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<p>Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T cell lymphoma in women with textured implants. Little is known about the cell of origin (COO) and whether the tumour immune microenvironment (TIME) is critical for BIA-ALCL survival. Single-cell RNA sequencing revealed BIA-ALCL cells were heterogeneous with unique gene profiles per patient and signature genes BATF3, SERPINS, TNFSFR8, and IL2RA. The COO is a CD4<sup>+</sup> or CD8<sup>+</sup> memory T cell identified through rearranged TCR and gene expression. The BIA-ALCL TIME included distinct myeloid clusters, dendritic cells (DCs), and monocytes, which may support lymphoma cells. Cytokines IL-13, IL-10, TNF and secretory PDL1 were increased in BIA-ALCL seroma, indicating an immunosuppressive TIME. Interactome analysis revealed a complex network among lymphoma cells, dominated by IL-13, IL-10, and TNF members. Endogenous CD8<sup>+</sup> T cells exhibit higher checkpoint expression than benign seromas. No clonal relationship exists between BIA-ALCL and endogenous T cells. Tissue-archetype and gene-expression analysis revealed T-cell exclusion and immunosuppressive TIME in invasive disease. In summary, BIA-ALCL cells are diverse with markedly different TIME across stages. The TIME provides immunosuppressive signals to activated/exhausted T cells and homeostatic signals that promote BIA-ALCL proliferation. These new findings may offer novel therapeutic targets for advanced disease patients.</p>

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Breast implant associated anaplastic large cell lymphoma is a heterogeneous T cell disease with active pro-tumour cross-talk and immune suppression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月30日

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  • C. D’Souza,
  • Niko Thio,
  • Ruiqing Zhu,
  • Harini DeSilva,
  • Maria Mempin,
  • Luciano Martelotto,
  • Timothy Semple,
  • Ella Thompson,
  • Stephen Lade,
  • Mark Magnusson,
  • Nicholas Houseman,
  • Simon Overstall,
  • Heather Thorne,
  • Anand Deva,
  • Carrie van der Weyden,
  • Piers Blombery,
  • H. Miles Prince,
  • Paul J. Neeson

摘要

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare T cell lymphoma in women with textured implants. Little is known about the cell of origin (COO) and whether the tumour immune microenvironment (TIME) is critical for BIA-ALCL survival. Single-cell RNA sequencing revealed BIA-ALCL cells were heterogeneous with unique gene profiles per patient and signature genes BATF3, SERPINS, TNFSFR8, and IL2RA. The COO is a CD4+ or CD8+ memory T cell identified through rearranged TCR and gene expression. The BIA-ALCL TIME included distinct myeloid clusters, dendritic cells (DCs), and monocytes, which may support lymphoma cells. Cytokines IL-13, IL-10, TNF and secretory PDL1 were increased in BIA-ALCL seroma, indicating an immunosuppressive TIME. Interactome analysis revealed a complex network among lymphoma cells, dominated by IL-13, IL-10, and TNF members. Endogenous CD8+ T cells exhibit higher checkpoint expression than benign seromas. No clonal relationship exists between BIA-ALCL and endogenous T cells. Tissue-archetype and gene-expression analysis revealed T-cell exclusion and immunosuppressive TIME in invasive disease. In summary, BIA-ALCL cells are diverse with markedly different TIME across stages. The TIME provides immunosuppressive signals to activated/exhausted T cells and homeostatic signals that promote BIA-ALCL proliferation. These new findings may offer novel therapeutic targets for advanced disease patients.