Glioblastoma ablates pericytes antitumor immune function through aberrant up-regulation of chaperone-mediated autophagy

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Abstract
Significance: Glioblastoma (GB) is the most lethal brain malignancy without an effective treatment. In this study, we demonstrate that tumor-induced change in chaperone-mediated autophagy (CMA) in host perivascular cells is a targetable process to prevent GB progression. CMA regulates pericyte interaction with tumor cells and sustains the acquired immunosuppressive function of pericytes, which is required for tumor survival. Blockage of CMA results in changes in the protein levels involved in cell-to-cell interaction and affects the pericyte secretory phenotype, resulting in defective GB adhesion and diminished tumor survival. This work reveals a previously unknown capacity of GB to modulate host pericyte CMA to assist in its own progression. Our results highlight the possibility of targeting CMA to treat this aggressive disease.
Funding Information
  • Ministerio de Economía y Competitividad (SAF2015-73923-JIN)
  • Fundación Séneca (19667/EE/14)
  • Fundación Séneca (20840/PI/18)
  • MINECO | Instituto de Salud Carlos III (RD16/0011/0010)
  • MINECO | Instituto de Salud Carlos III (RD16/0011/0001)
  • HHS | NIH | National Institute on Aging (P01 AG031782)

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