IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-50136-z.html
   My bibliography  Save this article

Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacy

Author

Listed:
  • Hang Zhou

    (Chinese Academy of Sciences)

  • Wenjun Wang

    (Chinese Academy of Sciences)

  • Hairong Xu

    (Chinese Academy of Sciences)

  • Yong Liang

    (University of the Chinese Academy of Sciences)

  • Jiyu Ding

    (Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

  • Mengjie Lv

    (Chinese Academy of Sciences)

  • Boyang Ren

    (Chinese Academy of Sciences)

  • Hua Peng

    (Chinese Academy of Sciences)

  • Yang-Xin Fu

    (Tsinghua University)

  • Mingzhao Zhu

    (Chinese Academy of Sciences
    Chinese Academy of Sciences
    University of the Chinese Academy of Sciences)

Abstract

Type I interferons have been well recognized for their roles in various types of immune cells during tumor immunotherapy. However, their direct effects on tumor cells are less understood. Oxidative phosphorylation is typically latent in tumor cells. Whether oxidative phosphorylation can be targeted for immunotherapy remains unclear. Here, we find that tumor cell responsiveness to type I, but not type II interferons, is essential for CD47-SIRPα blockade immunotherapy in female mice. Mechanistically, type I interferons directly reprogram tumor cell metabolism by activating oxidative phosphorylation for ATP production in an ISG15-dependent manner. ATP extracellular release is also promoted by type I interferons due to enhanced secretory autophagy. Functionally, tumor cells with genetic deficiency in oxidative phosphorylation or autophagy are resistant to CD47-SIRPα blockade. ATP released upon CD47-SIRPα blockade is required for antitumor T cell response induction via P2X7 receptor-mediated dendritic cell activation. Based on this mechanism, combinations with inhibitors of ATP-degrading ectoenzymes, CD39 and CD73, are designed and show synergistic antitumor effects with CD47-SIRPα blockade. Together, these data reveal an important role of type I interferons on tumor cell metabolic reprograming for tumor immunotherapy and provide rational strategies harnessing this mechanism for enhanced efficacy of CD47-SIRPα blockade.

