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Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy

Author

Listed:
  • Elaine Lai-Han Leung

    (Cancer Center, Faculty of Health Sciences; MOE Frontiers Science Center for Precision Oncology, University of Macau)

  • Run-Ze Li

    (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
    Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research)

  • Xing-Xing Fan

    (Macau University of Science and Technology)

  • Lily Yan Wang

    (Janssen Research & Development)

  • Yan Wang

    (Merck Sharp & Dohme)

  • Zebo Jiang

    (Macau University of Science and Technology)

  • Jumin Huang

    (Macau University of Science and Technology)

  • Hu-Dan Pan

    (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
    Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research)

  • Yue Fan

    (Janssen Research & Development)

  • Hongmei Xu

    (Janssen Research & Development)

  • Feng Wang

    (Janssen Research & Development)

  • Haopeng Rui

    (Janssen Research & Development)

  • Piu Wong

    (HiFiBio Therapeutics)

  • Hermi Sumatoh

    (ImmunoScape)

  • Michael Fehlings

    (ImmunoScape)

  • Alessandra Nardin

    (ImmunoScape)

  • Paul Gavine

    (Janssen Research & Development)

  • Longen Zhou

    (Janssen Research & Development)

  • Yabing Cao

    (Kiang Wu Hospital)

  • Liang Liu

    (The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)
    Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research)

Abstract

Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.

Suggested Citation

  • Elaine Lai-Han Leung & Run-Ze Li & Xing-Xing Fan & Lily Yan Wang & Yan Wang & Zebo Jiang & Jumin Huang & Hu-Dan Pan & Yue Fan & Hongmei Xu & Feng Wang & Haopeng Rui & Piu Wong & Hermi Sumatoh & Michae, 2023. "Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40631-0
    DOI: 10.1038/s41467-023-40631-0
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    1. Paul C. Tumeh & Christina L. Harview & Jennifer H. Yearley & I. Peter Shintaku & Emma J. M. Taylor & Lidia Robert & Bartosz Chmielowski & Marko Spasic & Gina Henry & Voicu Ciobanu & Alisha N. West & M, 2014. "PD-1 blockade induces responses by inhibiting adaptive immune resistance," Nature, Nature, vol. 515(7528), pages 568-571, November.
    2. Alexander C. Huang & Michael A. Postow & Robert J. Orlowski & Rosemarie Mick & Bertram Bengsch & Sasikanth Manne & Wei Xu & Shannon Harmon & Josephine R. Giles & Brandon Wenz & Matthew Adamow & Debora, 2017. "T-cell invigoration to tumour burden ratio associated with anti-PD-1 response," Nature, Nature, vol. 545(7652), pages 60-65, May.
    3. 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.
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