Format

Send to

Choose Destination
Int J Mol Sci. 2019 Apr 13;20(8). pii: E1831. doi: 10.3390/ijms20081831.

Reduced T-cell Numbers and Elevated Levels of Immunomodulatory Cytokines in Metastatic Prostate Cancer Patients De Novo Resistant to Abiraterone and/or Enzalutamide Therapy.

Author information

1
Medical Oncology and Experimental Therapeutics; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. spal@coh.org.
2
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. dmoreira@coh.org.
3
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. haejungw@gmail.com.
4
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. sewhite@coh.org.
5
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. pduttagupta33@gmail.com.
6
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. marclp@stanford.edu.
7
Medical Oncology and Experimental Therapeutics; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. jjones@coh.org.
8
Medical Oncology and Experimental Therapeutics; City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. johsu@coh.org.
9
Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. mkortylewski@coh.org.

Abstract

Currently, there are two Food and Drug Administration (FDA)-approved drugs for androgen deprivation therapy (ADT) of metastatic castration-resistant prostate cancer (mCRPC) patients: abiraterone and enzalutamide. However, our understanding of the effect of these therapies on the immune system in mCRPC patients remains limited. Here, we examined how abiraterone and enzalutamide treatment affects levels of soluble immune mediators in plasma and in circulating immune cells of 44 mCRPC patients. We found that the baseline levels of cytokines fibroblast growth factor (FGF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 10 (IL-10), and IL-6 were significantly lower in ADT-sensitive compared to de novo resistant patients. In addition, resistant patients showed significantly lower T cell frequencies. When comparing the levels of cytokines over the course of treatment, we observed that the levels of proinflammatory mediators, such as interferon-γ (IFN-γ), IL-5, macrophage inflammatory protein 1 alpha (MIP-1α), and tumor necrosis factor alpha (TNFα), were significantly increased in the ADT-sensitive patients. At the same time, the abiraterone/enzalutamide therapy did not reduce the percentage of tolerogenic myeloid cell populations, such as polymorphonuclear myeloid-derived suppressor cells, which retained unaltered expression of programmed death-ligand 1 (PD-L1) and B7-H3. Overall, our results suggest that certain immune markers, such as IL-6 and the frequency of effector T cells, could be predictive of therapeutic response to ADT therapies in mCRPC patients.

KEYWORDS:

ADT; CRPC; abiraterone; castration-resistant prostate cancer; cytokines; enzalutamide

PMID:
31013891
DOI:
10.3390/ijms20081831
Free full text

Supplemental Content

Full text links

Icon for Multidisciplinary Digital Publishing Institute (MDPI)
Loading ...
Support Center