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Synergistic immunochemotherapy exerts efficiently anti-hepatocellular carcinoma effect to induce SAMD4B-APOA2 axis for inhibition of tumor immune evasion [NM-seq]

ABSTRACT: RNA modifications are a type of post-transcriptional modification and involved in many biological processes of immune cells, thus regulating immune response and participating in immune related diseases. 2'-O-methylation is one of the most common modifications. However, whether 2’-O-methylation is involved in immune evasion via regulating programmed death ligand 1 (PD-L1) is unclear. Here, we were the first to propose a new treatment strategy for patients with advanced hepatocellular carcinoma (HCC), provided evidence that synergistic immunochemotherapy had a better prognosis, and revealing the mechanism of immune regulation through 2'-O-methylation modification mediated by SAMD4B, as a tumor suppressor gene.

ORGANISM(S): Homo sapiens

PROVIDER: GSE223622 | GEO | 2024/01/21

REPOSITORIES: GEO

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Project description:BackgroundCombination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy.MethodsIn the present study, we examined the expression of TIGIT using a preclinical mouse model treated with MWA. Moreover, we evaluated the antitumor functions of MWA alone or in combination with TIGIT blockade by monitoring tumor growth and survival of the mice. Besides, we also detected the numbers of tumor-infiltrating lymphocytes (TILs), and effector molecules of CD8+ T cells using flow cytometry. Finally, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups.ResultsThe expression of TIGIT in various immune cells was up-regulated after MWA, and the addition of TIGIT blockade to MWA prolonged survival and delayed tumor growth in the MC38 tumor model. Taken together, our findings showed that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME) using flow cytometry and scRNA-seq analysis.ConclusionsTIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.

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Synergistic immunochemotherapy exerts efficiently anti-hepatocellular carcinoma effect to induce SAMD4B-APOA2 axis for inhibition of tumor immune evasion [NM-seq]

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