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Role of regorafenib in antitumor immunity in hepatocellular carcinoma

ABSTRACT: Role of regorafenib in antitumor immunity in hepatocellular carcinoma

PROVIDER: PRJNA626615 | ENA |

REPOSITORIES: ENA

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Role of regorafenib in antitumor immunity in hepatocellular carcinoma

Project description:Low-dose regorafenib (5 mg/kg/day, corresponding to about half of human clinical dosage) inhibited tumor growth and angiogenesis in vivo similarly to DC-101 (anti-VEGFR antibody) but produced higher T cell activation and M1 macrophage polarization, Regorafenib increased M1/M2 ratio of BMDMs polarization and proliferation/activation of co-cultured T cells in vitro, indicating angiogenesis-independent immunomodulatory effects. Suppression of p38 kinase phosphorylation and downstream CREB-KLF4 activity in BMDMs by regorafenib reversed M2 polarization. Regorafenib enhanced antitumor efficacy of adoptively transferred antigen-specific T cells, whereas macrophage deletion negated regorafenib’s antitumor effects. Synergistic antitumor efficacy between low-dose regorafenib and anti-PD1 was associated with multiple immune-related pathways in the tumor microenvironment.

2021-01-27 | GSE148947 | GEO

Role of regorafenib in macrophage and in antitumor immunity in hepatocellular carcinoma

Project description:Role of regorafenib in macrophage and in antitumor immunity in hepatocellular carcinoma

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Role of regorafenib in macrophage

Project description:Regorafenib increased M1/M2 ratio of BMDMs polarization and proliferation/activation of co-cultured T cells in vitro, indicating angiogenesis-independent immunomodulatory effects. Suppression of p38 kinase phosphorylation and downstream CREB-KLF4 activity in BMDMs by regorafenib reversed M2 polarization. Regorafenib enhanced antitumor efficacy of adoptively transferred antigen-specific T cells, whereas macrophage deletion negated regorafenib’s antitumor effects. Synergistic antitumor efficacy between low-dose regorafenib and anti-PD1 was associated with multiple immune-related pathways in the tumor microenvironment.

2021-01-27 | GSE148948 | GEO

Transcriptomic changes induced by regorafenib in sorafenib-resistant hepatocellular carcinoma cells: role of TGF-beta signaling and lncRNAs

Project description:We comprehensively analyzed the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) underlying the antitumor functions of regorafenib of sorafenib-resistant HCC cells using RNA sequencing (RNA-Seq). The treatment with regorafenib has demonstrated the ability to reverse the expression of genes and long non-coding RNAs (lncRNAs) that play crucial roles in signal pathways and epigenetic processes.

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Role and efficacy of the ironized anti-PD1 inhibitors in antitumor immunity in hepatocellular carcinoma

Project description:Role and efficacy of the ironized anti-PD1 inhibitors in antitumor immunity in hepatocellular carcinoma

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Role of regorafenib in macrophage and in antitumor immunity in hepatocellular carcinoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-27 | GSE148950 | GEO

A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma

Project description:A selective HDAC8 inhibitor potentiates antitumor immunity and efficacy of immune checkpoint blockade in hepatocellular carcinoma

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SETDB1-TRIM28 complex suppresses antitumor immunity

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Differential T-cell and monocyte responses in hepatocellular carcinoma treated with regorafenib plus nivolumab: an integrated clinical and biomarker analysis of the phase 2 RENOBATE trial

Project description:Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib-nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709 .

2023-12-31 | GSE243572 | GEO

Role of regorafenib in macrophage

Project description:Role of regorafenib in macrophage

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