Nicola Aceto


Last Name

Aceto

First Name

Nicola

ORCID

0000-0001-9579-6918

Organisational unit

09736 - Aceto, Nicola / Aceto, Nicola

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2024 - 20254
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Publications 1 - 4 of 4
  • A Molecular Voyage: Multi-Omics Insights into Circulating Tumor Cells
    Item type: Review Article
    Zhang, Yu Wei; Gvozdenovic, Ana; Aceto, Nicola (2024)
    Cancer Discovery
    Circulating tumor cells (CTCs) play a pivotal role in metastasis, the leading cause of cancer-associated death. Recent improvements of CTC isolation tools, coupled with a steady development of multiomics technologies at single-cell resolution, have enabled an extensive exploration of CTC biology, unlocking insights into their molecular profiles. A detailed molecular portrait requires CTC interrogation across various levels encompassing genomic, epigenetic, transcriptomic, proteomic and metabolic features. Here, we review how state-of-the-art multiomics applied to CTCs are shedding light on how cancer spreads. Further, we highlight the potential implications of CTC profiling for clinical applications aimed at enhancing cancer diagnosis and treatment.Significance: Exploring the complexity of cancer progression through cutting-edge multiomics studies holds the promise of uncovering novel aspects of cancer biology and identifying therapeutic vulnerabilities to suppress metastasis.
  • PDL1-expressing macrophages infiltrate diffuse large B-cell lymphoma and promote lymphoma growth in a MYC-driven experimental model
    Item type: Journal Article
    Cui, Ningxuan; Leary, Peter; Ivanova, Vanesa-Sindi; et al. (2025)
    Blood Cancer Journal
    The infiltration of diffuse large- and other mature B-cell lymphomas with T- and myeloid cells is a key tumor microenvironmental feature but is not currently factored into treatment decisions. Here, we have used multiplex immunofluorescence microscopy to quantify the immune infiltrates of >260 diffuse large B-cell- (DLBCL), follicular- (FL) and mantle cell lymphomas (MCL), and chronic lymphocytic leukemias (CLL) relative to clinical outcomes, mutational landscape and phenotype. MCL were found to be the "coldest" and DLBCL the "hottest" entities. The lymphoma microenvironment of DLBCL featured numerically dominant populations of CD8(+) and T-follicular helper (Tfh) T-cells that were indicative of superior prognosis. Mutations in EZH2, PTEN and KMT2D were overrepresented in DLBCL with low CD8(+) T-cell infiltration. A unique feature of DLBCL was its infiltration by large numbers of PDL1(+) macrophages that constituted up to 70% of total cellularity. PDL1(+) macrophage infiltration was mutually exclusive with regulatory T-cell infiltration. The inducible ablation of PDL1 on macrophages was sufficient to improve immune control of MYC-expressing lymphoma in a syngeneic immunocompetent model. These results implicate the macrophage/CD8(+) T-cell axis as a key pathogenetic determinant and immunotherapeutic target in a subset of DLBCL patients with poor prognosis.
  • Phylogenetic inference reveals clonal heterogeneity in circulating tumor cell clusters
    Item type: Journal Article
    Gremmelspacher, David; Gawron, Johannes; Szczerba, Barbara M.; et al. (2025)
    Nature Genetics
    Circulating tumor cell (CTC) clusters are highly efficient metastatic seeds in various cancers. Yet, their genetic heterogeneity and clonal architecture is poorly characterized. Using whole-exome sequencing coupled with phylogenetic inference from CTC clusters of patients with breast and prostate cancer, as well as mouse cancer models alongside barcode-mediated clonal tracking in vivo, we demonstrate oligoclonal composition of individual CTC clusters. These results improve our understanding of metastasis-relevant clonal dynamics.
  • MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation
    Item type: Journal Article
    Cangkrama, Michael; Liu, Huan; Wu, Xiaoyu; et al. (2025)
    Nature Cancer
    Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment that commonly support cancer development and progression. Here we show that different cancer cells transfer mitochondria to fibroblasts in cocultures and xenograft tumors, thereby inducing protumorigenic CAF features. Transplantation of functional mitochondria from cancer cells induces metabolic alterations in fibroblasts, expression of CAF markers and release of a protumorigenic secretome and matrisome. These features promote tumor formation in preclinical mouse models. Mechanistically, the mitochondrial transfer requires the mitochondrial trafficking protein MIRO2. Its depletion in cancer cells suppresses mitochondrial transfer and inhibits CAF differentiation and tumor growth. The clinical relevance of these findings is reflected by the overexpression of MIRO2 in tumor cells at the leading edge of epithelial skin cancers. These results identify mitochondrial transfer from cancer cells to fibroblasts as a driver of tumorigenesis and provide a rationale for targeting MIRO2 and mitochondrial transfer in different malignancies.
Publications 1 - 4 of 4