scholarly journals Downregulation of LOX promotes castration-resistant prostate cancer progression via IGFBP3

2021 ◽  
Vol 12 (24) ◽  
pp. 7349-7357
Author(s):  
Xuanrong Chen ◽  
Yi Shao ◽  
Wanqing Wei ◽  
Haishan Shen ◽  
Yang Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Activation of GRP/GRP-R signaling contributes to castration-resistant prostate cancer progression

Oncotarget ◽  
2016 ◽  
Vol 7 (38) ◽  
pp. 61955-61969 ◽  
Author(s):  
Jingbo Qiao ◽  
Magdalena M. Grabowska ◽  
Ingrid S. Forestier-Roman ◽  
Janni Mirosevich ◽  
Thomas C. Case ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Castration-mediated IL-8 Promotes Myeloid Infiltration and Prostate Cancer Progression

2019 ◽  
Author(s):  
Zoila A. Lopez-Bujanda ◽  
Michael C. Haffner ◽  
Matthew G. Chaimowitz ◽  
Nivedita Chowdhury ◽  
Nicholas J. Venturini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Suppressor Cells ◽  
Immune Checkpoint Blockade ◽  
Prostate Cancer Progression ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Intrinsic Factors ◽  
Castration Resistant ◽  
Clinical Responses

SummaryImmunotherapy is a treatment for many types of cancer, primarily due to deep and durable clinical responses mediated by immune checkpoint blockade (ICB)1, 2. Prostate cancer is a notable exception in that it is generally unresponsive to ICB. The standard treatment for advanced prostate cancer is androgen-deprivation therapy (ADT), a form of castration (CTX). ADT is initially effective, but over time patients eventually develop castration-resistant prostate cancer (CRPC). Here, we focused on defining tumor-cell intrinsic factors that contribute to prostate cancer progression and resistance to immunotherapy. We analyzed cancer cells isolated from castration-sensitive and castration-resistant prostate tumors, and discovered that castration resulted in significant secretion of Interleukin-8 (IL-8) and it’s likely murine homolog Cxcl15. These chemokines drove subsequent intra-tumoral infiltration with polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), promoting tumor progression. PMN-MDSC infiltration was abrogated when IL-8 was deleted from prostate cancer epithelial cells using CRISPR/Cas9, or when PMN-MDSC migration was blocked with antibodies against the IL-8 receptor CXCR2. Blocking PMN-MDSC infiltration in combination with anti-CTLA-4 delayed the onset of castration resistance and increased the density of polyfunctional CD8 T cells in tumors. Taken together, our findings establish castration-mediated IL-8 secretion and subsequent PMN-MDSC infiltration as a key suppressive mechanism in the progression of prostate cancer. Targeting of the IL-8/CXCR2 axis around the time of ADT, in combination with ICB, represents a novel therapeutic approach to delay prostate cancer progression to advanced disease.

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