A scoping review on the potentiality of PD-L1-inhibiting microRNAs in treating colorectal cancer: Toward single-cell sequencing-guided biocompatible-based delivery

• Published in: Biomedicine & pharmacotherapy Vol. 143; p. 112213
• Main Authors: Shadbad, Mahdi Abdoli, Asadzadeh, Zahra, Derakhshani, Afshin, Hosseinkhani, Negar, Mokhtarzadeh, Ahad, Baghbanzadeh, Amir, Hajiasgharzadeh, Khalil, Brunetti, Oronzo, Argentiero, Antonella, Racanelli, Vito, Silvestris, Nicola, Baradaran, Behzad
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01-11-2021; Elsevier
• Subjects: Animals; B7-H1 Antigen - antagonists & inhibitors; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biocompatible carriers; Biocompatible Materials - administration & dosage; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Gene Transfer Techniques; Genetic Therapy; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; MicroRNAs; MicroRNAs - administration & dosage; MicroRNAs - genetics; MicroRNAs - metabolism; Nanomedicine; Nanoparticles; PD-L1; Personalized medicine; Signal Transduction; Single-cell sequencing; PD-L1; Single-cell sequencing; Personalized medicine; MicroRNAs; Biocompatible carriers; Colorectal cancer
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2021.112213

Tumoral programmed cell death ligand 1 (PD-L1) has been implicated in the immune evasion and development of colorectal cancer. Although monoclonal immune checkpoint inhibitors can exclusively improve the prognosis of patients with microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) colorectal cancer, specific tumor-suppressive microRNAs (miRs) can regulate multiple oncogenic pathways and inhibit the de novo expression of oncoproteins, like PD-L1, both in microsatellite stable (MSS) and MSI-H colorectal cancer cells. This scoping review aimed to discuss the currently available evidence regarding the therapeutic potentiality of PD-L1-inhibiting miRs for colorectal cancer. For this purpose, the Web of Science, Scopus, and PubMed databases were systematically searched to obtain peer-reviewed studies published before 17 March 2021. We have found that miR-191–5p, miR-382–3p, miR-148a-3p, miR‐93–5p, miR-200a-3p, miR-200c-3p, miR-138–5p, miR-140–3p, and miR-15b-5p can inhibit tumoral PD-L1 in colorectal cancer cells. Besides inhibiting PD-L1, miR-140–3p, miR-382–3p, miR-148a-3p, miR‐93–5p, miR-200a-3p, miR-200c-3p, miR-138–5p, and miR-15b-5p can substantially reduce tumor migration, inhibit tumor development, stimulate anti-tumoral immune responses, decrease tumor viability, and enhance the chemosensitivity of colorectal cancer cells regardless of the microsatellite state. Concerning the specific, effective, and safe delivery of these miRs, the single-cell sequencing-guided biocompatible-based delivery of these miRs can increase the specificity of miR delivery, decrease the toxicity of traditional nanoparticles, transform the immunosuppressive tumor microenvironment into the proinflammatory one, suppress tumor development, decrease tumor migration, and enhance the chemosensitivity of tumoral cells regardless of the microsatellite state.
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•Besides being an immune checkpoint, tumoral PD-L1 stimulates oncogenic pathways.•Immune checkpoint inhibitors do not substantially regulate oncogenic pathways.•Besides inhibiting PD-L1, PD-L1-inhibiting miRs can regulate tumoral pathways.•Biocompatible nanoparticles are safe and non-toxic carriers for miR delivery.•Single-cell sequencing data can facilitate personalized and specific miR delivery.