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<p>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.</p>

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Differential assembly of mouse and human tumor microenvironments

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月19日

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  • Tristan Courau,
  • Rebecca G. Jaszczak,
  • Bushra Samad,
  • Emily Flynn,
  • Nayvin W. Chew,
  • Gabriella C. Reeder,
  • Jessica Tsui,
  • Semhar Teklu,
  • Lomax F. Pass,
  • Austin W. Edwards,
  • Mohammad Naser,
  • Arja Ray,
  • Harrison Wismer,
  • Daniel Bunis,
  • Leonard Lupin-Jimenez,
  • Noah V. Gavil,
  • David Masopust,
  • John P. Graham,
  • Daniel A. Skelly,
  • Xavier Vesco,
  • Edison T. Liu,
  • Gabriela K. Fragiadakis,
  • Alexis J. Combes,
  • Matthew F. Krummel

摘要

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.