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<p>Adrenocortical carcinomas (ACC) are aggressive and resistant to medical treatment. This study reports a single-nucleus transcriptome atlas of steroid and microenvironment cells in 38 human normal adrenals and adrenocortical tumors. We identify intermediate-state cells between glomerulosa and fasciculata, a transition state in the centripetal trans-differentiation of normal steroid cells. In tumors, steroid cells show expression programs reflecting this zonation. Although ACC microenvironment is scarce, its signatures combine with those of steroid cells into ecotypes. A first ecotype combines cancer-associated fibroblasts, tumor-associated endothelial cells, with hypoxia and mitosis signatures in steroid cells. Another ecotype combines exhausted T cells, with fasciculata steroid signature. These ecotypes are associated with poor survival. Conversely, a third ecotype combines inflammatory macrophages, with reticularis steroid signature, and better outcome. These steroid/microenvironment cells interplays improve outcome predictions and may open therapeutic options in aggressive ACC, through immune microenvironment activation by modulating glucocorticoids/androgens balance.</p>

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Impact of steroid differentiation on tumor microenvironment revealed by single-nucleus atlas of adrenal tumors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Anne Jouinot,
  • Yoann Martin,
  • Florian Violon,
  • Thomas Foulonneau,
  • Yanis Bendjelal,
  • Philip Calvet,
  • Brigitte Izac,
  • Franck Letourneur,
  • Céline Bertholle,
  • Muriel Andrieu,
  • Rachel Onifarasoaniaina,
  • Maryline Favier,
  • Charlène de Guitaut,
  • Archibald Fraikin,
  • Daniel de Murat,
  • Roberta Armignacco,
  • Nesrine Benanteur,
  • Maria Francesca Birtolo,
  • Mathilde Sibony,
  • Karine Perlemoine,
  • Patricia Vaduva,
  • Lucas Bouys,
  • Fidéline Bonnet-Serrano,
  • Bertrand Dousset,
  • Martin Gaillard,
  • Eric Pasmant,
  • Maxime Barat,
  • Anthony Dohan,
  • Magalie Haissaguerre,
  • Antoine Tabarin,
  • Rossella Libé,
  • Laurence Guignat,
  • Lionel Groussin,
  • Annabel Berthon,
  • Bruno Ragazzon,
  • Jérôme Bertherat,
  • Guillaume Assié

摘要

Adrenocortical carcinomas (ACC) are aggressive and resistant to medical treatment. This study reports a single-nucleus transcriptome atlas of steroid and microenvironment cells in 38 human normal adrenals and adrenocortical tumors. We identify intermediate-state cells between glomerulosa and fasciculata, a transition state in the centripetal trans-differentiation of normal steroid cells. In tumors, steroid cells show expression programs reflecting this zonation. Although ACC microenvironment is scarce, its signatures combine with those of steroid cells into ecotypes. A first ecotype combines cancer-associated fibroblasts, tumor-associated endothelial cells, with hypoxia and mitosis signatures in steroid cells. Another ecotype combines exhausted T cells, with fasciculata steroid signature. These ecotypes are associated with poor survival. Conversely, a third ecotype combines inflammatory macrophages, with reticularis steroid signature, and better outcome. These steroid/microenvironment cells interplays improve outcome predictions and may open therapeutic options in aggressive ACC, through immune microenvironment activation by modulating glucocorticoids/androgens balance.