Evidence map›Paper›PMID 39653551›Full record

ArticleJournal for immunotherapy of cancer2024

METTL3-VISTA axis-based combination immunotherapy for APC truncation colorectal cancer.

Ling Wu, Rui Bai, Yujie Zhang, Hao Chen, Jianghua Wu, Zetao Chen, Hui Wang, Liang Zhao

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
–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 synthesis or guideline pooled it.

  1. Pooled it
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  7. Review
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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

8 authors.

Ling Wu *Department of Pathology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China.
Rui Bai *Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Yujie Zhang *Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Hao ChenDepartment of Pathology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China.
Jianghua WuDepartment of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.
Zetao ChenDepartment of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Hui WangDepartment of Medical Oncology, Guangzhou Medical University Affiliated Cancer Hospital, Guangzhou, Guangdong, China.
Liang ZhaoDepartment of Pathology, Shunde Hospital of Southern Medical University, Foshan, Guangdong, China liangsmu@foxmail.com.ORCID 0000-0002-1429-0884

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveAlthough immune checkpoint blockade (ICB) therapy represents a bright spot in antitumor immunotherapy, its clinical benefits in colorectal cancer (CRC) are limited. Therefore, a new target for mediating CRC immunosuppression is urgently needed. Adenomatous polyposis coli (APC) mutations have been reported as early-stage characteristic events in CRC, but the role of truncated APC in the CRC immune microenvironment remains unclear and its clinical significance has yet to be explored.

designAdenocarcinoma formation in the colon of the APC

resultsWe showed that APC978∆, a truncated APC protein, mediated overexpression of METTL3, resulting in m6A methylation of HIF1α messenger RNA and high expression of HIF1α. Furthermore, HIF1α promotes the migration of myeloid-derived suppressor cells to the TME by binding to the promoters of MCP-1 and MIF. In addition, HIF1α enhances the expression of the immune checkpoint VISTA on CRC cells, weakening tumor immune monitoring.

conclusionsWe elucidate that an underappreciated function of truncated APC in CRC is its ability to drive an immunosuppressive program that boosts tumor progression. Our work could provide a new perspective for the clinical application of immunotherapy in patients with CRC resistant to ICB therapy.

Indexed as

Colorectal NeoplasmsImmunotherapyMethyltransferasesAdenomatous Polyposis Coli ProteinAnimalsDisease Models, AnimalHumansMiceTumor MicroenvironmentAdenomatous Polyposis Coli ProteinMethyltransferasesMETTL3 protein, humanColorectal CancerImmunotherapy

Identifiers

PMID39653551
PMCPMC11629097

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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.