IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32567-8.html
   My bibliography  Save this article

Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice

Author

Listed:
  • Rachael M. Zemek

    (National Centre for Asbestos Related Diseases
    University of Western Australia
    University of Western Australia)

  • Wee Loong Chin

    (University of Western Australia
    Sir Charles Gairdner Hospital
    University of Western Australia)

  • Vanessa S. Fear

    (National Centre for Asbestos Related Diseases
    University of Western Australia
    University of Western Australia)

  • Ben Wylie

    (University of Western Australia)

  • Thomas H. Casey

    (National Centre for Asbestos Related Diseases
    University of Western Australia)

  • Cath Forbes

    (National Centre for Asbestos Related Diseases
    University of Western Australia
    University of Western Australia)

  • Caitlin M. Tilsed

    (National Centre for Asbestos Related Diseases
    University of Western Australia)

  • Louis Boon

    (Polpharma Biologics, Yalelaan 46, Alexander Numan Building)

  • Belinda B. Guo

    (The University of Western Australia, Nedlands)

  • Anthony Bosco

    (University of Western Australia)

  • Alistair R. R. Forrest

    (The University of Western Australia, Nedlands)

  • Michael J. Millward

    (Sir Charles Gairdner Hospital
    University of Western Australia)

  • Anna K. Nowak

    (National Centre for Asbestos Related Diseases
    Sir Charles Gairdner Hospital
    University of Western Australia)

  • Richard A. Lake

    (National Centre for Asbestos Related Diseases
    University of Western Australia)

  • Timo Lassmann

    (University of Western Australia)

  • W. Joost Lesterhuis

    (National Centre for Asbestos Related Diseases
    University of Western Australia
    University of Western Australia)

Abstract

The biological determinants of the response to immune checkpoint blockade (ICB) in cancer remain incompletely understood. Little is known about dynamic biological events that underpin therapeutic efficacy due to the inability to frequently sample tumours in patients. Here, we map the transcriptional profiles of 144 responding and non-responding tumours within two mouse models at four time points during ICB. We find that responding tumours display on/fast-off kinetics of type-I-interferon (IFN) signaling. Phenocopying of this kinetics using time-dependent sequential dosing of recombinant IFNs and neutralizing antibodies markedly improves ICB efficacy, but only when IFNβ is targeted, not IFNα. We identify Ly6C+/CD11b+ inflammatory monocytes as the primary source of IFNβ and find that active type-I-IFN signaling in tumour-infiltrating inflammatory monocytes is associated with T cell expansion in patients treated with ICB. Together, our results suggest that on/fast-off modulation of IFNβ signaling is critical to the therapeutic response to ICB, which can be exploited to drive clinical outcomes towards response.

