Evidence map›Paper›PMID 36990268›Full record

ArticleCancer letters2023

scRNA-Seq and imaging mass cytometry analyses unveil iNKT cells-mediated anti-tumor immunity in pancreatic cancer liver metastasis.

Qijun Yi, Jie Wang, Tingting Liu, Yi Yao, Ian Loveless, Kalpana Subedi, Jugmohit Toor, Indra Adrianto, Hua Xiao, Bin Chen and 4 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Cancer letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.3field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 20 citations in OpenAlex.

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  11. Single-cell multi-omics in the study of digestive system cancers.Computational and structural biotechnology journal · 2024
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Qijun YiCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Jie WangCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Tingting LiuCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Yi YaoCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Ian LovelessCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, MI, 48202, USA.
Kalpana SubediCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Jugmohit ToorCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA.
Indra AdriantoCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, MI, 48202, USA; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, 48824, USA.
Hua XiaoDepartment of Physiology, College of Natural Science, Michigan State University, East Lansing, MI, 48824, USA.
Bin ChenDepartment of Pediatrics and Human Development, Michigan State University, Grand Rapids, MI, USA.
Howard C CrawfordHenry Ford Pancreatic Cancer Center, Department of Surgery, Henry Ford Health, Detroit, MI, 48202, USA.
Deyu FangDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Li ZhouCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, MI, 48202, USA; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, 48824, USA; Department of Internal Medicine, Henry Ford Health, Detroit, MI, 48202, USA. Electronic address: lzhou1@hfhs.org.
Qing-Sheng MiCenter for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI, 48202, USA; Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI, 48202, USA; Center for Bioinformatics, Department of Public Health Sciences, Henry Ford Health, Detroit, MI, 48202, USA; Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI, 48824, USA; Department of Internal Medicine, Henry Ford Health, Detroit, MI, 48202, USA. Electronic address: QMI1@hfhs.org.
Henry Ford Health System · USMichigan State University · USNorthwestern University · US

Funding

A deubiquitination module controls Treg adaptation to tumor microenvironmentR01CA257520 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI FANG, DEYU, ZHANG, BIN · 2021 to 2025
$2.8M
microRNAs and NKT cell development and functionR01AI119041 · NIAID · HENRY FORD HEALTH SYSTEM · PI MI, QING-SHENG · 2016 to 2020
$1.8M
Targeting a Treg deubiquitinase in antitumor immune therapyR01CA232347 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI FANG, DEYU · 2018 to 2022
$1.7M
MicroRNAs regulate skin Langerhans cellsR01AR072046 · NIAMS · HENRY FORD HEALTH SYSTEM · PI ZHOU, LI · 2018 to 2022
$1.6M
Uncover the new subsets of epidermal Langerhans cellsR33AR076803 · NIAMS · HENRY FORD HEALTH SYSTEM · PI ADRIANTO, INDRA, MI, QING-SHENG · 2021 to 2021
$380k
NCI NIH HHS R01 CA232347NCI NIH HHS R01 CA257520NIAID NIH HHS R01 AI119041NIAMS NIH HHS R01 AR072046NIAMS NIH HHS R33 AR076803
6 · The paper itself

Abstract

Invariant natural killer T (iNKT) cells are innate-like T cells that are abundant in liver sinusoids and play a critical role in tumor immunity. However, the role of iNKT cells in pancreatic cancer liver metastasis (PCLM) has not been fully explored. In this study, we employed a hemi-spleen pancreatic tumor cell injection mouse model of PCLM, a model that closely mimics clinical conditions in humans, to explore the role of iNKT cells in PCLM. Activation of iNKT cells with α-galactosylceramide (αGC) markedly increased immune cell infiltration and suppressed PCLM progression. Via single cell RNA sequencing (scRNA-seq) we profiled over 30,000 immune cells from normal liver and PCLM with or without αGC treatment and were able to characterize the global changes of the immune cells in the tumor microenvironment upon αGC treatment, identifying a total of 12 subpopulations. Upon treatment with αGC, scRNA-Seq and flow cytometry analyses revealed increased cytotoxic activity of iNKT/NK cells and skewing CD4 T cells towards a cytotoxic Th1 profile and CD8 T cells towards a cytotoxic profile, characterized by higher proliferation and reduced exhaustion marker PD1 expression. Moreover, αGC treatment excluded tumor associated macrophages. Lastly, imaging mass cytometry analysis uncovered the reduced epithelial to mesenchymal transition related markers and increased active CD4 and CD8 T cells in PCLM with αGC treatment. Overall, our findings uncover the protective function of activated iNKT cells in pancreatic cancer liver metastasis through increased NK and T cell immunity and decreased tumor associated macrophages.

Indexed as

Liver NeoplasmsNatural Killer T-CellsPancreatic NeoplasmsAnimalsEpithelial-Mesenchymal TransitionHumansImage CytometryLymphocyte ActivationMiceSingle-Cell Gene Expression AnalysisTumor MicroenvironmentCD4 TCD8 T cellInvariant natural killer T(iNKT) cellsPancreatic cancer liver metastasisscRNA-seqTumor immunityα-galactosylceramide (αGC)

Identifiers

PMID36990268
PMCPMC11737350
OpenAlexW4360983076

What OpenQuestion holds

Textmetadata
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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.