Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity.
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| 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.
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| Authors | 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 |
| Journal | Nature communications (Nat Commun) Vol. 11 Issue 1 Pg. 1508 (03 20 2020) ISSN: 2041-1723 [Electronic] England |
| PMID | 32198351 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.) |
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