Evidence map›Paper›PMID 40928975›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025

Immunocompetent Murine Models Recapitulate the Heterogeneous Tumor-Immune Microenvironment of Human Liposarcoma.

Amanda M Shafer, Emma Kenna, Lexi-Ann F Golden, Ahmed M Elhossiny, Kyle D Perry, Jodi Wilkowski, Wei Yan, Brynn Kaczkofsky, Jake McGue, Scott C Bresler and 11 more

Abstract read
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors.

Amanda M Shafer *Department of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0008-6959-1968
Emma Kenna *Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-8171-3640
Lexi-Ann F Golden *Program in Cancer Biology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-7724-0932
Ahmed M ElhossinyDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-0884-8754
Kyle D PerryDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-6238-5768
Jodi WilkowskiDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-7382-8832
Wei YanDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0006-9548-6307
Brynn KaczkofskyDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0000-1399-6044
Jake McGueDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-6131-7798
Scott C BreslerDepartment of Pathology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-2504-466X
Adam H CourtneyRogel Cancer Center, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0003-2829-1236
Jessie M DalmanDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0003-9373-7035
Craig J GalbánDepartment of Radiology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-5596-7487
Wei JiangDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-2737-4913
Carlos E EspinozaDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0009-0000-0460-1514
Rashmi ChughDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-4633-6971
Matthew K IyerDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-0217-7390
Timothy L FrankelDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-5987-0404
Marina Pasca di MaglianoDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0001-9632-9035
Andrzej A DlugoszDepartment of Dermatology, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-9791-3257
Christina V AngelesDepartment of Surgery, University of Michigan, Ann Arbor, Michigan.ORCID 0000-0002-6500-9589

Funding

XenograftP30CA046592 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Veerabhadran Baladandayuthapani · 1988 to 2026
$178.2M
University of Michigan Skin Biology and Diseases Resource-based CenterP30AR075043 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Johann Eli Gudjonsson · 2019 to 2026
$6.6M
Cell fate decisions in Merkel cell carcinoma initiation and maintenanceR01CA241947 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DLUGOSZ, ANDRZEJ A., VERHAEGEN, MONIQUE ELISE · 2020 to 2024
$2.6M
Ultrasound-guided Ultra-steerable Histotripsy Array System for Non-invasive treatment of Soft Tissue SarcomaR01EB034399 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Zhen Xu · 2023 to 2026
$2.2M
Training Program in Translational ResearchT32GM141840 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANDREW P LIEBERMAN, Zaneta Nikolovska-Coleska · 2021 to 2026
$2.0M
Genetically engineered mouse models to investigate the liposarcoma microenvironmentR03CA280126 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ANGELES, CHRISTINA VADALA · 2024 to 2025
$156k
National Cancer Institute (NCI) P30CA046592National Cancer Institute (NCI) R03CA280126National Institute of Biomedical Imaging and Bioengineering (NIBIB) R01EB034399National Institute of General Medical Sciences (NIGMS) T32GM141840NCI NIH HHS P30 CA046592NCI NIH HHS R01 CA241947NCI NIH HHS R03 CA280126NIAMS NIH HHS P30 AR075043NIBIB NIH HHS R01 EB034399NIGMS NIH HHS T32 GM141840
6 · The paper itself

Abstract

purposeLiposarcoma is the most common soft tissue sarcoma. Well-differentiated liposarcoma can progress to dedifferentiated liposarcoma (DDLPS), a more aggressive form with higher metastatic potential and poor response to existing therapies. Progress in understanding and treating liposarcoma has been limited. To address this, we sought to develop an immunocompetent genetically engineered mouse model of liposarcoma. EXPERIMENTAL

designWe developed an autochthonous, immunocompetent liposarcoma mouse model [AAV8-Ap2.2-eGFP/Cre Ptenf/f;Trp53f/f C57BL/6 (ACPP)] by using targeted Cre-mediated deletion of Trp53 and Pten in adipocytes to mimic the signaling alterations observed in human liposarcoma. We characterized the histology, transcriptional features, and tumor microenvironment of this model. Additionally, we established syngeneic cell lines derived from ACPP DDLPS tumors and evaluated them for tumor formation, growth dynamics, and immune composition after implantation.

resultsACPP mice develop well-differentiated liposarcoma, DDLPS, and mixed tumors, mirroring human disease. Both murine and human DDLPS tumors share key transcriptional features and exhibit heterogeneous T-cell infiltration. Syngeneic DDLPS cell lines reliably form tumors in vivo, with each line demonstrating distinct growth kinetics, aggressiveness, and immune profiles.

conclusionsThe ACPP model provides a novel and clinically relevant platform to study liposarcoma in an immunocompetent setting. Along with the ACPP-derived cell lines, these models not only provide essential tools to understand the complex immunobiology of liposarcoma but also can be used to elucidate the underlying molecular mechanisms driving liposarcoma generation and progression and significantly accelerate the pace of preclinical studies aimed at uncovering more effective new therapies for patients with this aggressive malignancy.

Indexed as

LiposarcomaTumor MicroenvironmentAnimalsCell Line, TumorDisease Models, AnimalHumansImmunocompetenceMiceMice, Inbred C57BLPTEN PhosphohydrolaseTumor Suppressor Protein p53PTEN PhosphohydrolaseTrp53 protein, mouseTumor Suppressor Protein p53

Identifiers

PMID40928975
PMCPMC12664306

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.