Evidence map›Paper›PMID 37880538›Full record

ArticleCommunications medicine2023

Lenvatinib activates anti-tumor immunity by suppressing immunoinhibitory infiltrates in the tumor microenvironment of advanced hepatocellular carcinoma.

Masami Yamauchi, Atsushi Ono, Kei Amioka, Yasutoshi Fujii, Hikaru Nakahara, Yuji Teraoka, Shinsuke Uchikawa, Hatsue Fujino, Takashi Nakahara, Eisuke Murakami and 14 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 3 pooled it
7.8field-weighted citation impact, top 2% of its field
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

31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 34 citations in OpenAlex.

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  7. Targeting Tumor-Associated Macrophages and Cancer-Associated Fibroblasts to Overcome Therapeutic Resistance in Hepatocellular Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 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

24 authors at 5 institutions in 1 country.

Masami YamauchiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. myamauchi@hiroshima-u.ac.jp.ORCID http://orcid.org/0000-0003-3573-5720
Atsushi OnoDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID http://orcid.org/0000-0002-2482-945X
Kei AmiokaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yasutoshi FujiiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hikaru NakaharaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Yuji TeraokaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Shinsuke UchikawaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hatsue FujinoDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.ORCID http://orcid.org/0000-0002-9691-4960
Takashi NakaharaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Eisuke MurakamiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Wataru OkamotoDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Daiki MikiDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Tomokazu KawaokaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masataka TsugeDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Michio ImamuraDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
C Nelson HayesDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Waka OhishiDepartment of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
Takeshi KishiDepartment of Clinical Studies, Radiation Effects Research Foundation, Hiroshima, Japan.
Mizuki KimuraOncology Department, HQs, Eisai Co., Ltd, Tokyo, Japan.
Natsumi SuzukiOncology Department, HQs, Eisai Co., Ltd, Tokyo, Japan.
Koji ArihiroDepartment of Anatomical Pathology, Hiroshima University Hospital, Hiroshima, Japan.
Hiroshi AikataDepartment of Gastroenterology, Hiroshima Prefectural Hospital, Hiroshima, Japan.
Kazuaki ChayamaCollaborative Research Laboratory of Medical Innovation, Hiroshima University, Hiroshima, Japan. chayama@mba.ocn.ne.jp.ORCID http://orcid.org/0000-0002-5530-5341
Shiro OkaDepartment of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. oka4683@hiroshima-u.ac.jp.ORCID http://orcid.org/0000-0002-1652-0743
Hiroshima University · JPEisai (Japan) · JPRadiation Effects Research Foundation · JPHiroshima Prefectural Hospital · JPHiroshima University Hospital · JP

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 20K16332MEXT | Japan Society for the Promotion of Science (JSPS) 22K15582
6 · The paper itself

Abstract

backgroundLenvatinib, a multiple receptor tyrosine kinase inhibitor, might exert antitumor effects via tumor immune modulation. However, changes in the tumor immune microenvironment induced by lenvatinib are poorly understood. We investigated the effect of lenvatinib on immune features in clinical samples from patients with hepatocellular carcinoma.

methodsFifty-one patients with advanced hepatocellular carcinoma who received lenvatinib monotherapy as first-line treatment were enrolled. We collected blood sample (n = 51) and tumor tissue (n, baseline/four weeks after treatment initiation/post-progression = 50/8/12). DNA, RNA, and proteins extracted from the tissues were subjected to multi-omics analysis, and patients were classified into two groups according to baseline immune status. Each group was investigated in terms of the dynamics of tumor signaling. We also longitudinally analyzed circulating immune proteins and chemokines in peripheral blood.

resultsHere we show that lenvatinib has similar anti-tumor efficacy with objective response rate and progression-free survival in both Immune-Hot and Immune-Cold subtypes. Immune signatures associated with T-cell functions and interferon responses are enriched in the early phase of treatment, while signatures associated with immunoinhibitory cells are downregulated along with efficient vascular endothelial growth factor receptor and fibroblast growth factor receptor blockades. These findings are supported by imaging mass cytometry, T-cell receptor repertoire analysis and kinetics of circulating proteins. We also identify interleukin-8 and angiopoietin-2 as possible targets of intervention to overcome resistance to existing immunotherapies.

conclusionsOur findings show the ability of lenvatinib to modulate tumor immunity in clinical samples of hepatocellular carcinoma.

Identifiers

PMID37880538
PMCPMC10600115
OpenAlexW4387938000

What OpenQuestion holds

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LicenceCC BY
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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.