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 and Croci S and Bisagni A and Zanetti E and De Biase D and Melli B and Sanguedolce F and Ragazzi M and Zanelli M and Chaux A and Cañete-Portillo S and Bonasoni MP and Soriano A and Ascani S and Zizzo M and Castro Ruiz C and De Leo A and Giordano G and Landriscina M and Carrieri G and Cormio L and Berney DM and Gandhi J and Santandrea G and Bonacini M

International journal of molecular sciences (2021) 22:

DOI: 10.3390/ijms222212297

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).

Citation

Palicelli A, Croci S, Bisagni A, Zanetti E, De Biase D, Melli B, Sanguedolce F, Ragazzi M, Zanelli M, Chaux A, Cañete-Portillo S, Bonasoni MP, Soriano A, Ascani S, Zizzo M, Castro Ruiz C, De Leo A, Giordano G, Landriscina M, … Bonacini M. (2021). 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). International Journal of Molecular Sciences, 22(22). https://doi.org/10.3390/ijms222212297 Animals, Male, Humans, Mice, Cell Line, Tumor, Immunotherapy/*methods, *Disease Models, Animal, Signal Transduction/genetics/*immunology, Prostatic Neoplasms, B7-H1 Antigen/genetics/*immunology/metabolism, Gene Expression Regulation, Neoplastic/immunology, Prostatic Neoplasms/genetics/immunology/*therapy

Keywords

• Animals
• Male
• Humans
• Mice
• Cell Line
• Tumor
• Immunotherapy/*methods
• *Disease Models
• Animal
• Signal Transduction/genetics/*immunology
• Prostatic Neoplasms
• B7-H1 Antigen/genetics/*immunology/metabolism
• Gene Expression Regulation
• Neoplastic/immunology
• Prostatic Neoplasms/genetics/immunology/*therapy