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PIKfyve, expressed by CD11c-positive cells, controls tumor immunity

Author

Listed:
  • Jae Eun Choi

    (University of Michigan
    University of Michigan
    University of California)

  • Yuanyuan Qiao

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Ilona Kryczek

    (University of Michigan
    University of Michigan)

  • Jiali Yu

    (University of Michigan
    University of Michigan)

  • Jonathan Gurkan

    (University of Michigan
    University of Michigan
    Northwestern University)

  • Yi Bao

    (University of Michigan
    University of Michigan)

  • Mahnoor Gondal

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Jean Ching-Yi Tien

    (University of Michigan
    University of Michigan)

  • Tomasz Maj

    (University of Michigan
    University of Michigan)

  • Sahr Yazdani

    (University of Michigan
    University of Michigan
    Children’s Hospital of Philadelphia)

  • Abhijit Parolia

    (University of Michigan
    University of Michigan)

  • Houjun Xia

    (University of Michigan
    University of Michigan)

  • JiaJia Zhou

    (University of Michigan
    University of Michigan)

  • Shuang Wei

    (University of Michigan
    University of Michigan)

  • Sara Grove

    (University of Michigan
    University of Michigan)

  • Linda Vatan

    (University of Michigan
    University of Michigan)

  • Heng Lin

    (University of Michigan
    University of Michigan)

  • Gaopeng Li

    (University of Michigan
    University of Michigan)

  • Yang Zheng

    (University of Michigan
    University of Michigan)

  • Yuping Zhang

    (University of Michigan
    University of Michigan)

  • Xuhong Cao

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Fengyun Su

    (University of Michigan
    University of Michigan)

  • Rui Wang

    (University of Michigan
    University of Michigan)

  • Tongchen He

    (University of Michigan
    University of Michigan)

  • Marcin Cieslik

    (University of Michigan
    University of Michigan
    University of Michigan)

  • Michael D. Green

    (University of Michigan
    University of Michigan
    Department of Radiation Oncology Veterans Affairs Ann Arbor Healthcare System)

  • Weiping Zou

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

  • Arul M. Chinnaiyan

    (University of Michigan
    University of Michigan
    University of Michigan
    University of Michigan)

Abstract

Cancer treatment continues to shift from utilizing traditional therapies to targeted ones, such as protein kinase inhibitors and immunotherapy. Mobilizing dendritic cells (DC) and other myeloid cells with antigen presenting and cancer cell killing capacities is an attractive but not fully exploited approach. Here, we show that PIKFYVE is a shared gene target of clinically relevant protein kinase inhibitors and high expression of this gene in DCs is associated with poor patient response to immune checkpoint blockade (ICB) therapy. Genetic and pharmacological studies demonstrate that PIKfyve ablation enhances the function of CD11c+ cells (predominantly dendritic cells) via selectively altering the non-canonical NF-κB pathway. Both loss of Pikfyve in CD11c+ cells and treatment with apilimod, a potent and specific PIKfyve inhibitor, restrained tumor growth, enhanced DC-dependent T cell immunity, and potentiated ICB efficacy in tumor-bearing mouse models. Furthermore, the combination of a vaccine adjuvant and apilimod reduced tumor progression in vivo. Thus, PIKfyve negatively regulates the function of CD11c+ cells, and PIKfyve inhibition has promise for cancer immunotherapy and vaccine treatment strategies.

Suggested Citation

  • Jae Eun Choi & Yuanyuan Qiao & Ilona Kryczek & Jiali Yu & Jonathan Gurkan & Yi Bao & Mahnoor Gondal & Jean Ching-Yi Tien & Tomasz Maj & Sahr Yazdani & Abhijit Parolia & Houjun Xia & JiaJia Zhou & Shua, 2024. "PIKfyve, expressed by CD11c-positive cells, controls tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48931-9
    DOI: 10.1038/s41467-024-48931-9
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    as
    1. Stephen T. Ferris & Vivek Durai & Renee Wu & Derek J. Theisen & Jeffrey P. Ward & Michael D. Bern & Jesse T. Davidson & Prachi Bagadia & Tiantian Liu & Carlos G. Briseño & Lijin Li & William E. Gillan, 2020. "cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity," Nature, Nature, vol. 584(7822), pages 624-629, August.
    2. Dan R. Robinson & Yi-Mi Wu & Robert J. Lonigro & Pankaj Vats & Erin Cobain & Jessica Everett & Xuhong Cao & Erica Rabban & Chandan Kumar-Sinha & Victoria Raymond & Scott Schuetze & Ajjai Alva & Javed , 2017. "Integrative clinical genomics of metastatic cancer," Nature, Nature, vol. 548(7667), pages 297-303, August.
    3. Weimin Wang & Michael Green & Jae Eun Choi & Miguel Gijón & Paul D. Kennedy & Jeffrey K. Johnson & Peng Liao & Xueting Lang & Ilona Kryczek & Amanda Sell & Houjun Xia & Jiajia Zhou & Gaopeng Li & Jing, 2019. "CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy," Nature, Nature, vol. 569(7755), pages 270-274, May.
    4. Abhijit Parolia & Marcin Cieslik & Shih-Chun Chu & Lanbo Xiao & Takahiro Ouchi & Yuping Zhang & Xiaoju Wang & Pankaj Vats & Xuhong Cao & Sethuramasundaram Pitchiaya & Fengyun Su & Rui Wang & Felix Y. , 2019. "Distinct structural classes of activating FOXA1 alterations in advanced prostate cancer," Nature, Nature, vol. 571(7765), pages 413-418, July.
    5. Daniel Baumann & Tanja Hägele & Julian Mochayedi & Jennifer Drebant & Caroline Vent & Sven Blobner & Julia Han Noll & Irena Nickel & Corinna Schumacher & Sophie Luise Boos & Aline Sophie Daniel & Susa, 2020. "Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy," Nature Communications, Nature, vol. 11(1), pages 1-18, December.
    6. David H. Peng & B. Leticia Rodriguez & Lixia Diao & Pierre-Olivier Gaudreau & Aparna Padhye & Jessica M. Konen & Joshua K. Ochieng & Caleb A. Class & Jared J. Fradette & Laura Gibson & Limo Chen & Jin, 2021. "Th17 cells contribute to combination MEK inhibitor and anti-PD-L1 therapy resistance in KRAS/p53 mutant lung cancers," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    7. Antoni Ribas & Alain Algazi & Paolo A. Ascierto & Marcus O. Butler & Sunandana Chandra & Michael Gordon & Leonel Hernandez-Aya & Donald Lawrence & Jose Lutzky & Wilson H. Miller & Katie M. Campbell & , 2020. "PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
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