TY - JOUR
T1 - 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)
AU - Palicelli, Andrea
AU - Croci, Stefania
AU - Bisagni, Alessandra
AU - Zanetti, Eleonora
AU - De Biase, Dario
AU - Melli, Beatrice
AU - Sanguedolce, Francesca
AU - Ragazzi, Moira
AU - Zanelli, Magda
AU - Chaux, Alcides
AU - Cañete-Portillo, Sofia
AU - Bonasoni, Maria Paola
AU - Soriano, Alessandra
AU - Ascani, Stefano
AU - Zizzo, Maurizio
AU - Ruiz, Carolina Castro
AU - De Leo, Antonio
AU - Giordano, Guido
AU - Landriscina, Matteo
AU - Carrieri, Giuseppe
AU - Cormio, Luigi
AU - Berney, Daniel M.
AU - Gandhi, Jatin
AU - Santandrea, Giacomo
AU - Bonacini, Martina
N1 - Funding Information:
Acknowledgments: Andrea Palicelli thanks his family for personal support. Daniel M. Berney is supported by Orchid and a PCUK grant.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11/14
Y1 - 2021/11/14
N2 - 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 immunotherapyresistance 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+ Tcells 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).
AB - 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 immunotherapyresistance 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+ Tcells 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).
KW - Cancer
KW - Checkpoint inhibitors
KW - Immunotherapy
KW - Microenvironment
KW - PD-L1
KW - Prostate
KW - Signaling pathways
KW - Target-therapy
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U2 - 10.3390/ijms222212297
DO - 10.3390/ijms222212297
M3 - Review article
AN - SCOPUS:85118948566
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 22
M1 - 12297
ER -