Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer

Lisa N Chesner; Fanny Polesso; Julie N Graff; Jessica E Hawley; Alexis K Smith; Arian Lundberg; Rajdeep Das; Tanushree Shenoy; Martin Sjöström; Faming Zhao; Ya-Mei Hu; Simon Linder; William S Chen; Reed M Hawkins; Raunak Shrestha; Xiaolin Zhu; Adam Foye; Haolong Li; Lisa M Kim; Megha Bhalla; Thomas O'loughlin; Duygu Kuzuoglu-Ozturk; Junjie T Hua; Michelle L Badura; Scott Wilkinson; Shana Y Trostel; Andries M Bergman; Davide Ruggero; Charles G Drake; Adam G Sowalsky; Lawrence Fong; Matthew R Cooperberg; Wilbert Zwart; Xiangnan Guan; Alan Ashworth; Zheng Xia; David A Quigley; Luke A Gilbert; Felix Y Feng; Amy E Moran

doi:10.1158/2159-8290.CD-24-0559

Androgen Receptor Inhibition Increases MHC Class I Expression and Improves Immune Response in Prostate Cancer

Cancer Discov. 2025 Mar 3;15(3):481-494. doi: 10.1158/2159-8290.CD-24-0559.

Authors

Lisa N Chesner^{1

2}, Fanny Polesso³, Julie N Graff^{4

5}, Jessica E Hawley^{6

7}, Alexis K Smith^{1

2}, Arian Lundberg^{1

2}, Rajdeep Das^{1

2}, Tanushree Shenoy^{1

8}, Martin Sjöström^{1

2}, Faming Zhao⁹, Ya-Mei Hu⁹, Simon Linder¹⁰, William S Chen^{1

2}, Reed M Hawkins³, Raunak Shrestha^{1

2}, Xiaolin Zhu^{1

8}, Adam Foye^{1

8}, Haolong Li^{1

2}, Lisa M Kim^{1

2}, Megha Bhalla^{1

2}, Thomas O'loughlin^{1

11}, Duygu Kuzuoglu-Ozturk^{1

11}, Junjie T Hua^{1

2}, Michelle L Badura^{1

2}, Scott Wilkinson¹², Shana Y Trostel¹², Andries M Bergman¹⁰, Davide Ruggero^{1

11

13}, Charles G Drake^{14

15}, Adam G Sowalsky¹², Lawrence Fong^{1

6

7

8}, Matthew R Cooperberg^{1

11

16}, Wilbert Zwart¹⁰, Xiangnan Guan⁹, Alan Ashworth^{1

8}, Zheng Xia^{4

9

17}, David A Quigley^{1

11

16}, Luke A Gilbert^{1

11}, Felix Y Feng^#^{1

2

8

11}, Amy E Moran^#^{3

4}

Affiliations

¹ Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California.
² Department of Radiation Oncology, University of California, San Francisco, San Francisco, California.
³ Department of Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, Oregon.
⁴ Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
⁵ VA Portland Health Care System, Portland, Oregon.
⁶ Department of Medicine, University of Washington, Seattle, Washington.
⁷ Clinical Research Division, Fred Hutch Cancer Center, Seattle, Washington.
⁸ Divsion of Hematology and Oncology, Department of Medicine, University of California, San Francisco, San Francisco, California.
⁹ Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon.
¹⁰ Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
¹¹ Department of Urology, University of California San Francisco, San Francisco, California.
¹² Genitourinary Malignancies Branch, National Cancer Institute, Bethesda, Maryland.
¹³ Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, California.
¹⁴ Department of Medicine, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.
¹⁵ Department of Urology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York.
¹⁶ Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
¹⁷ Center for Biomedical Data Science, Oregon Health & Science University, Portland, Oregon.

^# Contributed equally.

Abstract

Immunotherapy options for immune cold tumors, like prostate cancer, are limited. We show that AR downregulates MHCI expression/antigen presentation and that AR inhibition improves T-cell responses and tumor control. This suggests that treatments combining AR inhibitors and checkpoint blockade may improve tumor immune surveillance and antitumor immunity in patients.

MeSH terms

Androgen Receptor Antagonists* / pharmacology
Androgen Receptor Antagonists* / therapeutic use
Animals
Cell Line, Tumor
Histocompatibility Antigens Class I* / genetics
Histocompatibility Antigens Class I* / immunology
Histocompatibility Antigens Class I* / metabolism
Humans
Male
Mice
Prostatic Neoplasms* / drug therapy
Prostatic Neoplasms* / immunology
Prostatic Neoplasms* / metabolism
Receptors, Androgen* / metabolism

Substances

Androgen Receptor Antagonists
Receptors, Androgen
Histocompatibility Antigens Class I

Abstract

MeSH terms

Substances

Grants and funding