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Effective combinatorial immunotherapy for penile squamous cell carcinoma

Author

Listed:
  • Tianhe Huang

    (University of Notre Dame
    Indiana University Melvin and Bren Simon Cancer Center
    The First Affiliated Hospital of Xi’an Jiaotong University)

  • Xi Cheng

    (University of Notre Dame
    Indiana University Melvin and Bren Simon Cancer Center
    , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine)

  • Jad Chahoud

    (The University of Texas MD Anderson Cancer Center)

  • Ahmed Sarhan

    (The University of Texas MD Anderson Cancer Center)

  • Pheroze Tamboli

    (The University of Texas MD Anderson Cancer Center)

  • Priya Rao

    (The University of Texas MD Anderson Cancer Center)

  • Ming Guo

    (The University of Texas MD Anderson Cancer Center)

  • Ganiraju Manyam

    (The University of Texas MD Anderson Cancer Center)

  • Li Zhang

    (University of Cincinnati)

  • Yu Xiang

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Leng Han

    (The University of Texas Health Science Center at Houston McGovern Medical School)

  • Xiaoying Shang

    (The University of Texas MD Anderson Cancer Center)

  • Pingna Deng

    (The University of Texas MD Anderson Cancer Center)

  • Yanting Luo

    (University of Notre Dame)

  • Xuemin Lu

    (University of Notre Dame)

  • Shan Feng

    (School of Life Sciences, Westlake University, Hangzhou)

  • Magaly Martinez Ferrer

    (School of Pharmacy, University of Puerto Rico
    University of Puerto Rico Comprehensive Cancer Center, Medical Sciences Campus)

  • Y. Alan Wang

    (The University of Texas MD Anderson Cancer Center)

  • Ronald A. DePinho

    (The University of Texas MD Anderson Cancer Center)

  • Curtis A. Pettaway

    (The University of Texas MD Anderson Cancer Center)

  • Xin Lu

    (University of Notre Dame
    Indiana University Melvin and Bren Simon Cancer Center)

Abstract

Penile squamous cell carcinoma (PSCC) accounts for over 95% of penile malignancies and causes significant mortality and morbidity in developing countries. Molecular mechanisms and therapies of PSCC are understudied, owing to scarcity of laboratory models. Herein, we describe a genetically engineered mouse model of PSCC, by co-deletion of Smad4 and Apc in the androgen-responsive epithelium of the penis. Mouse PSCC fosters an immunosuppressive microenvironment with myeloid-derived suppressor cells (MDSCs) as a dominant population. Preclinical trials in the model demonstrate synergistic efficacy of immune checkpoint blockade with the MDSC-diminishing drugs cabozantinib or celecoxib. A critical clinical problem of PSCC is chemoresistance to cisplatin, which is induced by Pten deficiency on the backdrop of Smad4/Apc co-deletion. Drug screen studies informed by targeted proteomics identify a few potential therapeutic strategies for PSCC. Our studies have established what we believe to be essential resources for studying PSCC biology and developing therapeutic strategies.

Suggested Citation

  • Tianhe Huang & Xi Cheng & Jad Chahoud & Ahmed Sarhan & Pheroze Tamboli & Priya Rao & Ming Guo & Ganiraju Manyam & Li Zhang & Yu Xiang & Leng Han & Xiaoying Shang & Pingna Deng & Yanting Luo & Xuemin L, 2020. "Effective combinatorial immunotherapy for penile squamous cell carcinoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15980-9
    DOI: 10.1038/s41467-020-15980-9
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