Evidence map›Paper›PMID 36551634›Full record

ArticleCancers2022

Anti-Programmed Cell Death-1 Antibody and Dasatinib Combination Therapy Exhibits Efficacy in Metastatic Colorectal Cancer Mouse Models.

Hiroki Kadota, Ryo Yuge, Daisuke Shimizu, Ryo Miyamoto, Rina Otani, Yuichi Hiyama, Hidehiko Takigawa, Ryohei Hayashi, Yuji Urabe, Yasuhiko Kitadai and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

16 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
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  11. Consideration on immunotherapy of liver metastases of malignant tumors.World journal of gastrointestinal surgery · 2024
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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

12 authors at 2 institutions in 1 country.

Hiroki KadotaDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.ORCID 0000-0002-5729-0825
Ryo YugeDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Daisuke ShimizuDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Ryo MiyamotoDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Rina OtaniDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Yuichi HiyamaClinical Research Center in Hiroshima, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Hidehiko TakigawaDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan.ORCID 0000-0001-6369-0641
Ryohei HayashiDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Yuji UrabeDepartment of Gastroenterointestinal Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Yasuhiko KitadaiDepartment of Health Sciences, Prefectural University of Hiroshima, Hiroshima 734-8558, Japan.
Shiro OkaDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Shinji TanakaDepartment of Endoscopy, Hiroshima University Hospital, Hiroshima 734-8551, Japan.
Hiroshima University Hospital · JPPrefectural University of Hiroshima · JP

Funding

Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KA-KENHI) grant JP21K158533
6 · The paper itself

Abstract

In this study, we investigated the in vivo metastasis suppression effects of the platelet-derived growth factor receptor inhibitor dasatinib, which targets cancer-associated fibroblasts (CAFs), in combination with an anti-programmed cell death-1 (PD-1) antibody. We classified clinical CRC cases as inflamed, excluded, or desert using immunohistochemical analysis and evaluated the tumor stroma. The excluded type was the most common, and cases with high-volume stroma in the primary lesions also had a high stromal volume in the liver metastatic lesions. Liver-metastasis mouse models with different stromal volumes were established and treatment-induced changes in the tumor immune microenvironment were evaluated. The anti-PD-1 antibody alone exhibited a therapeutic effect for the liver metastases with low stromal volumes but not for the liver metastases with high stromal volumes. In contrast, antitumor effects were observed with anti-PD-1 antibody/dasatinib combination therapy even in the liver metastases with high stromal volumes. Combination therapy reduced the stromal volume, promoted immune cell infiltration, induced antitumor cytotoxic T-cell responses, activated antitumor immunity, and promoted tumor regression. These results suggest that CAFs play an important role in the immune evasion of CRC and that anti-PD-1 antibody/dasatinib combination therapy has potential as a treatment option for patients with metastatic CRC for whom immunotherapy alone is ineffective.

Indexed as

cancer-associated fibroblastsdasatinibmetastatic colorectal cancerplatelet-derived growth factor receptorprogrammed cell death-1 antibody

Identifiers

PMID36551634
PMCPMC9776338
OpenAlexW4311366706

What OpenQuestion holds

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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.