Evidence map›Paper›PMID 40234092›Full record

ArticleJournal for immunotherapy of cancer2025

CD155 blockade enhances allogeneic natural killer cell-mediated antitumor response against osteosarcoma.

Monica M Cho, Longzhen Song, Aicha E Quamine, Fernanda Szewc, Lei Shi, Johnathan D Ebben, David P Turicek, Jillian M Kline, Devin M Burpee, Emily O Lafeber and 7 more

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
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

10 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Monica M ChoDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.ORCID http://orcid.org/0000-0002-6708-9578
Longzhen SongDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Aicha E QuamineDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.ORCID http://orcid.org/0000-0002-9049-7078
Fernanda SzewcDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Lei ShiDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Johnathan D EbbenDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
David P TuricekDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Jillian M KlineDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Devin M BurpeeDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Emily O LafeberDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Madison F PhillipsDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Amanda S CeasDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Paul D BatesDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Matthew H ForsbergDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
John A KinkDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Amy K ErbeCarbone Cancer Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.ORCID http://orcid.org/0000-0003-1175-4062
Christian M CapitiniDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA ccapitini@pediatrics.wisc.edu.ORCID http://orcid.org/0000-0002-2276-6731

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
University of Wisconsin Institute for Clinical and Translational ResearchUL1TR002373 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI ELIZABETH S BURNSIDE, Allan R. Brasier · 2017 to 2026
$75.9M
Training in Cancer Biology Training GrantT32CA009135 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI SUGDEN, WILLIAM M. · 1985 to 2024
$10.4M
INTEGRATED TRAINING FOR PHYSICIAN-SCIENTISTST32GM008692 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BURKARD, MARK E · 1998 to 2020
$10.3M
NRSA Training CoreTL1TR002375 · NCATS · UNIVERSITY OF WISCONSIN-MADISON · PI Vivek Prabhakaran · 2017 to 2026
$8.4M
Combining hu14.18-IL2 and NK cell infusions to treat neuroblastomaR01CA215461 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CAPITINI, CHRISTIAN · 2018 to 2022
$1.7M
NCATS NIH HHS TL1 TR002375NCATS NIH HHS UL1 TR002373NCI NIH HHS P30 CA014520NCI NIH HHS R01 CA215461NCI NIH HHS T32 CA009135NIGMS NIH HHS T32 GM008692
6 · The paper itself

Abstract

backgroundAllogeneic bone marrow transplant (alloBMT) is curative for hematologic malignancies through the graft-versus-tumor (GVT) effect but has been ineffective for solid tumors like osteosarcoma (OS). OS expresses CD155 which interacts strongly with inhibitory receptors TIGIT and CD96 but also binds to activating receptor DNAM-1 on natural killer (NK) cells. CD155 has never been targeted after alloBMT. Combining adoptively transferred allogeneic NK (alloNK) cells with CD155 blockade after alloBMT may enhance a GVT effect against OS.

methodsMurine NK cells were activated and expanded ex vivo with superagonist interleukin (IL)-15/IL-15Rα. AlloNK and syngeneic NK (synNK) cell phenotype, cytotoxicity, cytokine production, and degranulation against CD155-expressing murine OS cell line K7M2 were assessed in vitro. Mice bearing pulmonary OS metastases underwent alloBMT and alloNK cell infusion with anti-CD155 either before or after tumor induction, with select groups receiving anti-DNAM-1 pretreated alloNK cells. Tumor growth, graft-versus-host disease and survival were monitored, and differential gene expression of lung tissue was assessed by RNA microarray.

resultsAlloNK cells exhibited superior cytotoxicity against CD155-expressing OS compared with synNK cells, and this activity was enhanced by CD155 blockade. CD155 blockade increased alloNK cell degranulation and interferon gamma production through DNAM-1. In vivo, CD155 blockade with alloNK infusion increased survival when treating OS that relapsed after alloBMT. No benefit was seen for treating established OS before alloBMT. Combining CD155 and anti-DNAM-1 pretreated alloNK did not affect survival and tumor control benefits seen with CD155 blockade alone. RNA microarray showed mice treated with alloNK and CD155 blockade had increased expression of cytotoxicity genes and the NKG2D ligand H60a, whereas mice treated with anti-DNAM-1 pretreated alloNK cells resulted in upregulation of NK cell inhibitory receptor genes. Whereas blocking DNAM-1 on alloNK abrogated cytotoxicity, blocking NKG2D had no effect, implying DNAM-1:CD155 engagement drives alloNK activation against OS.

conclusionsThese results demonstrate the safety and efficacy of infusing alloNK cells with CD155 blockade to mount a GVT effect against OS and show benefits are in part through DNAM-1. Defining the hierarchy of receptors that govern alloNK responses is critical to translating alloNK cell infusions and immune checkpoint inhibition for solid tumors treated with alloBMT.

Indexed as

Bone NeoplasmsKiller Cells, NaturalOsteosarcomaReceptors, VirusAnimalsCell Line, TumorFemaleGraft vs Tumor EffectHumansMiceT Lineage-Specific Activation Antigen 1poliovirus receptorReceptors, VirusT Lineage-Specific Activation Antigen 1Bone CancerNatural killer - NK

Identifiers

PMID40234092
PMCPMC12001373

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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.