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Tissue-resident glial cells associate with tumoral vasculature and promote cancer progression

  • Beatriz G.S. Rocha
  • , Caroline C. Picoli
  • , Bryan O.P. Gonçalves
  • , Walison N. Silva
  • , Alinne C. Costa
  • , Michele M. Moraes
  • , Pedro A.C. Costa
  • , Gabryella S.P. Santos
  • , Milla R. Almeida
  • , Luciana M. Silva
  • , Youvika Singh
  • , Marcelo Falchetti
  • , Gabriela D.A. Guardia
  • , Pedro P.G. Guimarães
  • , Remo C. Russo
  • , Rodrigo R. Resende
  • , Mauro C C.X. Pinto
  • , Jaime H. Amorim
  • , Vasco A.C. Azevedo
  • , Alexandre Kanashiro
  • Helder I. Nakaya, Edroaldo L. Rocha, Pedro A.F. Galante, Akiva Mintz, Paul S. Frenette, Alexander Birbrair

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Cancer cells are embedded within the tissue and interact dynamically with its components during cancer progression. Understanding the contribution of cellular components within the tumor microenvironment is crucial for the success of therapeutic applications. Here, we reveal the presence of perivascular GFAP+/Plp1+ cells within the tumor microenvironment. Using in vivo inducible Cre/loxP mediated systems, we demonstrated that these cells derive from tissue-resident Schwann cells. Genetic ablation of endogenous Schwann cells slowed down tumor growth and angiogenesis. Schwann cell-specific depletion also induced a boost in the immune surveillance by increasing tumor-infiltrating anti-tumor lymphocytes, while reducing immune-suppressor cells. In humans, a retrospective in silico analysis of tumor biopsies revealed that increased expression of Schwann cell-related genes within melanoma was associated with improved survival. Collectively, our study suggests that Schwann cells regulate tumor progression, indicating that manipulation of Schwann cells may provide a valuable tool to improve cancer patients’ outcomes.

Original languageEnglish
Pages (from-to)129-166
Number of pages38
JournalAngiogenesis
Volume26
Issue number1
DOIs
StatePublished - Feb 2023
Externally publishedYes

Keywords

  • Genetic depletion
  • Glia
  • Perivascular cells
  • Tumor microenvironment

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