IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52079-x.html
   My bibliography  Save this article

Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy

Author

Listed:
  • Avishai Maliah

    (Tel Aviv University)

  • Nadine Santana-Magal

    (Tel Aviv University)

  • Shivang Parikh

    (The Ragon Institute of Mass General)

  • Sagi Gordon

    (Tel Aviv University
    Weizmann Institute of Science)

  • Keren Reshef

    (Tel Aviv University)

  • Yuval Sade

    (Tel Aviv University)

  • Aseel Khateeb

    (Tel Aviv University)

  • Alon Richter

    (Tel Aviv University)

  • Amit Gutwillig

    (Tel Aviv University)

  • Roma Parikh

    (Tel Aviv University)

  • Tamar Golan

    (Tel Aviv University)

  • Matan Krissi

    (Tel Aviv University)

  • Manho Na

    (Tel Aviv University)

  • Gal Binshtok

    (Tel Aviv University)

  • Paulee Manich

    (Tel Aviv University)

  • Nadav Elkoshi

    (Tel Aviv University)

  • Sharon Grisaru-Tal

    (Tel Aviv University)

  • Valentina Zemser-Werner

    (Tel Aviv Sourasky Medical Center)

  • Ronen Brenner

    (Institute of Oncology)

  • Hananya Vaknine

    (Institute of Pathology)

  • Eran Nizri

    (Tel Aviv University)

  • Lilach Moyal

    (Tel-Aviv University and the Division of Dermatology, Rabin Medical Center)

  • Iris Amitay-Laish

    (Tel-Aviv University and the Division of Dermatology, Rabin Medical Center)

  • Luiza Rosemberg

    (Tel Aviv University)

  • Ariel Munitz

    (Tel Aviv University)

  • Noga Kronfeld-Schor

    (Tel Aviv University)

  • Eric Shifrut

    (Tel Aviv University
    Tel Aviv University
    Tel Aviv Sourasky Medical Center)

  • Oren Kobiler

    (Tel Aviv University)

  • Asaf Madi

    (Tel Aviv University)

  • Tamar Geiger

    (Weizmann Institute of Science)

  • Yaron Carmi

    (Tel Aviv University)

  • Carmit Levy

    (Tel Aviv University)

Abstract

T cell inhibitory mechanisms prevent autoimmune reactions, while cancer immunotherapy aims to remove these inhibitory signals. Chronic ultraviolet (UV) exposure attenuates autoimmunity through promotion of poorly understood immune-suppressive mechanisms. Here we show that mice with subcutaneous melanoma are not responsive to anti-PD1 immunotherapy following chronic UV irradiation, given prior to tumor injection, due to the suppression of T cell killing ability in skin-draining lymph nodes. Using mass cytometry and single-cell RNA-sequencing analyzes, we discover that skin-specific, UV-induced suppression of T-cells killing activity is mediated by upregulation of a Ly6ahigh T-cell subpopulation. Independently of the UV effect, Ly6ahigh T cells are induced by chronic type-1 interferon in the tumor microenvironment. Treatment with an anti-Ly6a antibody enhances the anti-tumoral cytotoxic activity of T cells and reprograms their mitochondrial metabolism via the Erk/cMyc axis. Treatment with an anti-Ly6a antibody inhibits tumor growth in mice resistant to anti-PD1 therapy. Applying our findings in humans could lead to an immunotherapy treatment for patients with resistance to existing treatments.

Suggested Citation

  • Avishai Maliah & Nadine Santana-Magal & Shivang Parikh & Sagi Gordon & Keren Reshef & Yuval Sade & Aseel Khateeb & Alon Richter & Amit Gutwillig & Roma Parikh & Tamar Golan & Matan Krissi & Manho Na &, 2024. "Crosslinking of Ly6a metabolically reprograms CD8 T cells for cancer immunotherapy," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52079-x
    DOI: 10.1038/s41467-024-52079-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52079-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52079-x?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. Lea Monteran & Nour Ershaid & Hila Doron & Yael Zait & Ye’ela Scharff & Shahar Ben-Yosef & Camila Avivi & Iris Barshack & Amir Sonnenblick & Neta Erez, 2022. "Chemotherapy-induced complement signaling modulates immunosuppression and metastatic relapse in breast cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Ang Cui & Teddy Huang & Shuqiang Li & Aileen Ma & Jorge L. Pérez & Chris Sander & Derin B. Keskin & Catherine J. Wu & Ernest Fraenkel & Nir Hacohen, 2024. "Dictionary of immune responses to cytokines at single-cell resolution," Nature, Nature, vol. 625(7994), pages 377-384, January.
    3. Caroline Robert, 2020. "A decade of immune-checkpoint inhibitors in cancer therapy," Nature Communications, Nature, vol. 11(1), pages 1-3, 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. Qianqian Ming & Daniel Antfolk & David A. Price & Anna Manturova & Elliot Medina & Srishti Singh & Charlotte Mason & Timothy H. Tran & Keiran S. M. Smalley & Daisy W. Leung & Vincent C. Luca, 2024. "Structural basis for mouse LAG3 interactions with the MHC class II molecule I-Ab," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Yue Wang & Shi-Kun Zhou & Yan Wang & Zi-Dong Lu & Yue Zhang & Cong-Fei Xu & Jun Wang, 2023. "Engineering tumor-specific gene nanomedicine to recruit and activate T cells for enhanced immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    3. Nandini Pal Basak & Kowshik Jaganathan & Biswajit Das & Oliyarasi Muthusamy & Rajashekar M & Ritu Malhotra & Amit Samal & Moumita Nath & Ganesh MS & Amritha Prabha Shankar & Prakash BV & Vijay Pillai , 2024. "Tumor histoculture captures the dynamic interactions between tumor and immune components in response to anti-PD1 in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Caihua Zhang & Kang Li & Hongzhang Zhu & Maosheng Cheng & Shuang Chen & Rongsong Ling & Cheng Wang & Demeng Chen, 2024. "ITGB6 modulates resistance to anti-CD276 therapy in head and neck cancer by promoting PF4+ macrophage infiltration," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    5. Pooja Middha & Rohit Thummalapalli & Michael J. Betti & Lydia Yao & Zoe Quandt & Karmugi Balaratnam & Cosmin A. Bejan & Eduardo Cardenas & Christina J. Falcon & David M. Faleck & Matthew A. Gubens & S, 2024. "Polygenic risk score for ulcerative colitis predicts immune checkpoint inhibitor-mediated colitis," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    6. Jianting Long & Xihe Chen & Mian He & Shudan Ou & Yunhe Zhao & Qingjia Yan & Minjun Ma & Jingyu Chen & Xuping Qin & Xiangjun Zhou & Junjun Chu & Yanyan Han, 2024. "HLA-class II restricted TCR targeting human papillomavirus type 18 E7 induces solid tumor remission in mice," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Monika Licaj & Rana Mhaidly & Yann Kieffer & Hugo Croizer & Claire Bonneau & Arnaud Meng & Lounes Djerroudi & Kevin Mujangi-Ebeka & Hocine R. Hocine & Brigitte Bourachot & Ilaria Magagna & Renaud Lecl, 2024. "Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway," Nature Communications, Nature, vol. 15(1), pages 1-27, 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_s41467-024-52079-x. 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.