Signaling new therapeutic opportunities: cytokines in prostate cancer

ABSTRACT

Introduction

Despite FDA approval of sipuleucel-T in 2010, endeavors to use immune checkpoint inhibitors in unselected prostate cancer patients have not improved clinical outcomes. These efforts include studies with anti-PD1/PD-L1 and anti-CTLA-4 alone and in combination with existing standards of care. These strategies are generally T-cell centric and disregard the broader complex and pleiotropic components of the prostate cancer tumor microenvironment such as natural killer cells, myeloid-derived suppressor cells, and tumor-associated macrophages.

Areas covered

We performed an online literature search and undertook a review of existing preclinical and clinical literature for cytokine-based therapy related to prostate cancer, specifically on interleukin (IL)-2, IL-15, IL-12, IL-23, IL-8, and transforming growth factor (TGF)-β.

Expert opinion

Cytokine-based therapies present an alternative immune strategy to target the pleiotropic prostate cancer tumor microenvironment beyond T-cells. Future immunotherapy strategies in prostate cancer should address these immune cell populations, which may play more important roles in the prostate cancer tumor microenvironment.

KEYWORDS:

• Cytokines
• prostate cancer
• immunotherapy
• immunocytokines
• tumor microenvironment
• cell therapy

Article highlights

• Immunotherapy has been slow to progress in prostate cancer, with checkpoint inhibitors failing to improve survival in unselected patients thus far.

• T-cells may not be the primary drivers in the prostate cancer TME. Instead, other cells in the tumor microenvironment (TME) such as natural killer (NK) cells, tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) may play more dominant roles,

• Cytokine strategies impact these cells in addition to T-cells and may be the key to unlocking immunotherapy in prostate cancer.

• This article summarizes preclinical and clinical literature on interleukin (IL)-2, IL-15, IL-12, IL-23, IL-8, and transforming growth factor (TGF)-β pertaining to prostate cancer.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

A reviewer on this manuscript has disclosed the following: Advisory Board: Bristol-Myers Squibb, Genentech, EMD Serono, Merck, Sanofi, Seattle Genetics/Astellas, AstraZeneca, Exelixis, Janssen, Bicycle Therapeutics, Pfizer, Gilead, Scholar Rock, G1 Therapeutics, Eli Lilly/Loxo Oncology, Infinity Pharmaceuticals, Lucence Health, IMV; Research Support: Sanofi (iaward), AstraZeneca, Gilead, Helsinn, Lucence, Predicine, Bristol-Myers Squibb, EMD Serono, Jazz Therapeutics, Genecentric, Kure it, NCI (R21); Steering committee of studies: Bristol-Myers Squibb, Bavarian Nordic, Seattle Genetics, QED, G1 Therapeutics (all unpaid), and AstraZeneca, EMD Serono, Debiopharm (paid); Data safety monitoring committee: Mereo; Spouse employed by Myriad; Writing/Editor fees: Uptodate, Elsevier Practice Update Bladder Cancer Center of Excellence; Speaking fees: Physicians Education Resource (PER), Onclive, Research to Practice, Medscape, Cancer Network, Masters Lecture Series (MLS). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Disclaimer

The views expressed here are those of the authors and do not necessarily reflect the views of the National Cancer Institute, the National Institutes of Health, the Department of Health and Human Services, or the United States government.

Additional information

Funding

This paper was not funded.