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

doi:10.1038/s41467-020-15129-8

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 journal › Article › peer-review

149 Scopus citations

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 language	English (US)
Article number	1508
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-15129-8
State	Published - Mar 20 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), Article 1508. https://doi.org/10.1038/s41467-020-15129-8

von Roemeling, CA, Wang, Y, Qie, Y, Yuan, H, Zhao, H, Liu, X, Yang, Z, Yang, M, Deng, W, Bruno, KA, Chan, CK, Lee, AS, Rosenfeld, SS, Yun, K, Johnson, AJ, Mitchell, DA, Jiang, W & Kim, BYS 2020, 'Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity', Nature Communications, vol. 11, no. 1, 1508. https://doi.org/10.1038/s41467-020-15129-8

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title = "Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity",

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{\textquoteright}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.",

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

note = "Funding Information: This work was supported by grants from the National Institute of Neurological Disorders and Stroke Grant R01 NS104315 (B.Y.S.K.), the Cancer Prevention and Research Institute of Texas RR180017 (W.J.), the American Brain Tumor Association DG1900021 (W.J.), the National Cancer Institute K08 CA241070 (W.J.), and the Preston A. Wells, Jr. Endowment at the University of Florida (D.A.M.). The authors thank Joshua Knight and Laura Lewis-Tuffin and Yuka Gataki for their technical assistance, as well as Christine Wogan from the University of Texas MD Anderson Cancer Center for editorial assistance. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = mar,

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doi = "10.1038/s41467-020-15129-8",

language = "English (US)",

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T1 - Therapeutic modulation of phagocytosis in glioblastoma can activate both innate and adaptive antitumour immunity

AU - von Roemeling, Christina A.

AU - Wang, Yifan

AU - Qie, Yaqing

AU - Yuan, Hengfeng

AU - Zhao, Hai

AU - Liu, Xiujie

AU - Yang, Zhaogang

AU - Yang, Mingming

AU - Deng, Weiye

AU - Bruno, Katelyn A.

AU - Chan, Charles K.

AU - Lee, Andrew S.

AU - Rosenfeld, Stephen S.

AU - Yun, Kyuson

AU - Johnson, Aaron J.

AU - Mitchell, Duane A.

AU - Jiang, Wen

AU - Kim, Betty Y.S.

N1 - Funding Information: This work was supported by grants from the National Institute of Neurological Disorders and Stroke Grant R01 NS104315 (B.Y.S.K.), the Cancer Prevention and Research Institute of Texas RR180017 (W.J.), the American Brain Tumor Association DG1900021 (W.J.), the National Cancer Institute K08 CA241070 (W.J.), and the Preston A. Wells, Jr. Endowment at the University of Florida (D.A.M.). The authors thank Joshua Knight and Laura Lewis-Tuffin and Yuka Gataki for their technical assistance, as well as Christine Wogan from the University of Texas MD Anderson Cancer Center for editorial assistance. Publisher Copyright: © 2020, The Author(s).

PY - 2020/3/20

Y1 - 2020/3/20

N2 - 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.

AB - 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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JO - Nature Communications

JF - Nature Communications

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ER -

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

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