Evidence map›Paper›PMID 36278484›Full record

ArticleJCI insight2022

Intraperitoneal injection of class A TLR9 agonist enhances anti-PD-1 immunotherapy in colorectal peritoneal metastases.

Ting Jiang, Hongji Zhang, Yiming Li, Preethi Jayakumar, Hong Liao, Hai Huang, Timothy R Billiar, Meihong Deng

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

7 citing papers in PubMed, 6 citations in OpenAlex.

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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 at 3 institutions in 2 countries.

Ting JiangDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Hongji ZhangDepartment of Surgery, The Ohio State University, Columbus, Ohio, USA.
Yiming LiDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Preethi JayakumarDepartment of Surgery, The Ohio State University, Columbus, Ohio, USA.
Hong LiaoDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Hai HuangDepartment of Surgery, The Ohio State University, Columbus, Ohio, USA.
Timothy R BilliarDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Meihong DengDepartment of Surgery, The Ohio State University, Columbus, Ohio, USA.
University of Pittsburgh · USFeinstein Institute for Medical Research · USUniversity of Virginia · US

Funding

Mechanisms of Immune Dysfunction after Trauma and Surgical SepsisR35GM127027 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI TIMOTHY R BILLIAR · 2018 to 2026
$5.7M
Role of Toll-like Receptor 9 in Fibroblastic Reticular Cell-based Therapy for Intra-abdominal SepsisR01AI152044 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DENG, MEIHONG · 2020 to 2024
$2.1M
Preoperative exercise therapy triggers trained immunity in KCs via cholinergic anti-inflammatory pathwayR01GM137203 · NIGMS · OHIO STATE UNIVERSITY · PI HUANG, HAI · 2020 to 2025
$2.0M
NIAID NIH HHS R01 AI152044NIGMS NIH HHS R01 GM137203NIGMS NIH HHS R35 GM127027
6 · The paper itself

Abstract

Peritoneal metastases are associated with a low response rate to immune checkpoint blockade (ICB) therapy. The numbers of peritoneal resident macrophages (PRMs) are reversely correlated with the response rate to ICB therapy. We have previously shown that TLR9 in fibroblastic reticular cells (FRCs) plays a critical role in regulating peritoneal immune cell recruitment. However, the role of TLR9 in FRCs in regulating PRMs is unclear. Here, we demonstrated that the class A TLR9 agonist, ODN1585, markedly enhanced the efficacy of anti-PD-1 therapy in mouse models of colorectal peritoneal metastases. ODN1585 injected i.p. reduced the numbers of Tim4+ PRMs and enhanced CD8+ T cell antitumor immunity. Mechanistically, treatment of ODN1585 suppressed the expression of genes required for retinoid metabolism in FRCs, and this was associated with reduced expression of the PRM lineage-defining transcription factor GATA6. Selective deletion of TLR9 in FRCs diminished the benefit of ODN1585 in anti-PD-1 therapy in reducing peritoneal metastases. The crosstalk between PRMs and FRCs may be utilized to develop new strategies to improve the efficacy of ICB therapy for peritoneal metastases.

Indexed as

Colorectal NeoplasmsPeritoneal NeoplasmsAdjuvants, ImmunologicAnimalsGATA6 Transcription FactorImmune Checkpoint InhibitorsImmunotherapyInjections, IntraperitonealMiceRetinoidsToll-Like Receptor 9Adjuvants, ImmunologicGATA6 Transcription FactorImmune Checkpoint InhibitorsRetinoidsTlr9 protein, mouseToll-Like Receptor 9Cancer immunotherapyImmunologyMacrophagesOncology

Identifiers

PMID36278484
PMCPMC9714777
OpenAlexW4307106009

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.