<p>Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. We use spatial transcriptomics and single-cell RNA sequencing to uncover distinct resistance programs in melanoma cells shaped by intrinsic cellular states and the tumor microenvironment. Consensus non-negative matrix factorization reveals shared intrinsic resistance programs across cell lines. In patient samples, these resistance programs coexist within individual tumors and associate with diverse immune signatures. Single-cell resolution spatial transcriptomics in xenograft models reveals both intrinsically determined and extrinsically influenced resistant fates. This work demonstrates that therapy-resistant fates coexist within distinct microenvironments and that tissue features influence which fate is adopted.</p>

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Spatial transcriptomics reveals influence of microenvironment on intrinsic fates in melanoma therapy resistance

  • Ryan H. Boe,
  • Catherine G. Triandafillou,
  • Rossana Lazcano,
  • Jennifer A. Wargo,
  • Arjun Raj

摘要

Resistance to cancer therapy is driven by both cell-intrinsic and microenvironmental factors. We use spatial transcriptomics and single-cell RNA sequencing to uncover distinct resistance programs in melanoma cells shaped by intrinsic cellular states and the tumor microenvironment. Consensus non-negative matrix factorization reveals shared intrinsic resistance programs across cell lines. In patient samples, these resistance programs coexist within individual tumors and associate with diverse immune signatures. Single-cell resolution spatial transcriptomics in xenograft models reveals both intrinsically determined and extrinsically influenced resistant fates. This work demonstrates that therapy-resistant fates coexist within distinct microenvironments and that tissue features influence which fate is adopted.