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

Christina A. von Roemeling, Yifan Wang, Yaqing Qie, Hengfeng Yuan, Hai Zhao, Xiujie Liu, Zhaogang Yang, Mingming Yang, Weiye Deng, Katelyn A. Bruno, Charles K. Chan, Andrew S. Lee, Stephen S. Rosenfeld, Kyuson Yun, Aaron J. Johnson, Duane A. Mitchell, Wen Jiang, Betty Y.S. Kim

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article number1508
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    von Roemeling, C. A., Wang, Y., Qie, Y., Yuan, H., Zhao, H., Liu, X., Yang, Z., Yang, M., Deng, W., Bruno, K. A., Chan, C. K., Lee, A. S., Rosenfeld, S. S., Yun, K., Johnson, A. J., Mitchell, D. A., Jiang, W., & Kim, B. Y. S. (2020). Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity. Nature communications, 11(1), [1508]. https://doi.org/10.1038/s41467-020-15129-8