Evidence map›Paper›PMID 29959458›Full record

ArticleCancer immunology, immunotherapy : CII2018

Indoleamine 2,3-dioxygenase provides adaptive resistance to immune checkpoint inhibitors in hepatocellular carcinoma.

Zachary J Brown, Su Jong Yu, Bernd Heinrich, Chi Ma, Qiong Fu, Milan Sandhu, David Agdashian, Qianfei Zhang, Firouzeh Korangy, Tim F Greten

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

Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

72 citing papers in PubMed, 110 citations in OpenAlex.

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12 more citing papers are in PubMed but not listed here.

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

10 authors at 2 institutions in 2 countries.

Zachary J BrownThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Su Jong YuThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Bernd HeinrichThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Chi MaThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Qiong FuThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Milan SandhuThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
David AgdashianThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Qianfei ZhangThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Firouzeh KorangyThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA.
Tim F GretenThoracic and GI Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Building 10, Room 3B43, Bethesda, MD, 20892, USA. tim.greten@nih.gov.ORCID http://orcid.org/0000-0002-0806-2535
National Institutes of Health · USNational Cancer Institute · US

Funding

Analysis of myeloid derived suppressor cells in miceZIABC011345 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GRETEN, TIM · 2010 to 2025
$19.5M
Clinical protocols for the treatment of GI cancerZIABC011343 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI GRETEN, TIM · 2010 to 2025
$4.8M
Intramural NIH HHS Z99 CA999999NCI NIH HHS ZIA BC 01134
6 · The paper itself

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. Immune checkpoint blockade with anti-CTLA-4 and anti-PD-1 antibodies has shown promising results in the treatment of patients with advanced HCC. The anti-PD-1 antibody, nivolumab, is now approved for patients who have had progressive disease on the current standard of care. However, a subset of patients with advanced HCC treated with immune checkpoint inhibitors failed to respond to therapy. Here, we provide evidence of adaptive resistance to immune checkpoint inhibitors through upregulation of indoleamine 2,3-dioxygenase (IDO) in HCC. Anti-CTLA-4 treatment promoted an induction of IDO1 in resistant HCC tumors but not in tumors sensitive to immune checkpoint blockade. Using both subcutaneous and hepatic orthotopic models, we found that the addition of an IDO inhibitor increases the efficacy of treatment in HCC resistant tumors with high IDO induction. Furthermore, in vivo neutralizing studies demonstrated that the IDO induction by immune checkpoint blockade was dependent on IFN-γ. Similar findings were observed with anti-PD-1 therapy. These results provide evidence that IDO may play a role in adaptive resistance to immune checkpoint inhibitors in patients with HCC. Therefore, inhibiting IDO in combination with immune checkpoint inhibitors may add therapeutic benefit in tumors which overexpress IDO and should be considered for clinical evaluation in HCC.

Indexed as

AnimalsAntibodies, MonoclonalCarcinoma, HepatocellularCell Line, TumorCTLA-4 AntigenHep G2 CellsHumansIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaLiver NeoplasmsMiceNivolumabProgrammed Cell Death 1 ReceptorAntibodies, MonoclonalCTLA-4 AntigenIndoleamine-Pyrrole 2,3,-DioxygenaseInterferon-gammaNivolumabProgrammed Cell Death 1 ReceptorAdaptive resistanceCTLA-4Hepatocellular carcinomaIDOPD-1

Identifiers

PMID29959458
PMCPMC6085109
OpenAlexW2809833956

What OpenQuestion holds

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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.