Evidence map›Paper›PMID 41687610›Full record

ArticleCancer cell2026

Tumor-immune-neural circuit disrupts energy homeostasis in cancer cachexia.

Xiuhui Shi, Alex X Arreola, Zhijun Zhou, Jingxuan Yang, Mingyang Liu, Yang Cai, Yu Ren, Hao Yuan, Qun Chen, Xinjie Chen and 15 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 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

25 authors.

Xiuhui ShiDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Surgery, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Alex X ArreolaDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Pathology, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Zhijun ZhouDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Surgery, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Jingxuan YangDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Surgery, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Mingyang LiuDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Yang CaiDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Pathology, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Yu RenDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Hao YuanDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Qun ChenDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Xinjie ChenDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Xinyu YangDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Yimei MengDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Jingyi WangDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Wenyi LuoDepartment of Pathology, Yale School of Medicine, New Haven, CT 06519, USA.
Michael C RudolphDepartment of Biochemistry and Physiology, Harold Hamm Diabetes Center, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Rohan VarshneyDepartment of Biochemistry and Physiology, Harold Hamm Diabetes Center, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Kar-Ming FungDepartment of Pathology, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Chao XuDepartment of Biostatistics and Epidemiology, Hudson College of Public Health, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Wei R ChenStephenson School of Biomedical Engineering, The University of Oklahoma, Norman, OK 73019, USA.
Michael S BronzeDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Lei ZhengSidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX 78229, USA.
Yi-Ping LiDepartment of Integrative Biology & Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Courtney W HouchenDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA.
Yuqing ZhangDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA. Electronic address: yuqing-zhang@ou.edu.
Min LiDepartment of Medicine, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA; Department of Surgery, The University of Oklahoma Health Campus, Oklahoma City, OK 73104, USA. Electronic address: min-li@ou.edu.

Funding

Tissue Pathology Shared ResourceP30CA225520 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI ROBERT S. MANNEL · 2018 to 2026
$27.1M
Mentoring Translational Cancer Research in OklahomaP30GM154635 · NIGMS · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Rajagopal Ramesh · 2024 to 2026
$4.3M
Prognostic Biomarkers for ZIP4-mediated Cachexia in Pancreatic CancerR01CA203108 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LI, MIN, LI, YI-PING · 2016 to 2020
$2.7M
Potentiating a systemic antitumor response by interstitial localized ablative immunotherapy to synergize with immune checkpoint therapy for metastatic pancreatic tumorsR01CA269897 · NCI · UNIVERSITY OF OKLAHOMA · PI Wei R. Chen, MIN LI · 2022 to 2026
$2.5M
ZIP4 is a Novel Molecular Target in Human Pancreatic CancerR01CA186338 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FERNANDEZ-ZAPICO, MARTIN ERNESTO, LI, MIN · 2015 to 2019
$1.7M
Role of Zinc Dependent EMT-Transcription Factors (EMT-TF) in Pancreatic Cancer MetastasisR01CA247234 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI LI, MIN · 2020 to 2024
$1.6M
Axio SWhole slide scanning fluorescence and bright field microscopy with image analysis (ZEISScan.Z1)S10OD026744 · OD · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI FUNG, KAR-MING ARMIN · 2019 to 2019
$187k
Evaluating the role of the tumor macroenvironment in cancer cachexiaF99CA305566 · NCI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI Alex Arreola · 2025 to 2026
$87k
NCI NIH HHS F99 CA305566NCI NIH HHS P30 CA225520NCI NIH HHS R01 CA186338NCI NIH HHS R01 CA203108NCI NIH HHS R01 CA247234NCI NIH HHS R01 CA269897NIGMS NIH HHS P30 GM154635NIH HHS S10 OD026744
6 · The paper itself

Abstract

Cancer-induced cachexia and anorexia are debilitating complications across many cancers, yet effective treatments remain limited due to a poor understanding of the underlying mechanisms. Here, we identify an uncharacterized tumor-immune-neural circuit driving these syndromes, centered on growth and differentiation factor 15 (GDF15). Using genetically engineered mouse models, we find that loss of GDF15 protects against appetite loss, muscle wasting, and fat loss in pancreatic, lung, and skin cancers. Single-cell RNA sequencing reveals macrophages as a major source of GDF15, induced by tumor-derived colony-stimulating factor 1 (CSF1). GDF15 acts via the central nervous system to enhance β-adrenergic signaling in the tumor microenvironment, thereby amplifying cachexia. The disruption of this feedforward loop with GDF15-neutralizing antibody, anti-CSF1R antibody, or Rearranged during Transfection (RET) inhibitor markedly reduces both cachexia and anorexia. These findings reveal a non-cell-autonomous mechanism linking tumor signals, macrophage-derived GDF15, and neural pathways, highlighting the tumor-immune-neural triad as a promising therapeutic target.

Indexed as

CachexiaEnergy MetabolismGrowth Differentiation Factor 15NeoplasmsAnimalsAnorexiaHomeostasisHumansMacrophage Colony-Stimulating FactorMacrophagesMiceMice, KnockoutSignal TransductionTumor MicroenvironmentGdf15 protein, mouseGrowth Differentiation Factor 15Macrophage Colony-Stimulating Factoradipose lossbody compositionenergy expenditurehormonemetabolic stressmuscle atrophynorepinephrinesympathetic nervetumor-associated macrophagestumor immune microenvironment

Identifiers

PMID41687610
PMCPMC12959363

What OpenQuestion holds

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Read underepoch 390

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.