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)

Andrea Palicelli, Stefania Croci, Alessandra Bisagni, Eleonora Zanetti, Dario De Biase, Beatrice Melli, Francesca Sanguedolce, Moira Ragazzi, Magda Zanelli, Alcides Chaux, Sofia Cañete-Portillo, Maria Paola Bonasoni, Alessandra Soriano, Stefano Ascani, Maurizio Zizzo, Carolina Castro Ruiz, Antonio De Leo, Guido Giordano, Matteo Landriscina, Giuseppe CarrieriLuigi Cormio, Daniel M. Berney, Jatin Gandhi, Giacomo Santandrea, Martina Bonacini

Research output: Contribution to journalReview articlepeer-review

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).

Original languageEnglish
Article number12297
JournalInternational Journal of Molecular Sciences
Volume22
Issue number22
DOIs
Publication statusPublished - Nov 1 2021

Keywords

  • Cancer
  • Checkpoint inhibitors
  • Immunotherapy
  • Microenvironment
  • PD-L1
  • Prostate
  • Signaling pathways
  • Target-therapy

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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