Evidence map›Paper›PMID 37487666›Full record

ArticleJournal for immunotherapy of cancer2023

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

Michael Chiorazzi, Jan Martinek, Bradley Krasnick, Yunjiang Zheng, Keenan J Robbins, Rihao Qu, Gabriel Kaufmann, Zachary Skidmore, Melani Juric, Laura A Henze and 24 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
5.1field-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

34 citing papers in PubMed, 31 citations in OpenAlex.

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  10. Choosing the right animal model for sarcoma research.Cellular and molecular life sciences : CMLS · 2026
    Review
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  17. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.Proceedings of the National Academy of Sciences of the United States of America · 2025
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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

34 authors at 5 institutions in 1 country.

Michael ChiorazziDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0001-6289-3893
Jan MartinekJackson Laboratory - Farmington, Farmington, Connecticut, USA.
Bradley KrasnickAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Yunjiang ZhengDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Keenan J RobbinsAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Rihao QuDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Gabriel KaufmannDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Zachary SkidmoreAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Melani JuricDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Laura A HenzeDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Frederic BröseckeDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.ORCID 0000-0003-2468-0824
Adam AdonyiDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Jun ZhaoDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Liang ShanDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Esen SefikDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA.
Jacqueline MuddAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Ye BiAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
S Peter GoedegebuureAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Malachi GriffithAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Obi GriffithAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Abimbola OyedejiAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Sofia FertuzinhosBioinformatics Support Program, Cushing/Whitney Medical Library, Yale School of Medicine, New Haven, Connecticut, USA.
Rolando Garcia-MilianBioinformatics Support Program, Cushing/Whitney Medical Library, Yale School of Medicine, New Haven, Connecticut, USA.
Daniel BoffaDepartment of Surgery, Section of Thoracic Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Frank DetterbeckDepartment of Surgery, Section of Thoracic Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Andrew DhanasoponDepartment of Surgery, Section of Thoracic Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Justin BlasbergDepartment of Surgery, Section of Thoracic Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Benjamin JudsonDepartment of Surgery, Section of Otolaryngology, Yale School of Medicine, New Haven, Connecticut, USA.
Scott GettingerDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Katerina PolitiDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, Connecticut, USA.
Yuval KlugerDepartment of Pathology, Yale School of Medicine, New Haven, Connecticut, USA.
Karolina PaluckaJackson Laboratory - Farmington, Farmington, Connecticut, USA.
Ryan C FieldsAlvin J Siteman Cancer Center, St Louis, Missouri, USA.
Richard A FlavellDepartment of Immunobiology, Yale School of Medicine, New Haven, Connecticut, USA richard.flavell@yale.edu.ORCID 0000-0003-4461-0778
Yale University · USWashington University in St. Louis · USJackson Laboratory · USWhitney Museum of American Art · USHoward Hughes Medical Institute · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0M
Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung CancerP50CA196530 · NCI · YALE UNIVERSITY · PI Kurt A Schalper · 2015 to 2026
$31.1M
Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Nicholas O. Davidson · 2000 to 2026
$30.8M
Washington University PDX Development and Trial Center - Evaluation of Abemaciclib in Combination with Olaparib in Ovarian Cancer and Breast Cancer Patient-derived Xenograft ModelsU54CA224083 · NCI · WASHINGTON UNIVERSITY · PI Brian Andrew Van Tine · 2017 to 2026
$13.0M
SURGICAL ONCOLOGY TRAINING GRANTT32CA009621 · NCI · WASHINGTON UNIVERSITY · PI TIMOTHY J. EBERLEIN, William E. Gillanders · 1988 to 2026
$12.9M
Yale Head and Neck Cancer SPORE: Overcoming Treatment Resistance in Head and Neck CancerP50DE030707 · NIDCR · YALE UNIVERSITY · PI BURTNESS, BARBARA · 2020 to 2024
$11.8M
Washington University SPORE in Pancreatic CancerP50CA272213 · NCI · WASHINGTON UNIVERSITY · PI David G DeNardo, WILLIAM G HAWKINS · 2023 to 2026
$10.7M
IMMUNOHEMATOLOGY/TRANSFUSION MEDICINE RESEARCH TRAININGT32HL007974 · NHLBI · YALE UNIVERSITY · PI JEANNE E HENDRICKSON, Diane S Krause · 2001 to 2026
$8.1M
Advancing Precision Oncology in a Humanized, Fully Autologous Mouse ModelR01CA248277 · NCI · WASHINGTON UNIVERSITY · PI FIELDS, RYAN C, FLAVELL, RICHARD A · 2020 to 2024
$3.0M
NCATS NIH HHS UL1 TR001863NCI NIH HHS K08 CA245211NCI NIH HHS P30 CA016359NCI NIH HHS P30 CA034196NCI NIH HHS P30 CA091842NCI NIH HHS P50 CA196530NCI NIH HHS P50 CA272213NCI NIH HHS R01 CA204115NCI NIH HHS R01 CA248277NCI NIH HHS T32 CA009621NCI NIH HHS U54 CA224083NHLBI NIH HHS T32 HL007974NIDCR NIH HHS P50 DE030707NIDDK NIH HHS P30 DK052574
6 · The paper itself

Abstract

backgroundInteractions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

methodWith patient-derived bone marrow hematopoietic stem and progenitor cells (HSPCs), we engrafted a patient's hematopoietic system in MISTRG6 mice, followed by transfer of patient-derived xenograft (PDX) tissue, providing a fully genetically matched model to recapitulate the individual's TME. We used this system to prospectively study tumor-immune interactions in patients with solid tumor.

resultsAutologous PDX mice generated innate and adaptive immune populations; these cells populated the TME; and tumors from autologously engrafted mice grew larger than tumors from non-engrafted littermate controls. Single-cell transcriptomics revealed a prominent vascular endothelial growth factor A (VEGFA) signature in TME myeloid cells, and inhibition of human VEGF-A abrogated enhanced growth.

conclusionsHumanization of the interleukin 6 locus in MISTRG6 mice enhances HSPC engraftment, making it feasible to model tumor-immune interactions in an autologous manner from a bedside bone marrow aspirate. The TME from these autologous tumors display hallmarks of the human TME including innate and adaptive immune activation and provide a platform for preclinical drug testing.

Indexed as

NeoplasmsVascular Endothelial Growth Factor AAnimalsDisease Models, AnimalHumansMedical OncologyMiceTumor MicroenvironmentVascular Endothelial Growth Factor AImmunity, InnateImmunotherapyInflammationMacrophagesTumor Microenvironment

Identifiers

PMID37487666
PMCPMC10373695
OpenAlexW4385213217

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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.