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Peer-reviewedCC BYNature Immunology

Differential assembly of mouse and human tumor microenvironments

  • Tristan Courau1,2,3,4,5
  • Rebecca Garrett Jaszczak6,5
  • Bushra Samad6,7,5,8
  • Emily Flynn6,5
  • Nayvin W. Chew6,9,7,5,8
  • Gabriella C. Reeder6,9,7,5,8
  • Jessica L. Tsui6,9,7,4,5
  • Semhar Teklu9,7,4
  • Lomax F. Pass9,7,4,5
  • Austin W. Edwards6,5
  • Mohammad Naser6,5
  • Arja Ray9,7,10
12 more authors
  • Harrison Wismer6,9,7,10
  • Daniel G. Bunis6,11
  • Leonard C. Lupin-Jimenez6,11
  • Noah Veis Gavil10,11
  • David Masopust10,12
  • John P. Graham11,13,5
  • Daniel A. Skelly11,14,4
  • Xavier Vesco11,4
  • Edison T. Liu15
  • Gabriela K. Fragiadakis6,16
  • Alexis J. Combes6,17,9,7
  • Matthew F. Krummel18,19
19 affiliations
  1. 1CoLabs, UCSF, San Francisco, CA, USA. [email protected]
  2. 2Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA. [email protected]
  3. 3ImmunoProfiler Initiative, UCSF, San Francisco, CA, USA. [email protected]
  4. 4Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA 9443, USA
  5. 5UCSF CoLabs
  6. 6CoLabs, UCSF, San Francisco, CA, USA
  7. 7ImmunoProfiler Initiative, UCSF, San Francisco, CA, USA
  8. 8UCSF ImmunoProfiler Initiative
  9. 9Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA
  10. 10Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA
  11. 11The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA
  12. 12The Jackson Laboratory for Genomic Medicine, Farmington, CT, US
  13. 13Department of Medicine, Division of Rheumatology, UCSF
  14. 14Department of Medicine, Division of Gastroenterology, UCSF
  15. 15The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA
  16. 16Department of Medicine, Division of Rheumatology, UCSF, San Francisco, CA, USA
  17. 17Department of Medicine, Division of Gastroenterology, UCSF, San Francisco, CA, USA
  18. 18Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA. [email protected]
  19. 19ImmunoProfiler Initiative, UCSF, San Francisco, CA, USA. [email protected]
Open at sourceDOICite

Abstract

Mouse models are frequently used to develop treatments for human cancer. However, the degree to which their tumor microenvironments (TMEs) are synonymously assembled is particularly poorly characterized. Through systematic immunoprofiling of 15 commonly used mouse models, we found that most murine TMEs recapitulate the composition of poorly infiltrated human tumors, extensively biased toward high macrophage densities. We discovered substantial species-specific biases of chemokine expression networks known to drive TMEs assembly, together with discoordinated frequencies of T and myeloid cell subtypes. Even with variable alignment, conserved cell-type-specific gene expression programs emerged across species and cohorts. Dissecting the coordinated T cell-myeloid gene expression programs revealed a conserved axis between interferon-responsive myeloid states and ongoing T cell cytotoxicity that transcends tissue of origin and predicts clinical outcome. Collectively, this work provides a practical atlas outlining both the hazards and opportunities of using mice to model human cancer.

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Cite

BibTeXRIS
BibTeX
@article{courau2026differential,
  title = {{Differential assembly of mouse and human tumor microenvironments}},
  author = {Tristan Courau and Rebecca Garrett Jaszczak and Bushra Samad and Emily Flynn and Nayvin W. Chew and Gabriella C. Reeder and Jessica L. Tsui and Semhar Teklu and Lomax F. Pass and Austin W. Edwards and Mohammad Naser and Arja Ray and Harrison Wismer and Daniel G. Bunis and Leonard C. Lupin-Jimenez and Noah Veis Gavil and David Masopust and John P. Graham and Daniel A. Skelly and Xavier Vesco and Edison T. Liu and Gabriela K. Fragiadakis and Alexis J. Combes and Matthew F. Krummel},
  journal = {Nature Immunology},
  year = {2026},
  month = may,
  doi = {10.1038/s41590-026-02505-7},
  url = {https://doi.org/10.1038/s41590-026-02505-7},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Differential assembly of mouse and human tumor microenvironments
AU  - Tristan Courau
AU  - Rebecca Garrett Jaszczak
AU  - Bushra Samad
AU  - Emily Flynn
AU  - Nayvin W. Chew
AU  - Gabriella C. Reeder
AU  - Jessica L. Tsui
AU  - Semhar Teklu
AU  - Lomax F. Pass
AU  - Austin W. Edwards
AU  - Mohammad Naser
AU  - Arja Ray
AU  - Harrison Wismer
AU  - Daniel G. Bunis
AU  - Leonard C. Lupin-Jimenez
AU  - Noah Veis Gavil
AU  - David Masopust
AU  - John P. Graham
AU  - Daniel A. Skelly
AU  - Xavier Vesco
AU  - Edison T. Liu
AU  - Gabriela K. Fragiadakis
AU  - Alexis J. Combes
AU  - Matthew F. Krummel
PY  - 2026
DA  - 2026/05/19
JO  - Nature Immunology
DO  - 10.1038/s41590-026-02505-7
UR  - https://doi.org/10.1038/s41590-026-02505-7
AB  - Mouse models are frequently used to develop treatments for human cancer. However, the degree to which their tumor microenvironments (TMEs) are synonymously assembled is particularly poorly characterized. Through systematic immunoprofiling of 15 commonly used mouse models, we found that most murine TMEs recapitulate the composition of poorly infiltrated human tumors, extensively biased toward high macrophage densities. We discovered substantial species-specific biases of chemokine expression networks known to drive TMEs assembly, together with discoordinated frequencies of T and myeloid cell subtypes. Even with variable alignment, conserved cell-type-specific gene expression programs emerged across species and cohorts. Dissecting the coordinated T cell-myeloid gene expression programs revealed a conserved axis between interferon-responsive myeloid states and ongoing T cell cytotoxicity that transcends tissue of origin and predicts clinical outcome. Collectively, this work provides a practical atlas outlining both the hazards and opportunities of using mice to model human cancer.
SN  - 1529-2908
SN  - 1529-2916
ER  -