Influence of ADT on B7-H3 Expression During CRPC Progression from Hormone-Naïve Prostate Cancer - Beyond the Abstract

In the intricate field of cancer research, the ultimate goal is to find a cure. Prostate cancer (PCa), the second most prevalent cancer globally and a primary cause of cancer-related deaths among North American men, often follows a challenging course. Androgen deprivation therapy (ADT) stands as the standard treatment, reducing or suppressing the hormones that fuel prostate cancer cells.

However, ADT is a paradox. While initially effective, the cancer often retreats into a dormant state. This hibernation can span months or even years before the cancer emerges again in a formidable form known as castration-resistant prostate cancer (CRPC), a condition with limited treatment options and often a fatal outcome. This element of unpredictability amplifies the urgency for more effective therapeutic strategies to treat PCa in its nascent stages and potentially halt the progression to CRPC.

Immunotherapy, a treatment modality that harnesses the body's own immune system to combat cancer, presents one promising approach. Immunotherapies aim to reboot the body's immune surveillance mechanisms, enabling them to identify and eradicate cancer cells.

In various cancer types, the immune system is often 'fooled' into ignoring the cancer cells by a protein called PD-L1. Current immunotherapies target this protein, assisting the immune system in recognizing and annihilating the cancer. However, for a majority of prostate cancer patients, these therapies prove ineffective due to their tumors' low levels of PD-L1.

That's where the focus of our study, the immune checkpoint co-inhibitory ligand B7-H3, comes in. B7-H3 is a protein expressed more abundantly in PCa than in benign prostate tissues. Beyond its role in immune response, this protein is associated with the tumor's aggressiveness, thus making it a valuable target for immunotherapy.

Our study unveiled a noteworthy pattern: B7-H3 protein expression levels ascend during the initial stage of ADT treatment, then gradually decline, hitting their nadir during ADT-induced dormancy, and finally rising again upon cancer relapse. This insight could potentially facilitate patient identification and optimal timing determination for B7-H3 targeting immunotherapies.

Yet, a significant obstacle remains. PCa harbors a 'cold' tumor immune microenvironment (TIME), characterized by limited immune cell infiltration, which hinders immunotherapy efficacy. On the brighter side, ADT is known to induce cancer cell death and stimulate intratumoral inflammation, thereby 'heating up' the tumor, making it more amenable to immune system attack.

Our study proposes the combination of ADT and B7-H3 targeting immunotherapy as a potent strategy to enhance treatment outcomes for PCa, particularly in the early weeks post-ADT before the cancer enters a dormant state. This combinatorial therapy might kill more PCa cells, minimizing the chance of dormancy and potentially reducing the risk of cancer recurrence.

Our findings certainly open a window of promise, yet several questions still remain. What mechanisms, for instance, enable cancer cells to enter dormancy and evade the immune system? Despite these queries, the current research underscores the potential of B7-H3 as a critical player in the fight against prostate cancer, offering a glimmer of hope to patients and their loved ones worldwide.

Written by:

  • Ning Kang, PhD, Department of Experimental Therapeutics, BC Cancer, Vancouver, BC, Canada
  • Yuzhuo Wang, PhD, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada.

  1. Kang N, Xue H, Lin YY, Dong X, Classen A, Wu R, Jin Y, Lin D, Volik S, Ong C, Gleave M, Collins C, Wang YZ. Influence of ADT on B7-H3 expression during CRPC progression from hormone-naïve prostate cancer. Cancer Gene Ther. 2023 Jul 14.
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