IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-37379-y.html
   My bibliography  Save this article

Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis

Author

Listed:
  • Hong Sheng Quah

    (National Cancer Centre
    Duke-NUS Medical School)

  • Elaine Yiqun Cao

    (Duke-NUS Medical School)

  • Lisda Suteja

    (National Cancer Centre
    Duke-NUS Medical School)

  • Constance H. Li

    (National Cancer Centre
    Duke-NUS Medical School)

  • Hui Sun Leong

    (National Cancer Centre)

  • Fui Teen Chong

    (National Cancer Centre)

  • Shilpi Gupta

    (Agency for Science Technology and Research (A*STAR))

  • Camille Arcinas

    (National Cancer Centre
    Duke-NUS Medical School)

  • John F. Ouyang

    (Duke-NUS Medical School)

  • Vivian Ang

    (Agency for Science Technology and Research (A*STAR))

  • Teja Celhar

    (Agency for Science, Technology and Research (A*STAR))

  • Yunqian Zhao

    (Agency for Science, Technology and Research (A*STAR))

  • Hui Chen Tay

    (Agency for Science, Technology and Research (A*STAR))

  • Jerry Chan

    (KK Women’s and Children’s Hospital)

  • Takeshi Takahashi

    (Central Institute for Experimental Animals (CIEA))

  • Daniel S. W. Tan

    (National Cancer Centre
    Duke-NUS Medical School
    National Cancer Centre)

  • Subhra K. Biswas

    (Agency for Science Technology and Research (A*STAR))

  • Owen J. L. Rackham

    (Duke-NUS Medical School
    University of Southampton
    The British Library)

  • N. Gopalakrishna Iyer

    (National Cancer Centre
    Duke-NUS Medical School
    National Cancer Centre
    National Cancer Centre)

Abstract

Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a subpopulation of pre-metastatic cells, driven by actionable pathways including AXL and AURK. Blocking these two proteins blunts tumor invasion in patient-derived cultures. Furthermore, scRNAseq analyses of tumor-infiltrating CD8 + T-lymphocytes show two distinct trajectories to T-cell dysfunction, corroborated by their clonal architecture based on single-cell T-cell receptor sequencing. By determining key modulators of these trajectories, followed by validation using external datasets and functional experiments, we uncover a role for SOX4 in mediating T-cell exhaustion. Finally, interactome analyses between pre-metastatic tumor cells and CD8 + T-lymphocytes uncover a putative role for the Midkine pathway in immune-modulation and this is confirmed by scRNAseq of tumors from humanized mice. Aside from specific findings, this study demonstrates the importance of tumor heterogeneity analyses in identifying key vulnerabilities during early metastasis.

Suggested Citation

  • Hong Sheng Quah & Elaine Yiqun Cao & Lisda Suteja & Constance H. Li & Hui Sun Leong & Fui Teen Chong & Shilpi Gupta & Camille Arcinas & John F. Ouyang & Vivian Ang & Teja Celhar & Yunqian Zhao & Hui C, 2023. "Single cell analysis in head and neck cancer reveals potential immune evasion mechanisms during early metastasis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37379-y
    DOI: 10.1038/s41467-023-37379-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-37379-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-37379-y?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. Ankur Sharma & Elaine Yiqun Cao & Vibhor Kumar & Xiaoqian Zhang & Hui Sun Leong & Angeline Mei Lin Wong & Neeraja Ramakrishnan & Muhammad Hakimullah & Hui Min Vivian Teo & Fui Teen Chong & Shumei Chia, 2018. "Longitudinal single-cell RNA sequencing of patient-derived primary cells reveals drug-induced infidelity in stem cell hierarchy," Nature Communications, Nature, vol. 9(1), pages 1-17, December.
    2. Thorsten R. Mempel & Sarah E. Henrickson & Ulrich H. von Andrian, 2004. "T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases," Nature, Nature, vol. 427(6970), pages 154-159, January.
    3. Yannick Simoni & Etienne Becht & Michael Fehlings & Chiew Yee Loh & Si-Lin Koo & Karen Wei Weng Teng & Joe Poh Sheng Yeong & Rahul Nahar & Tong Zhang & Hassen Kared & Kaibo Duan & Nicholas Ang & Micha, 2018. "Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates," Nature, Nature, vol. 557(7706), pages 575-579, May.
    4. 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.
    5. Juliane Winkler & Abisola Abisoye-Ogunniyan & Kevin J. Metcalf & Zena Werb, 2020. "Concepts of extracellular matrix remodelling in tumour progression and metastasis," Nature Communications, Nature, vol. 11(1), pages 1-19, December.
    6. Shumei Chia & Joo-Leng Low & Xiaoqian Zhang & Xue-Lin Kwang & Fui-Teen Chong & Ankur Sharma & Denis Bertrand & Shen Yon Toh & Hui-Sun Leong & Matan T. Thangavelu & Jacqueline S. G. Hwang & Kok-Hing Li, 2017. "Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Soumitra Ghosh & Jovan Isma & Paola Ostano & Luigi Mazzeo & Annagiada Toniolo & Monalisa Das & Joni R. White & Christian Simon & G. Paolo Dotto, 2024. "Nuclear lamin A/C phosphorylation by loss of androgen receptor leads to cancer-associated fibroblast activation," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    2. 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.

