2025 Hyper Recent •CC0 1.0 Universal

This work is dedicated to the public domain. No rights reserved.

Access Preprint From Server
July 1st, 2025
Version: 3
University of Vermont College of Medicine
cancer biology
biorxiv

Early adipose tissue wasting in a novel preclinical model of human lung cancer cachexia

Snoke, D. B.Open in Google Scholar•van der Velden, J. L.Open in Google Scholar•Bellefleur, E. R.Open in Google Scholar•Dearborn, J. S.Open in Google Scholar•Lenahan, S. M.Open in Google Scholar•Beal, A. E.Open in Google Scholar•Aboushousha, R.Open in Google Scholar•Heininger, S. C. J.Open in Google Scholar•Ather, J. L.Open in Google Scholar•Mank, M. M.Open in Google Scholaret al.

Cancer cachexia (CC), a syndrome of skeletal muscle and adipose wasting, reduces responsiveness to therapies and increases mortality. There are no approved treatments for CC, which may relate to discordance between pre-clinical models and human CC. To address the need for clinically relevant models of lung CC, we generated inducible, lung epithelial cell specific KrasG12D/+ (G12D) mice. G12D mice develop CC over a protracted time course and phenocopy tissue and tumor, cellular, mutational, transcriptomic, and metabolic characteristics of human lung CC. G12D mice demonstrate early loss of adipose, a phenotype that was apparent across numerous models of CC and translates to patients with lung cancer. Tumor-released factors promote adipocyte lipolysis, a driver of adipose wasting in CC, and adipose wasting was inversely related to tumor burden. Thus, G12D mice model key features of human lung CC and highlight a role for early tumor metabolic reprogramming of adipose tissue in CC.

Similar Papers

biorxiv
Tue Jul 01 2025
KDM5 demethylases suppress R-loop-mediated viral mimicry and DNA damage in breast cancer cells
Tumors with low expression of Interferon-Stimulated Genes (ISG) and Antigen Presentation (AP) genes respond relatively poorly to current immunotherapies. One of the early hallmarks of cancer is DNA hypomethylation in genomic repeat regions, resulting in the expression of normally silenced endogenous viral elements. Such epigenetic changes have the potential to augment anti-tumor immune responses a...
Lau, L.
•
Henderson, K.
•
Turkoz, A.
•
Linker, S.
...•
Classon, M.
biorxiv
Tue Jul 01 2025
CD300e is a driver of the immunosuppressive tumor microenvironment and colorectal cancer progression via macrophage reprogramming
Colorectal cancer (CRC) progression is shaped by the tumor microenvironment, particularly tumor-associated macrophages (TAMs), which often adopt immunosuppressive functions. CD300e, a myeloid receptor involved in immune regulation, has an uncharacterized role in CRC. Here, we show that CD300e is selectively upregulated in tumor-infiltrating monocytes and macrophages, driving a suppressive phenotyp...
Barizza, A.
•
Vassallo, S.
•
Masatti, L.
•
Laffranchi, M.
...•
Codolo, G.
biorxiv
Tue Jul 01 2025
Inferring cell dynamics in stress-induced neuroblastoma cell cultures
Neuroblastoma is characterised by significant intratumoural heterogeneity which complicates treatments. Phenotypic plasticity, i.e., the ability of cells to alter their phenotype without genetic mutations, is a key factor contributing to this heterogeneity. In this study, we quantify cell actions and cell-to-cell interactions that lead to phenotypic adaptation in vitro under stress, specifically l...
Hafiichuk, K.
•
Hamis, S.
•
Karlsson, J.
•
Gisselsson, D.
•
Chattopadhyay, S.
biorxiv
Tue Jul 01 2025
Sweet taste receptor regulates proliferation and glucose uptake in glioblastoma cells
Glioblastoma is a brain tumour classified by the World Health Organization as grade 4 due to its aggressiveness, invasiveness, and poor differentiation. Current standard therapies remain largely ineffective, reinforcing the need for novel targets to improve glioblastoma prognosis. Reprogramming of cellular metabolism is an important hallmark of cancer, marked by a shift from oxidative phosphorylat...
Costa, A. R.
•
Duarte, A. C.
•
Jorge, A. C.
•
Goncalves, I.
...•
Santos, C. R. A.
biorxiv
Mon Jun 30 2025
CD47 blockade enhances immunoradiotherapy response in head and neck squamous cell carcinoma
Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide, with limited treatment options for patients with locally advanced disease. CD47 immune checkpoint inhibitors have been used to block the CD47/SIRPa interaction that inhibits antigen-presenting cell phagocytosis, thereby enhancing antigen presentation to cytotoxic T-cells, and have shown promi...
Monther, A.
•
Al-Msari, R.
•
Saddawi-Konefka, R.
•
Fassardi, S.
...•
Califano, J.
biorxiv
Mon Jun 30 2025
Intratumoral Treg ablation is sufficient to mediate tumor control systemically without autoimmunity
Regulatory T cells (Tregs) infiltrate most tumors, yet whether they suppress immune responses directly within tumor tissues is untested. We used intratumoral (IT) delivery of diphtheria toxin (DT) in Foxp3DTR mice to deplete IT Tregs while leaving peripheral Tregs intact. IT delivery of DT reduced Treg frequencies in the tumor, which promoted potent tumor control without autoimmunity. Interestingl...
Bockman, A.
•
Gittins, B.
•
Zhang, C.
•
Hung, J.
...•
DuPage, M.
biorxiv
Mon Jun 30 2025
Pan-cancer prediction of tumor immune activation and response to immune checkpoint blockade from tumor transcriptomics and histopathology
Accurately predicting which patients will respond to immune checkpoint blockade (ICB) remains a major challenge. Here, we present TIME_ACT, an unsupervised 66-gene transcriptomic signature of tumor immune activation derived from TCGA melanoma data. First, TIME_ACT scores accurately identify tumors with activated immune microenvironments across cancer types. Analysis of spatial features of the tumo...
Mukherjee, S.
•
Patiyal, S.
•
Pal, L. R.
•
Chang, T.
...•
Ruppin, E.
biorxiv
Mon Jun 30 2025
Reprogramming of Osimertinib-Resistant EGFR-mutant NSCLC: The Pyruvate-Acetaldehyde-Acetate Pathway As a Key Driver of Resistance
Osimertinib (Osi) resistance remains a significant challenge in EGFR mutant non-small-cell lung cancer (NSCLC). This study investigates the metabolic reprogramming associated with Osi resistance, identifying key metabolic vulnerabilities that may be targeted for therapeutic intervention. Employing the EGFR-mutant H1975 parental (Par) cell line and its Osi-resistant (OsiR) counterpart, we integrate...
Maroni, G.
•
Cabrera San Millan, E.
•
Mercatelli, R.
•
Chiodi, A.
...•
Levantini, E.
biorxiv
Mon Jun 30 2025
Targeting breast cancer senescence in 3D models of bone metastasis
Chemotherapeutic treatment of breast cancer with Doxorubicin can induce tumor and stromal cell senescence leading to therapy-resistance. Senescence-associated secretory phenotype (SASP) promotes secretion of pro-inflammatory and tumorigenic factors causing systemic inflammation. Combined, this can result in immune suppression, tumor growth and secondary spread of cancer. Targeting and removing sen...
Hamburger, E. C. B.
•
Mohseni Garakani, M.
•
Alfaisali, S.
•
Ouellet, J. A.
...•
Rosenzweig, D. H.