Breast implant associated anaplastic large cell lymphoma is a heterogeneous T cell disease with active pro-tumour cross-talk and immune suppression
- Author(s)
- D'Souza, C; Thio, N; Zhu, R; DeSilva, H; Mempin, M; Martelotto, L; Semple, T; Thompson, E; Lade, S; Magnusson, M; Houseman, N; Overstall, S; Thorne, H; Deva, A; van der Weyden, C; Blombery, P; Prince, HM; Neeson, PJ;
- Journal Title
- Leukemia
- Publication Type
- Online publication before print
- Abstract
- 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.
- Department(s)
- Laboratory Research; Pathology; Medical Oncology
- Publisher's Version
- https://doi.org/10.1038/s41375-026-03049-3
- Open Access at Publisher's Site
https://doi.org/10.1038/s41375-026-03049-3- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2026-08-11 02:01:22
Last Modified: 2026-08-11 02:01:47