    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. Daniele Ramazzotti & Fabrizio Angaroni & Davide Maspero & Gianluca Ascolani & Isabella Castiglioni & Rocco Piazza & Marco Antoniotti & Alex Graudenzi, 2022. "Variant calling from scRNA-seq data allows the assessment of cellular identity in patient-derived cell lines," Nature Communications, Nature, vol. 13(1), pages 1-3, December.
    2. Xiuling Shen & Haoyi Zhou & Xin Zhou & Zongchao Liu & Xiangxi Meng & Linyu Zhang & Yufei Song & Rui Guo & Fei Wang & Kui Li & Wenqing Li & Zhi Yang & Zhaofei Liu & Nan Li, 2024. "68Ga-grazytracer PET for noninvasive assessment of response to immunotherapy in solid tumors and lymphomas: a phase 1/2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    3. 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.
    4. 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.
    5. Irma Telarovic & Carmen S. M. Yong & Lisa Kurz & Irene Vetrugno & Sabrina Reichl & Alba Sanchez Fernandez & Hung-Wei Cheng & Rona Winkler & Matthias Guckenberger & Anja Kipar & Burkhard Ludewig & Mart, 2024. "Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Junyi Chen & Xiaoying Wang & Anjun Ma & Qi-En Wang & Bingqiang Liu & Lang Li & Dong Xu & Qin Ma, 2022. "Deep transfer learning of cancer drug responses by integrating bulk and single-cell RNA-seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. 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.
    8. 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.
    9. Brian J Schmidt & Jason A Papin & Michael B Lawrence, 2009. "Nano-motion Dynamics are Determined by Surface-Tethered Selectin Mechanokinetics and Bond Formation," PLOS Computational Biology, Public Library of Science, vol. 5(12), pages 1-19, December.
    10. 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.
    11. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    12. Mengxue Zhou & Jiaxin Wang & Jiaxing Pan & Hui Wang & Lujia Huang & Bo Hou & Yi Lai & Fengyang Wang & Qingxiang Guan & Feng Wang & Zhiai Xu & Haijun Yu, 2023. "Nanovesicles loaded with a TGF-β receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Kenneth Letendre & Emmanuel Donnadieu & Melanie E Moses & Judy L Cannon, 2015. "Bringing Statistics Up to Speed with Data in Analysis of Lymphocyte Motility," PLOS ONE, Public Library of Science, vol. 10(5), pages 1-18, May.
    14. Han Luo & Xuyang Xia & Li-Bin Huang & Hyunsu An & Minyuan Cao & Gyeong Dae Kim & Hai-Ning Chen & Wei-Han Zhang & Yang Shu & Xiangyu Kong & Zhixiang Ren & Pei-Heng Li & Yang Liu & Huairong Tang & Rongh, 2022. "Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Wei Cheng & Hao-Long Li & Shao-Yan Xi & Xiao-Feng Zhang & Yun Zhu & Le Xing & Yan-Xuan Mo & Mei-Mei Li & Fan-En Kong & Wen-Jie Zhu & Xiao-Gang Chen & Hui-Qing Cui & Zhi-Ming Cao & Yuan-Feng Gong & Yun, 2021. "Growth differentiation factor 1-induced tumour plasticity provides a therapeutic window for immunotherapy in hepatocellular carcinoma," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    16. Fan Xia & Cheng-Rui Qian & Zhou Xun & Yannick Hamon & Anne-Marie Sartre & Anthony Formisano & Sébastien Mailfert & Marie-Claire Phelipot & Cyrille Billaudeau & Sébastien Jaeger & Jacques Nunès & Xiao-, 2018. "TCR and CD28 Concomitant Stimulation Elicits a Distinctive Calcium Response in Naive T Cells," Post-Print hal-02084941, HAL.
    17. Judit Svensson-Arvelund & Sara Cuadrado-Castano & Gvantsa Pantsulaia & Kristy Kim & Mark Aleynick & Linda Hammerich & Ranjan Upadhyay & Michael Yellin & Henry Marsh & Daniel Oreper & Suchit Jhunjhunwa, 2022. "Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    18. 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.
    19. Jani Huuhtanen & Liang Chen & Emmi Jokinen & Henna Kasanen & Tapio Lönnberg & Anna Kreutzman & Katriina Peltola & Micaela Hernberg & Chunlin Wang & Cassian Yee & Harri Lähdesmäki & Mark M. Davis & Sat, 2022. "Evolution and modulation of antigen-specific T cell responses in melanoma patients," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Jonathan J. Swietlik & Stefanie Bärthel & Chiara Falcomatà & Diana Fink & Ankit Sinha & Jingyuan Cheng & Stefan Ebner & Peter Landgraf & Daniela C. Dieterich & Henrik Daub & Dieter Saur & Felix Meissn, 2023. "Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation," 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:14:y:2023:i:1:d:10.1038_s41467-023-37379-y. 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.