Suggested Citation

  • Rachael M. Zemek & Wee Loong Chin & Vanessa S. Fear & Ben Wylie & Thomas H. Casey & Cath Forbes & Caitlin M. Tilsed & Louis Boon & Belinda B. Guo & Anthony Bosco & Alistair R. R. Forrest & Michael J. , 2022. "Temporally restricted activation of IFNβ signaling underlies response to immune checkpoint therapy in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32567-8
    DOI: 10.1038/s41467-022-32567-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32567-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32567-8?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. Gioele La Manno & Ruslan Soldatov & Amit Zeisel & Emelie Braun & Hannah Hochgerner & Viktor Petukhov & Katja Lidschreiber & Maria E. Kastriti & Peter Lönnerberg & Alessandro Furlan & Jean Fan & Lars E, 2018. "RNA velocity of single cells," Nature, Nature, vol. 560(7719), pages 494-498, August.
    2. Vân Anh Huynh-Thu & Alexandre Irrthum & Louis Wehenkel & Pierre Geurts, 2010. "Inferring Regulatory Networks from Expression Data Using Tree-Based Methods," PLOS ONE, Public Library of Science, vol. 5(9), pages 1-10, September.
    3. Sanjeev Mariathasan & Shannon J. Turley & Dorothee Nickles & Alessandra Castiglioni & Kobe Yuen & Yulei Wang & Edward E. Kadel III & Hartmut Koeppen & Jillian L. Astarita & Rafael Cubas & Suchit Jhunj, 2018. "TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells," Nature, Nature, vol. 554(7693), pages 544-548, February.
    4. M. Büttner & J. Ostner & C. L. Müller & F. J. Theis & B. Schubert, 2021. "scCODA is a Bayesian model for compositional single-cell data analysis," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    5. Roy S. Herbst & Jean-Charles Soria & Marcin Kowanetz & Gregg D. Fine & Omid Hamid & Michael S. Gordon & Jeffery A. Sosman & David F. McDermott & John D. Powderly & Scott N. Gettinger & Holbrook E. K. , 2014. "Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients," Nature, Nature, vol. 515(7528), pages 563-567, November.
    6. Eddie Cano-Gamez & Blagoje Soskic & Theodoros I. Roumeliotis & Ernest So & Deborah J. Smyth & Marta Baldrighi & David Willé & Nikolina Nakic & Jorge Esparza-Gordillo & Christopher G. C. Larminie & Pao, 2020. "Single-cell transcriptomics identifies an effectorness gradient shaping the response of CD4+ T cells to cytokines," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    7. Chan-Young Ock & Jun-Eul Hwang & Bhumsuk Keam & Sang-Bae Kim & Jae-Jun Shim & Hee-Jin Jang & Sarang Park & Bo Hwa Sohn & Minse Cha & Jaffer A. Ajani & Scott Kopetz & Keun-Wook Lee & Tae Min Kim & Dae , 2017. "Genomic landscape associated with potential response to anti-CTLA-4 treatment in cancers," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    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. Jing Liu & Xia Bu & Chen Chu & Xiaoming Dai & John M. Asara & Piotr Sicinski & Gordon J. Freeman & Wenyi Wei, 2023. "PRMT1 mediated methylation of cGAS suppresses anti-tumor immunity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Jingjing Qi & Hongxiang Sun & Yao Zhang & Zhengting Wang & Zhenzhen Xun & Ziyi Li & Xinyu Ding & Rujuan Bao & Liwen Hong & Wenqing Jia & Fei Fang & Hongzhi Liu & Lei Chen & Jie Zhong & Duowu Zou & Lia, 2022. "Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    3. Yichi Niu & Jiayi Luo & Chenghang Zong, 2024. "Single-cell total-RNA profiling unveils regulatory hubs of transcription factors," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Drew R. Neavin & Angela M. Steinmann & Nona Farbehi & Han Sheng Chiu & Maciej S. Daniszewski & Himanshi Arora & Yasmin Bermudez & Cátia Moutinho & Chia-Ling Chan & Monique Bax & Mubarika Tyebally & Vi, 2023. "A village in a dish model system for population-scale hiPSC studies," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    5. Xinyu Bai & Grace H. Attrill & Tuba N. Gide & Peter M. Ferguson & Kazi J. Nahar & Ping Shang & Ismael A. Vergara & Umaimainthan Palendira & Ines Pires Silva & Matteo S. Carlino & Alexander M. Menzies , 2024. "Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Hong Yuen Wong & Quanhu Sheng & Amanda B. Hesterberg & Sarah Croessmann & Brenda L. Rios & Khem Giri & Jorgen Jackson & Adam X. Miranda & Evan Watkins & Kerry R. Schaffer & Meredith Donahue & Elizabet, 2022. "Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    7. Huanhuan Tan & Weixu Wang & Congjin Zhou & Yanfeng Wang & Shu Zhang & Pinglan Yang & Rui Guo & Wei Chen & Jinwen Zhang & Lan Ye & Yiqiang Cui & Ting Ni & Ke Zheng, 2023. "Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Mike B. Barnkob & Yale S. Michaels & Violaine André & Philip S. Macklin & Uzi Gileadi & Salvatore Valvo & Margarida Rei & Corinna Kulicke & Ji-Li Chen & Vitul Jain & Victoria K. Woodcock & Huw Colin-Y, 2024. "Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    9. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    10. Christoph Ziegenhain & Rickard Sandberg, 2021. "BAMboozle removes genetic variation from human sequence data for open data sharing," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    11. Yoshiaki Yasumizu & Naganari Ohkura & Hisashi Murata & Makoto Kinoshita & Soichiro Funaki & Satoshi Nojima & Kansuke Kido & Masaharu Kohara & Daisuke Motooka & Daisuke Okuzaki & Shuji Suganami & Eriko, 2022. "Myasthenia gravis-specific aberrant neuromuscular gene expression by medullary thymic epithelial cells in thymoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Jialiang S. Wang & Tushar Kamath & Courtney M. Mazur & Fatemeh Mirzamohammadi & Daniel Rotter & Hironori Hojo & Christian D. Castro & Nicha Tokavanich & Rushi Patel & Nicolas Govea & Tetsuya Enishi & , 2021. "Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    13. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    14. Feng Xie & Xiaoxue Zhou & Peng Su & Heyu Li & Yifei Tu & Jinjin Du & Chen Pan & Xiang Wei & Min Zheng & Ke Jin & Liyan Miao & Chao Wang & Xuli Meng & Hans Dam & Peter Dijke & Long Zhang & Fangfang Zho, 2022. "Breast cancer cell-derived extracellular vesicles promote CD8+ T cell exhaustion via TGF-β type II receptor signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    15. David J. Dittmar & Franziska Pielmeier & Nicholas Strieder & Alexander Fischer & Michael Herbst & Hanna Stanewsky & Niklas Wenzl & Eveline Röseler & Rüdiger Eder & Claudia Gebhard & Lucia Schwarzfisch, 2024. "Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Jonas Engesser & Robin Khatri & Darius P. Schaub & Yu Zhao & Hans-Joachim Paust & Zeba Sultana & Nariaki Asada & Jan-Hendrik Riedel & Varshi Sivayoganathan & Anett Peters & Anna Kaffke & Saskia-Lariss, 2024. "Immune profiling-based targeting of pathogenic T cells with ustekinumab in ANCA-associated glomerulonephritis," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    17. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    18. Guo Li & Saranya Srinivasan & Liwen Wang & Chaoyu Ma & Kai Guo & Wenhao Xiao & Wei Liao & Shruti Mishra & Xin Zhang & Yuanzheng Qiu & Qianjin Lu & Yong Liu & Nu Zhang, 2022. "TGF-β-dependent lymphoid tissue residency of stem-like T cells limits response to tumor vaccine," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    19. Seong Eun Lee & Seongyeol Park & Shinae Yi & Na Rae Choi & Mi Ae Lim & Jae Won Chang & Ho-Ryun Won & Je Ryong Kim & Hye Mi Ko & Eun-Jae Chung & Young Joo Park & Sun Wook Cho & Hyeong Won Yu & June You, 2024. "Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. David G. Priest & Takeshi Ebihara & Janyerkye Tulyeu & Jonas N. Søndergaard & Shuhei Sakakibara & Fuminori Sugihara & Shunichiro Nakao & Yuki Togami & Jumpei Yoshimura & Hiroshi Ito & Shinya Onishi & , 2024. "Atypical and non-classical CD45RBlo memory B cells are the majority of circulating SARS-CoV-2 specific B cells following mRNA vaccination or COVID-19," Nature Communications, Nature, vol. 15(1), pages 1-21, 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:13:y:2022:i:1:d:10.1038_s41467-022-32567-8. 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.