Evidence map›Paper›PMID 41088223›Full record

ArticleMolecular cancer2025

Reversal of tumour immune evasion via enhanced MHC-Class-I antigen presentation by a dual-functional RNA regulated system.

Chaoyang Meng, Huipeng Zhang, Xuewen Yi, Gangcheng Kong, Xiaoge Zhang, Bei Wang, Yan Xu, Haoxiang Qi, Qing Wu, Ke Zhang and 8 more

Abstract read
In one paragraph

Article in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Defect-Engineered BiOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Chaoyang Meng *Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Huipeng Zhang *State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Xuewen Yi *Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Gangcheng Kong *Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Xiaoge ZhangState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Bei WangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Yan XuState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Haoxiang QiSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, China.
Qing WuState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Ke ZhangDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Jiaying CaoDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Xiaohan LinDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Huiheng FengState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Jianxiang ChenSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal, University Hangzhou Normal University, Hangzhou, 311121, China.
Shusen ZhengDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
Zhen GuState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
Hongjun LiState Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China. hongjun@zju.edu.cn.
Qi LingDepartment of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. lingqi@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMotivating the immune system to target tumour cells plays an increasingly prominent role in the treatment of hepatocellular carcinoma (HCC), but challenges such as low overall response rates persist in current clinical practice. Tumour cell MHC-Class-I (MHC-I) downregulation and antigen loss are typical mechanisms of immune evasion. To this end, a dual-functional RNA-based strategy was conceived for HCC immunotherapy.

methodsMHC-I expression on HCC and paratumour tissues from patients was assessed, and the correlations between MHC-I regulators and HCC prognosis were analyzed. Small interfering RNA (siRNA) targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) and mRNA encoding tumour antigens were encapsulated in a fluorinated lipid nanoparticle (LNP), which direct nucleic acids primarily to the liver, making it ideal for HCC treatment. Anti-tumour efficacy was investigated in an orthotopic HCC model, with single-cell RNA sequencing used for in-depth analysis of the tumour microenvironment (TME).

resultsA marked downregulation of MHC-I expression was observed in HCC tumour cells from a cohort of patients, with this MHC-I suppression correlating with poor prognosis and diminished responsiveness to immunotherapy. Among the various MHC-I regulators, PCSK9 is the only one that shows a significant correlation with the prognosis of HCC patients. Knockdown of PCSK9 inhibited MHC-I degradation and thus increased the efficiency of antigen presentation by up to sixfold compared to untreated tumour cells. The hybrid RNA LNPs (h-LNP) enhanced Th1-mediated immune responses, reinvigorating and expanding anti-tumour immunity within the TME. Following treatment with h-LNPs, the TME showed a pronounced infiltration of CD8

conclusionsThe present study successfully engineered a dual-functional RNA-regulated system that augments tumour cell antigen presentation and reconfigures the immune landscape within the TME, thereby potentiating the anti-tumour efficacy of the mRNA vaccine.

Indexed as

Antigen PresentationCarcinoma, HepatocellularHistocompatibility Antigens Class ILiver NeoplasmsTumor EscapeAnimalsAntigens, NeoplasmCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyMiceNanoparticlesPrognosisProprotein Convertase 9Antigens, NeoplasmHistocompatibility Antigens Class IProprotein Convertase 9RNA, Small InterferingDrug deliveryHepatocellular carcinomaRNA vaccineTumour immunotherapy

Identifiers

PMID41088223
PMCPMC12522306

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.