IRCCS Humanitas Research Hospital & Humanitas University
Published January 21, 2022 | Version v1
Dataset Open

Dataset related to article "Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression"

Authors/Creators

  • 1. IRCCS Humanitas Research Hospital, via Manzoni 56, 20072 Rozzano (Mi) - Italy
  • 2. Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele – Milan, Italy
  • 3. The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ
  • 4. IRCCS Humanitas Research Hospital, via Manzoni 56,20089 Rozzano (Mi) - Italy AND Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele – Milan, Italy
  • 5. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA 17 19104, USA.
  • 6. IRCCS Humanitas Research Hospital, via Manzoni 56, 20072 Rozzano (Mi) - Italy AND Institute of Genetic and Biomedical Research, UoS Milan, National Research Council, Rozzano, Milan, Italy.
  • 7. IRCCS Humanitas Research Hospital, via Manzoni 56,20089 Rozzano (Mi) - Italy AND Humanitas University, Department of Biomedical Sciences, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele – Milan, Italy AND The William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ.

Description

This record contains raw data related to article “Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression"

Complement has emerged as a component of tumor promoting inflammation. We conducted a systematic assessment of the role of complement activation and effector pathways in sarcomas. C3 -/-, MBL1/2 -/- and C4 -/- mice showed reduced susceptibility to 3-methylcholanthrene sarcomagenesis and transplanted sarcomas, whereas C1q and factor B deficiency had marginal effects. Complement 3a receptor (C3aR), but not C5aR1 and C5aR2, deficiency mirrored the phenotype of C3 -/- mice. C3 and C3aR deficiency were associated with reduced accumulation and functional skewing of tumor-associated macrophages, increased T cell activation and response to anti-PD-1 therapy. Transcriptional profiling of sarcoma infiltrating macrophages and monocytes revealed the enrichment of MHC II-dependent antigen presentation pathway in C3-deficient cells. In patients, C3aR expression correlated with a macrophage population signature and C3 deficiency-associated signatures predicted better clinical outcome. These results suggest that the lectin pathway and C3a/C3aR axis are key components of complement and macrophage-mediated sarcoma promotion and immunosuppression.

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Additional details

Related works

Is supplement to
34505065 (PMID)
10.1038/s43018-021-00173-0 (DOI)