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Sooi et al. Cancer Drug Resist 2023;6:656-73 Cancer
DOI: 10.20517/cdr.2023.48
Drug Resistance

Review Open Access

A review of strategies to overcome immune
resistance in the treatment of advanced prostate

cancer

Kenneth Sooi, Robert Walsh, Nesaretnam Kumarakulasinghe, Alvin Wong, Natalie Ngoi
Department of Haematology-Oncology, National University Cancer Institute, Singapore 119228, Singapore.
Correspondence to: Dr. Natalie Ngoi, Department of Haematology-Oncology, National University Cancer Institute, 1E Kent
Ridge Road, NUHS Tower Block Level 7, Singapore 119228, Singapore. E-mail: natalie_yl_ngoi@nuhs.edu.sg

How to cite this article: Sooi K, Walsh R, Kumarakulasinghe N, Wong A, Ngoi N. A review of strategies to overcome immune
resistance in the treatment of advanced prostate cancer. Cancer Drug Resist 2023;6:656-73. https://dx.doi.org/10.20517/cdr.
2023.48

Received: 20 May 2023 First Decision: 14 Jul 2023 Revised: 6 Aug 2023 Accepted: 18 Sep 2023 Published: 25 Sep 2023

Academic Editor: Godefridus J. Peters Copy Editor: Dong-Li Li Production Editor: Dong-Li Li

Abstract
Immunotherapy has become integral in cancer therapeutics over the past two decades and is now part of standard-
of-care treatment in multiple cancer types. While various biomarkers and pathway alterations such as dMMR,
CDK12, and AR-V7 have been identified in advanced prostate cancer to predict immunotherapy responsiveness, the
vast majority of prostate cancer remain intrinsically immune-resistant, as evidenced by low response rates to anti-
PD(L)1 monotherapy. Since regulatory approval of the vaccine therapy sipuleucel-T in the biomarker-unselected
population, there has not been much success with immunotherapy treatment in advanced prostate cancer.
Researchers have looked at various strategies to overcome immune resistance, including the identification of more
biomarkers and the combination of immunotherapy with existing effective prostate cancer treatments. On the
horizon, novel drugs using bispecific T-cell engager (BiTE) and chimeric antigen receptors (CAR) technology are
being explored and have shown promising early efficacy in this disease. Here we discuss the features of the tumour
microenvironment that predispose to immune resistance and rational strategies to enhance antitumour
responsiveness in advanced prostate cancer.

Keywords: Prostate cancer, immunotherapy, immune checkpoint inhibitor, immune resistance, tumour
microenvironment

© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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