Suggested Citation

  • Hang Zhou & Wenjun Wang & Hairong Xu & Yong Liang & Jiyu Ding & Mengjie Lv & Boyang Ren & Hua Peng & Yang-Xin Fu & Mingzhao Zhu, 2024. "Metabolic reprograming mediated by tumor cell-intrinsic type I IFN signaling is required for CD47-SIRPα blockade efficacy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50136-z
    DOI: 10.1038/s41467-024-50136-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-50136-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-50136-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Di Zhang & Zhanyun Tang & He Huang & Guolin Zhou & Chang Cui & Yejing Weng & Wenchao Liu & Sunjoo Kim & Sangkyu Lee & Mathew Perez-Neut & Jun Ding & Daniel Czyz & Rong Hu & Zhen Ye & Maomao He & Y. Ge, 2019. "Metabolic regulation of gene expression by histone lactylation," Nature, Nature, vol. 574(7779), pages 575-580, October.
    2. Annette Salmeen & Jannik N. Andersen & Michael P. Myers & Tzu-Ching Meng & John A. Hinks & Nicholas K. Tonks & David Barford, 2003. "Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate," Nature, Nature, vol. 423(6941), pages 769-773, June.
    3. Keisuke Yamamoto & Anthony Venida & Julian Yano & Douglas E. Biancur & Miwako Kakiuchi & Suprit Gupta & Albert S. W. Sohn & Subhadip Mukhopadhyay & Elaine Y. Lin & Seth J. Parker & Robert S. Banh & Jo, 2020. "Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I," Nature, Nature, vol. 581(7806), pages 100-105, May.
    4. Robert T. Manguso & Hans W. Pope & Margaret D. Zimmer & Flavian D. Brown & Kathleen B. Yates & Brian C. Miller & Natalie B. Collins & Kevin Bi & Martin W. LaFleur & Vikram R. Juneja & Sarah A. Weiss &, 2017. "In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target," Nature, Nature, vol. 547(7664), pages 413-418, July.
    5. Yingying Zhang & Sheng Sean Su & Shubo Zhao & Zhentao Yang & Chuan-Qi Zhong & Xin Chen & Qixu Cai & Zhang-Hua Yang & Deli Huang & Rui Wu & Jiahuai Han, 2017. "RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    6. Oscar R. Colegio & Ngoc-Quynh Chu & Alison L. Szabo & Thach Chu & Anne Marie Rhebergen & Vikram Jairam & Nika Cyrus & Carolyn E. Brokowski & Stephanie C. Eisenbarth & Gillian M. Phillips & Gary W. Cli, 2014. "Functional polarization of tumour-associated macrophages by tumour-derived lactic acid," Nature, Nature, vol. 513(7519), pages 559-563, September.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sara Orehek & Taja Železnik Ramuta & Duško Lainšček & Špela Malenšek & Martin Šala & Mojca Benčina & Roman Jerala & Iva Hafner-Bratkovič, 2024. "Cytokine-armed pyroptosis induces antitumor immunity against diverse types of tumors," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. Tianshi Feng & Xuemei Zhao & Ping Gu & Wah Yang & Cunchuan Wang & Qingyu Guo & Qiaoyun Long & Qing Liu & Ying Cheng & Jin Li & Cynthia Kwan Yui Cheung & Donghai Wu & Xinyu Kong & Yong Xu & Dewei Ye & , 2022. "Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    3. Le Wang & Dandan Li & Fang Yao & Shanshan Feng & Chao Tong & Rongjia Rao & Meiyan Zhong & Xianqiang Wang & Wei Feng & Zhan Hu & Bo Jin & Li Wang & Shengshou Hu & Bingying Zhou, 2025. "Serpina3k lactylation protects from cardiac ischemia reperfusion injury," Nature Communications, Nature, vol. 16(1), pages 1-21, December.
    4. Nina Frey & Luigi Tortola & David Egli & Sharan Janjuha & Tanja Rothgangl & Kim Fabiano Marquart & Franziska Ampenberger & Manfred Kopf & Gerald Schwank, 2022. "Loss of Rnf31 and Vps4b sensitizes pancreatic cancer to T cell-mediated killing," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Shuangshuang Sun & Zhe Xu & Liying He & Yihui Shen & Yuqing Yan & Xubing Lv & Xujing Zhu & Wei Li & Wei-Ya Tian & Yongjun Zheng & Sen Lin & Yadong Sun & Lei Li, 2024. "Metabolic regulation of cytoskeleton functions by HDAC6-catalyzed α-tubulin lactylation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Marlies Cortés & Agnese Brischetto & M. C. Martinez-Campanario & Chiara Ninfali & Verónica Domínguez & Sara Fernández & Raquel Celis & Anna Esteve-Codina & Juan J. Lozano & Julia Sidorova & Gloria Gar, 2023. "Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    7. Zi-Yi Han & Zhuang-Jiong Fu & Yu-Zhang Wang & Cheng Zhang & Qi-Wen Chen & Jia-Xin An & Xian-Zheng Zhang, 2024. "Probiotics functionalized with a gallium-polyphenol network modulate the intratumor microbiota and promote anti-tumor immune responses in pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Kai Li & Xuan Yu & Yanteng Xu & Haixia Wang & Zheng Liu & Chong Wu & Xing Luo & Jiancheng Xu & Youqiang Fang & Enguo Ju & Shixian Lv & Hon Fai Chan & Yeh-Hsing Lao & Weiling He & Yu Tao & Mingqiang Li, 2025. "Cascaded immunotherapy with implantable dual-drug depots sequentially releasing STING agonists and apoptosis inducers," Nature Communications, Nature, vol. 16(1), pages 1-26, December.
    9. Xiaoyu Liu & Yaping Zhuang & Wei Huang & Zhuozhuo Wu & Yingjie Chen & Qungang Shan & Yuefang Zhang & Zhiyuan Wu & Xiaoyi Ding & Zilong Qiu & Wenguo Cui & Zhongmin Wang, 2023. "Interventional hydrogel microsphere vaccine as an immune amplifier for activated antitumour immunity after ablation therapy," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Lucia Taraborrelli & Yasin Şenbabaoğlu & Lifen Wang & Junghyun Lim & Kerrigan Blake & Noelyn Kljavin & Sarah Gierke & Alexis Scherl & James Ziai & Erin McNamara & Mark Owyong & Shilpa Rao & Aslihan Ka, 2023. "Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Shuang Shang & Chen Yang & Fei Chen & Ren-shen Xiang & Huan Zhang & Shu-yuan Dai & Jing Liu & Xiao-xi Lv & Cheng Zhang & Xiao-tong Liu & Qi Zhang & Shuai-bing Lu & Jia-wei Song & Jiao-jiao Yu & Ji-cha, 2023. "ID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    12. Wanzun Lin & Li Chen & Haojiong Zhang & Xianxin Qiu & Qingting Huang & Fangzhu Wan & Ziyu Le & Shikai Geng & Anlan Zhang & Sufang Qiu & Long Chen & Lin Kong & Jiade J. Lu, 2023. "Tumor-intrinsic YTHDF1 drives immune evasion and resistance to immune checkpoint inhibitors via promoting MHC-I degradation," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    13. Chang Shao & Shuo Tang & Siqin Yu & Chenguang Liu & Yueyang Zhang & Tianyan Wan & Zimeng He & Qi Yuan & Shihan Wu & Hanqing Zhang & Ning Wan & Mengru Zhan & Ren Xiang Tan & Haiping Hao & Hui Ye & Nanx, 2025. "Genetic code expansion reveals site-specific lactylation in living cells reshapes protein functions," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    14. Hanyang Dong & Jianji Zhang & Hui Zhang & Yue Han & Congcong Lu & Chen Chen & Xiaoxia Tan & Siyu Wang & Xue Bai & Guijin Zhai & Shanshan Tian & Tao Zhang & Zhongyi Cheng & Enmin Li & Liyan Xu & Kai Zh, 2022. "YiaC and CobB regulate lysine lactylation in Escherichia coli," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. Stefanie Hiltbrunner & Lena Cords & Sabrina Kasser & Sandra N. Freiberger & Susanne Kreutzer & Nora C. Toussaint & Linda Grob & Isabelle Opitz & Michael Messerli & Martin Zoche & Alex Soltermann & Mar, 2023. "Acquired resistance to anti-PD1 therapy in patients with NSCLC associates with immunosuppressive T cell phenotype," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Z. L. Liu & X. Y. Meng & R. J. Bao & M. Y. Shen & J. J. Sun & W. D. Chen & F. Liu & Y. He, 2024. "Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    17. Lianhui Sun & Yuan Zhang & Boyu Yang & Sijun Sun & Pengshan Zhang & Zai Luo & Tingting Feng & Zelin Cui & Ting Zhu & Yuming Li & Zhengjun Qiu & Guangjian Fan & Chen Huang, 2023. "Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Gaurav Dwivedi & Margaret A Gran & Pritha Bagchi & Melissa L Kemp, 2015. "Dynamic Redox Regulation of IL-4 Signaling," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-20, November.
    19. John P. Finnigan & Jenna H. Newman & Yury Patskovsky & Larysa Patskovska & Andrew S. Ishizuka & Geoffrey M. Lynn & Robert A. Seder & Michelle Krogsgaard & Nina Bhardwaj, 2024. "Structural basis for self-discrimination by neoantigen-specific TCRs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    20. Yusuke Nasu & Abhi Aggarwal & Giang N. T. Le & Camilla Trang Vo & Yuki Kambe & Xinxing Wang & Felix R. M. Beinlich & Ashley Bomin Lee & Tina R. Ram & Fangying Wang & Kelsea A. Gorzo & Yuki Kamijo & Ma, 2023. "Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50136-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.