Nature Biomedical Engineering, Published online: 06 October 2026; doi:10.1038/s41551-026-01786-5
A nanoscale metal–organic framework (MOF)-based cancer vaccine platform enables coordinated antigen presentation and innate immune activation, resulting in tumour regression, immune memory and protection against metastasis.
Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.
ABSTRACT
Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.
PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085
Cell Rep Med. 2026 Oct 2:103085. doi: 10.1016/j.xcrm.2026.103085. Online ahead of print.
ABSTRACT
Hepatocellular carcinoma (HCC) management is challenging due to its complex tumor microenvironment and poor treatment responses. Here, using tumor specimens from a prospective clinical trial of combined transarterial chemoembolization (TACE) with immune checkpoint blockade (ICB), we perform exhaustive multi-omics analysis including spatial proteomics and transcriptomics, single-cell RNA sequencing, and bulk transcriptomics. These analyses reveal that treatment response is associated with enrichment of anti-tumor T cell regions that are regulated by cGAS-STING activation within immune-suppressive epithelial cells. Conversely, fibrotic processes impede these pro-response processes. Based on these insights, we test triple combination therapy consisting of cGAS activation, immune checkpoint blockade, and anti-fibrosis strategies, which shows improved efficacy over dual therapy. To identify patients who would benefit, we construct a predictive model using a group sparse learning algorithm. Our findings provide a blueprint for crafting personalized HCC therapies using next-generation biomarkers.
PMID:42826719 | DOI:10.1016/j.xcrm.2026.103085
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