Evidence map›Paper›PMID 36223955›Full record

ArticleJournal for immunotherapy of cancer2022

Tripartite antigen-agnostic combination immunotherapy cures established poorly immunogenic tumors.

Sven Borchmann, Carolin Selenz, Mia Lohmann, Hanna Ludwig, Asmae Gassa, Johannes Brägelmann, Philipp Lohneis, Lydia Meder, Julia Mattlener, Sara Breid and 12 more

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

Article in Journal for immunotherapy of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.5field-weighted citation impact, top 33% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. γδ T cells and cancer.The Journal of clinical investigation · 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

22 authors at 4 institutions in 2 countries.

Sven BorchmannDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany sven.borchmann@uk-koeln.de roland.ullrich@uk-koeln.de.ORCID 0000-0001-6662-6864
Carolin SelenzDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Mia LohmannDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Hanna LudwigDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Asmae GassaDepartment of Cardiothoracic Surgery, University of Cologne, Cologne, Germany.
Johannes BrägelmannMildred Scheel School of Oncology, University Hospital Cologne, Medical Faculty, Cologne, Germany.
Philipp LohneisInstitute of Pathology, University of Cologne, Cologne, Germany.
Lydia MederDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Julia MattlenerDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Sara BreidDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Marieke NillDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Jana FassunkeInstitute of Pathology, University of Cologne, Cologne, Germany.
Amy J WisdomDepartment of Radiation Oncology and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Anik CompesDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Birgit GathofInstitute of Transfusion Medicine, University of Cologne, Cologne, Germany.
Hakan AlakusDepartment of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany.
David KirschDepartment of Radiation Oncology and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA.
Khosro HekmatDepartment of Cardiothoracic Surgery, University of Cologne, Cologne, Germany.
Reinhard BüttnerInstitute of Pathology, University of Cologne, Cologne, Germany.
H Christian ReinhardtDepartment of Hematology and Stem Cell Transplantation, University Hospital Essen,University Duisburg-Essen, German Cancer Consortium (DKTK partner site Essen), Essen, Germany.
Michael HallekDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany.
Roland T UllrichDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Cologne, Germany sven.borchmann@uk-koeln.de roland.ullrich@uk-koeln.de.
University of Cologne · DEDuke Medical Center · USEssen University Hospital · DEUniversity Hospital Cologne · DE

Funding

Dissecting the role of the immune system in the radiation response of Kras-mutant tumorsF30CA221268 · NCI · DUKE UNIVERSITY · PI WISDOM, AMY JORDAN · 2017 to 2020
$154k
NCI NIH HHS F30 CA221268
6 · The paper itself

Abstract

backgroundSingle-agent immunotherapy has shown remarkable efficacy in selected cancer entities and individual patients. However, most patients fail to respond. This is likely due to diverse immunosuppressive mechanisms acting in a concerted way to suppress the host anti-tumor immune response. Combination immunotherapy approaches that are effective in such poorly immunogenic tumors mostly rely on precise knowledge of antigenic determinants on tumor cells. Creating an antigen-agnostic combination immunotherapy that is effective in poorly immunogenic tumors for which an antigenic determinant is not known is a major challenge.

methodsWe use multiple cell line and poorly immunogenic syngeneic, autochthonous, and autologous mouse models to evaluate the efficacy of a novel combination immunotherapy named tripartite immunotherapy (TRI-IT). To elucidate TRI-ITs mechanism of action we use immune cell depletions and comprehensive tumor and immune infiltrate characterization by flow cytometry, RNA sequencing and diverse functional assays.

resultsWe show that combined adoptive cellular therapy (ACT) with lymphokine-activated killer cells, cytokine-induced killer cells, Vγ9Vδ2-T-cells (γδ-T-cells) and T-cells enriched for tumor recognition (CTLs) display synergistic antitumor effects, which are further enhanced by cotreatment with anti-PD1 antibodies. Most strikingly, the full TRI-IT protocol, a combination of this ACT with anti-PD1 antibodies, local immunotherapy of agonists against toll-like receptor 3, 7 and 9 and pre-ACT lymphodepletion, eradicates and induces durable anti-tumor immunity in a variety of poorly immunogenic syngeneic, autochthonous, as well as autologous humanized patient-derived models. Mechanistically, we show that TRI-IT coactivates adaptive cellular and humoral, as well as innate antitumor immune responses to mediate its antitumor effect without inducing off-target toxicity.

conclusionsOverall, TRI-IT is a novel, highly effective, antigen-agnostic, non-toxic combination immunotherapy. In this study, comprehensive insights into its preclinical efficacy, even in poorly immunogenic tumors, and mode of action are given, so that translation into clinical trials is the next step.

Indexed as

NeoplasmsToll-Like Receptor 3AnimalsCombined Modality TherapyEpitopesImmunotherapyMiceEpitopesToll-Like Receptor 3immunotherapylung neoplasmsmelanomasarcoma

Identifiers

PMID36223955
PMCPMC9562723
OpenAlexW4304695392

What OpenQuestion holds

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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.