Combining intratumoral Treg depletion with androgen deprivation therapy (ADT): preclinical activity in the Myc-CaP model

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Immune checkpoint blockade has shown promising antitumor activity against a variety of tumor types. However, responses in castration-resistant prostate cancer remain relatively rare—potentially due to low baseline levels of infiltration. Using an immunocompetent cMyc-driven model (Myc-CaP), we sought to understand the immune infiltrate induced by androgen deprivation therapy (ADT) and to leverage that infiltration toward therapeutic benefit.


Using flow cytometry, qPCR and IHC, we quantified ADT-induced immune infiltration in terms of cell type and function. Preclinical treatment studies tested the combinatorial effects of ADT and immune checkpoint blockade using tumor outgrowth and overall survival as end points.


ADT induces a complex pro-inflammatory infiltrate. This pro-inflammatory infiltrate was apparent in the early postcastration period but diminished as castration resistance emerged. Combining ADT with tumor-infiltrating regulatory T cell (Treg) depletion using a depleting anti-CTLA-4 antibody significantly delayed the development of castration resistance and prolonged survival of a fraction of tumor-bearing mice. Immunotherapy as a monotherapy failed to provide a survival benefit and was ineffective if not administered in the peri-castration period.


The immune infiltrate induced by ADT is diverse and varies over time. Therapeutic strategies focusing on depleting Tregs in the peri-castration period are of particular interest.

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The authors thank Ms. Muniza Uddin and Dr. Alan Meeker for assistance with immunohistochemistry.

Financial support

A.G. was supported by NIH T32GM007309. C.G.D. was supported by NIH R01CA127153, the Patrick C. Walsh Prostate Cancer Research Fund, the One-in-Six Foundation, the Prostate Cancer Foundation, and the Melanoma Research Alliance

Author information

Author notes

    • Christina M. Kochel

    Present address: Tizona Therapeutics, South San Francisco, CA, USA

    • Brian J. Francica

    Present address: Aduro Biotech, Berkeley, CA, USA

    • Charles G. Drake

    Present address: Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA


  1. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Ying-Chun Shen
    • , Ali Ghasemzadeh
    • , Christina M. Kochel
    • , Brian J. Francica
    • , Zoila A. Lopez-Bujanda
    • , Maria A. Carrera Haro
    • , Ada Tam
    •  & Charles G. Drake
  2. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

    • Ying-Chun Shen
    •  & Thomas R. Nirschl
  3. Graduate Institute of Oncology, School of Medicine, National Taiwan University, Taipei, Taiwan

    • Ying-Chun Shen
  4. Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Ali Ghasemzadeh
    • , Thomas R. Nirschl
    • , Zoila A. Lopez-Bujanda
    • , Maria A. Carrera Haro
    •  & Ada Tam
  5. Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Ali Ghasemzadeh
  6. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA

    • Ali Ghasemzadeh
    • , Zoila A. Lopez-Bujanda
    • , Maria A. Carrera Haro
    •  & Charles G. Drake
  7. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    • Zoila A. Lopez-Bujanda
    •  & Robert A. Anders
  8. Bristol-Myers Squibb, Redwood City, CA, USA

    • Mark J. Selby
    •  & Alan J. Korman
  9. The Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA

    • Charles G. Drake


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Conflicts of interest

C.G.D. has served as a paid consultant to Agenus, Bristol Myers Squibb, Compugen, Dendreon, Merck, and Roche Genentech and has received sponsored research funding (institutional) from Bristol Myers Squibb under the International Immuno-Oncology Network (IIoN). A.K. and M.J.S. are paid employees of Bristol Myers Squibb. The other authors declare that they have no competing interests.

Corresponding author

Correspondence to Charles G. Drake.

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