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Single-cell RNA sequencing reveals pro-tumorigenic intestinal mast cell programs in colorectal cancer

Nature作者：Erisa Putro2026年8月12日正文已收录本站
  • Article
  • Open access
  • Published:
  • Alessia Carnevale  ORCID: orcid.org/0009-0009-4961-51301,
  • Caterina Marangio1,
  • Giuseppe Pietropaolo2,
  • Nadia Domenica Milito1,
  • Giovanna Peruzzi  ORCID: orcid.org/0000-0002-6517-91073,
  • Cinzia Fionda1,
  • Helena Stabile1,
  • Francesca Sozio1,
  • Angela Santoni1,2,
  • Giuseppe Sciumè  ORCID: orcid.org/0000-0003-0131-512X1,
  • Valerio Fulci1,
  • Rosa Molfetta  ORCID: orcid.org/0000-0003-2904-63711 na1 &
  • …
  • Rossella Paolini  ORCID: orcid.org/0000-0001-7605-15311 na1 

Cell Death & Disease (2026) Cite this article

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Abstract

Mast cells (MCs) are multifunctional immune cells with context-dependent functions in cancer. In colorectal cancer (CRC), their contribution remains debated, suggesting that distinct MC subsets may either support tumor progression or promote anti-tumor immunity. Using single-cell RNA sequencing in a mouse model of inflammation-driven CRC, we uncovered extensive MC plasticity during tumor progression. Transcriptomic profiling and pseudotime trajectory analysis revealed a transition from precursor-like MCs exclusively present in adjacent tissue to differentiated tumor-associated MC (TAMC) subsets. TAMCs displayed a distinct repertoire of proteases and pro-inflammatory cytokines, contributing to increased vascular permeability and recruitment of additional immune cells. Moreover, TAMCs exhibited upregulation of molecules with immunosuppressive potential and underwent a tumor microenvironment (TME)-driven metabolic reprogramming. Accordingly, antibody-mediated MC depletion reduced tumor burden. Notably, most of the transcriptional features identified in a murine CRC model were recapitulated in human CRC, supporting the translational relevance of this MC program. Our findings identify a tumor-adapted MC state that orchestrates immune evasion and tissue remodeling during CRC progression, supporting the notion that MC are reprogrammed toward an immune-suppressive and pro-tumorigenic phenotype.

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Funding

This work was supported by grants from the Italian Association for Cancer Research (AIRC IG 24955-P.I.: Paolini Rossella; AIRC IG 28719-P.I.: Giuseppe Sciumè; 5×1000-21147-P.I.: Angela Santoni) and the Istituto Pasteur Italia-Fondazione Cenci Bolognetti (2020-366). GiuP received a salary from PNRR-MAD-2022-12375947, Next Generation EU - PNRR M6C2 - Investimento 2.1 Valorizzazione e potenziamento della ricerca biomedica del SSN.

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Author notes

  1. Erisa Putro

    Present address: Department of Molecular and Clinical Medicine, Sapienza University of Rome, Rome, Italy

  2. These authors contributed equally: Rosa Molfetta, Rossella Paolini.

Authors and Affiliations

  1. Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur Italia - Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy

    Erisa Putro, Alessia Carnevale, Caterina Marangio, Nadia Domenica Milito, Cinzia Fionda, Helena Stabile, Francesca Sozio, Angela Santoni, Giuseppe Sciumè, Valerio Fulci, Rosa Molfetta & Rossella Paolini

  2. IRCCS Neuromed, Pozzilli, Italy

    Giuseppe Pietropaolo & Angela Santoni

  3. Center for Life Nano & Neuro Science, Istituto Italiano di Tecnologia, Rome, Italy

    Giovanna Peruzzi

Authors

  1. Erisa Putro
  2. Alessia Carnevale
  3. Caterina Marangio
  4. Giuseppe Pietropaolo
  5. Nadia Domenica Milito
  6. Giovanna Peruzzi
  7. Cinzia Fionda
  8. Helena Stabile
  9. Francesca Sozio
  10. Angela Santoni
  11. Giuseppe Sciumè
  12. Valerio Fulci
  13. Rosa Molfetta
  14. Rossella Paolini

Corresponding authors

Correspondence to Erisa Putro or Rossella Paolini.

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Competing interests

The authors declare no competing interests.

Ethics

All animal studies were conducted in accordance with all relevant ethical regulations for animal testing and research, including the Italian code for the care and use of animals for scientific purposes (Authorization no. 698/2021-PR).

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Edited by Dr Gerry Melino

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Putro, E., Carnevale, A., Marangio, C. et al. Single-cell RNA sequencing reveals pro-tumorigenic intestinal mast cell programs in colorectal cancer. Cell Death Dis (2026). https://doi.org/10.1038/s41419-026-09183-1

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  • DOI: https://doi.org/10.1038/s41419-026-09183-1