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Open Access 01-12-2022 | Prostate Cancer | Research

Differential regulation of TNFα and IL-6 expression contributes to immune evasion in prostate cancer

Authors: Ida Deichaite, Timothy J. Sears, Leisa Sutton, Daniel Rebibo, Kylie Morgan, Tyler Nelson, Brent Rose, Pablo Tamayo, Napoleone Ferrara, Fotis Asimakopoulos, Hannah Carter

Published in: Journal of Translational Medicine | Issue 1/2022

Abstract

Background

The role of the inflammatory milieu in prostate cancer progression is not well understood. Differences in inflammatory signaling between localized and metastatic disease may point to opportunities for early intervention.

Methods

We modeled PCa disease progression by analyzing RNA-seq of localized vs. metastatic patient samples, followed by CIBERSORTx to assess their immune cell populations. The VHA CDW registry of PCa patients was analyzed for anti-TNF clinical outcomes.

Results

We observed statistically significant opposing patterns of IL-6 and TNFα expression between localized and metastatic disease. IL-6 was robustly expressed in localized disease and downregulated in metastatic disease. The reverse was observed with TNFα expression. Metastatic disease was also characterized by downregulation of adhesion molecule E-selectin, matrix metalloproteinase ADAMTS-4 and a shift to M2 macrophages whereas localized disease demonstrated a preponderance of M1 macrophages. Treatment with anti-TNF agents was associated with earlier stage disease at diagnosis.

Conclusions

Our data points to clearly different inflammatory contexts between localized and metastatic prostate cancer. Primary localized disease demonstrates local inflammation and adaptive immunity, whereas metastases are characterized by immune cold microenvironments and a shift towards resolution of inflammation and tissue repair. Therapies that interfere with these inflammatory networks may offer opportunities for early intervention in monotherapy or in combination with immunotherapies and anti-angiogenic approaches.

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Title: Differential regulation of TNFα and IL-6 expression contributes to immune evasion in prostate cancer
Authors: Ida Deichaite
Timothy J. Sears
Leisa Sutton
Daniel Rebibo
Kylie Morgan
Tyler Nelson
Brent Rose
Pablo Tamayo
Napoleone Ferrara
Fotis Asimakopoulos
Hannah Carter
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Prostate Cancer
Prostate Cancer
Bevacizumab
Published in: Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-022-03731-x

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