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

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 phagocytosi...

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Autores principales: von Roemeling, Christina A., Wang, Yifan, Qie, Yaqing, Yuan, Hengfeng, Zhao, Hai, Liu, Xiujie, Yang, Zhaogang, Yang, Mingming, Deng, Weiye, Bruno, Katelyn A., Chan, Charles K., Lee, Andrew S., Rosenfeld, Stephen S., Yun, Kyuson, Johnson, Aaron J., Mitchell, Duane A., Jiang, Wen, Kim, Betty Y. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083893/
https://www.ncbi.nlm.nih.gov/pubmed/32198351
http://dx.doi.org/10.1038/s41467-020-15129-8
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author von Roemeling, Christina A.
Wang, Yifan
Qie, Yaqing
Yuan, Hengfeng
Zhao, Hai
Liu, Xiujie
Yang, Zhaogang
Yang, Mingming
Deng, Weiye
Bruno, Katelyn A.
Chan, Charles K.
Lee, Andrew S.
Rosenfeld, Stephen S.
Yun, Kyuson
Johnson, Aaron J.
Mitchell, Duane A.
Jiang, Wen
Kim, Betty Y. S.
author_facet von Roemeling, Christina A.
Wang, Yifan
Qie, Yaqing
Yuan, Hengfeng
Zhao, Hai
Liu, Xiujie
Yang, Zhaogang
Yang, Mingming
Deng, Weiye
Bruno, Katelyn A.
Chan, Charles K.
Lee, Andrew S.
Rosenfeld, Stephen S.
Yun, Kyuson
Johnson, Aaron J.
Mitchell, Duane A.
Jiang, Wen
Kim, Betty Y. S.
author_sort von Roemeling, Christina A.
collection PubMed
description 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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spelling pubmed-70838932020-03-23 Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity von Roemeling, Christina A. Wang, Yifan Qie, Yaqing Yuan, Hengfeng Zhao, Hai Liu, Xiujie Yang, Zhaogang Yang, Mingming Deng, Weiye Bruno, Katelyn A. Chan, Charles K. Lee, Andrew S. Rosenfeld, Stephen S. Yun, Kyuson Johnson, Aaron J. Mitchell, Duane A. Jiang, Wen Kim, Betty Y. S. Nat Commun Article 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. Nature Publishing Group UK 2020-03-20 /pmc/articles/PMC7083893/ /pubmed/32198351 http://dx.doi.org/10.1038/s41467-020-15129-8 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
von Roemeling, Christina A.
Wang, Yifan
Qie, Yaqing
Yuan, Hengfeng
Zhao, Hai
Liu, Xiujie
Yang, Zhaogang
Yang, Mingming
Deng, Weiye
Bruno, Katelyn A.
Chan, Charles K.
Lee, Andrew S.
Rosenfeld, Stephen S.
Yun, Kyuson
Johnson, Aaron J.
Mitchell, Duane A.
Jiang, Wen
Kim, Betty Y. S.
Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title_full Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title_fullStr Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title_full_unstemmed Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title_short Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
title_sort therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083893/
https://www.ncbi.nlm.nih.gov/pubmed/32198351
http://dx.doi.org/10.1038/s41467-020-15129-8
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