Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity

Nat Commun. 2020 Mar 20;11(1):1508. doi: 10.1038/s41467-020-15129-8.


Tumour cell phagocytosis by antigen presenting cells (APCs) is critical to the generation of antitumour immunity. However, cancer cells can evade phagocytosis by upregulating anti-phagocytosis molecule CD47. Here, we show that CD47 blockade alone is inefficient in stimulating glioma cell phagocytosis. However, combining CD47 blockade with temozolomide results in a significant pro-phagocytosis effect due to the latter's ability to induce endoplasmic reticulum stress response. Increased tumour cell phagocytosis subsequently enhances antigen cross-presentation and activation of cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in APCs, resulting in more efficient T cell priming. This bridging of innate and adaptive responses inhibits glioma growth, but also activates immune checkpoint. Sequential administration of an anti-PD1 antibody overcomes this potential adaptive resistance. Together, these findings reveal a dynamic relationship between innate and adaptive immune regulation in tumours and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity*
  • Animals
  • Antigen Presentation
  • Apoptosis
  • CD47 Antigen / drug effects
  • CD47 Antigen / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Models, Animal
  • Endoplasmic Reticulum / metabolism
  • Glioblastoma / immunology*
  • Glioblastoma / pathology
  • Glioma / immunology*
  • Humans
  • Immunity, Innate*
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred C57BL
  • Monitoring, Immunologic
  • Nucleotidyltransferases / metabolism
  • Phagocytosis / immunology*
  • T-Lymphocytes / immunology
  • Temozolomide / pharmacology


  • CD47 Antigen
  • CD47 protein, human
  • Nucleotidyltransferases
  • cGAS protein, human
  • Temozolomide