300/CBP; anti-RANKL and/or anti-CTLA-4 antibodies; cytokines; nitroxoline; DNA/cell vaccines; radiotherapy/Radium-223).
- Subjects
LABORATORY mice; PROGRAMMED death-ligand 1; INVESTIGATIONAL therapies; CELL lines; CELL migration; PROTEIN-tyrosine kinases
- Publication
International Journal of Molecular Sciences, 2021, Vol 22, Issue 22, p12297
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms222212297