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

First Author  von Roemeling CA Year  2020
Journal  Nat Commun Volume  11
Issue  1 Pages  1508
PubMed ID  32198351 Mgi Jnum  J:286385
Mgi Id  MGI:6401571 Doi  10.1038/s41467-020-15129-8
Citation  von Roemeling CA, et al. (2020) Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity. Nat Commun 11(1):1508
abstractText  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.
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