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).

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) / Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Santandrea, G.; Bonacini, M.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:22(2021), pp. 12297-12328. [10.3390/ijms222212297]

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)

Melli B.;Ragazzi M.;Zanelli M.;Zizzo M.;De Leo A.;Giordano G.;Landriscina M.;Santandrea G.;
2021

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 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).
2021
22
22
12297
12328
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) / Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Santandrea, G.; Bonacini, M.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:22(2021), pp. 12297-12328. [10.3390/ijms222212297]
Palicelli, A.; Croci, S.; Bisagni, A.; Zanetti, E.; De Biase, D.; Melli, B.; Sanguedolce, F.; Ragazzi, M.; Zanelli, M.; Chaux, A.; Canete-Portillo, S.; Bonasoni, M. P.; Soriano, A.; Ascani, S.; Zizzo, M.; Ruiz, C. C.; De Leo, A.; Giordano, G.; Landriscina, M.; Carrieri, G.; Cormio, L.; Berney, D. M.; Gandhi, J.; Santandrea, G.; Bonacini, M.
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