2026
Differential assembly of mouse and human tumor microenvironments
Courau T, Jaszczak RG, Samad B, Flynn E, Chew NW, Reeder GC, Tsui J, Teklu S, Pass LF, Edwards AW, Naser M, Ray A, Wismer H, Bunis D, Lupin-Jimenez L, Gavil NV, Masopust D, Graham JP, Skelly DA, Vesco X, Liu ET, Fragiadakis GK, Combes AJ, Krummel MF.
Show affiliations
- Courau T — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA. tristan.courau@ucsf.edu.
- Jaszczak RG — CoLabs, UCSF, San Francisco, CA, USA.
- Samad B — ImmunoProfiler Initiative, UCSF, San Francisco, CA, USA.
- Flynn E — CoLabs, UCSF, San Francisco, CA, USA.
- Chew NW — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Reeder GC — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Tsui J — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Teklu S — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Pass LF — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Edwards AW — CoLabs, UCSF, San Francisco, CA, USA.
- Naser M — CoLabs, UCSF, San Francisco, CA, USA.
- Ray A — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Wismer H — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Bunis D — CoLabs, UCSF, San Francisco, CA, USA.
- Lupin-Jimenez L — CoLabs, UCSF, San Francisco, CA, USA.
- Gavil NV — Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
- Masopust D — Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN, USA.
- Graham JP — The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
- Skelly DA — The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
- Vesco X — The Jackson Laboratory for Mammalian Genetics, Bar Harbor, ME, USA.
- Liu ET — The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
- Fragiadakis GK — CoLabs, UCSF, San Francisco, CA, USA.
- Combes AJ — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA.
- Krummel MF — Department of Pathology and ImmunoX Initiative, UCSF, San Francisco, CA, USA. max.krummel@ucsf.edu.
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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the paper seems to compare tumor too broadly and defines mouse tumors as not T cell infiltrated even though they are? the exact bioinformatic pipeline is not clear to me and even though the question they are trying to ask is a very valid one I am not convinced about their methodology.