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Volume 25, Issue 2 (March 2023) 25, 171–178; 10.4103/aja202283
Cancer-cell-intrinsic mechanisms shaping the immunosuppressive landscape of prostate cancer
Yini Zhu1,2, Loan Duong1,2, Xuemin Lu1, Xin Lu1,2,3
1 Department of Biological Sciences, Boler-Parseghian Center for Rare and Neglected Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556, USA
2 Integrated Biomedical Sciences Graduate Program, University of Notre Dame, Notre Dame, IN 46556, USA
3 Tumor Microenvironment and Metastasis Program, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN 46202, USA
Correspondence: Dr. Xin Lu (xlu@nd.edu) or Dr. Xuemin Lu (xlu1@nd.edu)
Date of Submission 30-Jun-2022 Date of Acceptance 26-Sep-2022 Date of Web Publication 08-Nov-2022
| Abstract |
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Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types, only a subset of patients shows meaningful clinical responses. In particular, advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy. This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer. Therefore, it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment. Here, we review recent findings that reveal the roles of the genetic alterations, androgen receptor signaling, cancer cell plasticity, and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance. Based on preclinical and clinical observations, a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.
Keywords: immune checkpoint blockade; immunosuppression; immunotherapy; neuroendocrine prostate cancer; prostate cancer
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