The RNA-Binding Protein RBM3 Promotes Cell Proliferation in Hepatocellular Carcinoma by Regulating Circular RNA SCD-circRNA 2 Production

2019 ◽  
Author(s):  
Wei Dong ◽  
Zhi-hui Dai ◽  
Fu-chen Liu ◽  
Xing-gang Guo ◽  
Chun-mei Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Circular Rna

scholarly journals The RNA-binding protein RBM3 promotes cell proliferation in hepatocellular carcinoma by regulating circular RNA SCD-circRNA 2 production

EBioMedicine ◽  
2019 ◽  
Vol 45 ◽  
pp. 155-167 ◽  
Author(s):  
Wei Dong ◽  
Zhi-hui Dai ◽  
Fu-chen Liu ◽  
Xing-gang Guo ◽  
Chun-mei Ge ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Circular Rna

scholarly journals Cold-Inducible RNA Binding Protein as a Vaccination Platform to Enhance Immunotherapeutic Responses against Hepatocellular Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3397
Author(s):  
Leyre Silva ◽  
Josune Egea ◽  
Lorea Villanueva ◽  
Marta Ruiz ◽  
Diana Llopiz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cell ◽  
Rna Binding ◽  
Checkpoint Inhibitors ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
T Cell Responses ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Responses ◽  
Tlr4 Ligand

Therapies based on immune checkpoint inhibitors (ICPI) have yielded promising albeit limited results in patients with hepatocellular carcinoma (HCC). Vaccines have been proposed as combination partners to enhance response rates to ICPI. Thus, we analyzed the combined effect of a vaccine based on the TLR4 ligand cold-inducible RNA binding protein (CIRP) plus ICPI. Mice were immunized with vaccines containing ovalbumin linked to CIRP (OVA-CIRP), with or without ICPI, and antigen-specific responses and therapeutic efficacy were tested in subcutaneous and orthotopic mouse models of liver cancer. OVA-CIRP elicited polyepitopic T-cell responses, which were further enhanced when combined with ICPI (anti-PD-1 and anti-CTLA-4). Combination of OVA-CIRP with ICPI enhanced ICPI-induced therapeutic responses when tested in subcutaneous and intrahepatic B16-OVA tumors, as well as in the orthotopic PM299L HCC model. This effect was associated with higher OVA-specific T-cell responses in the periphery, although many tumor-infiltrating lymphocytes still displayed an exhausted phenotype. Finally, a new vaccine containing human glypican-3 linked to CIRP (GPC3-CIRP) induced clear responses in humanized HLA-A2.01 transgenic mice, which increased upon combination with ICPI. Therefore, CIRP-based vaccines may generate anti-tumor immunity to enhance ICPI efficacy in HCC, although blockade of additional checkpoint molecules and immunosuppressive targets should be also considered.

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