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Immune Modulation in Prostate Cancer Patients Treated with Androgen Receptor (AR)-Targeted Therapy
Open AccessArticle

Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-Enriched Subtypes

1
Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48104, USA
2
Department of Urology, Northwestern University, Chicago, IL 60611, USA
3
Department of Radiation Oncology, UCSF, San Francisco, CA 94143, USA
4
Veterans Affair Ann Arbor Healthcare System, University of Michigan, Ann Arbor, MI 48104, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this manuscript.
J. Clin. Med. 2020, 9(6), 1973; https://doi.org/10.3390/jcm9061973
Received: 27 May 2020 / Revised: 11 June 2020 / Accepted: 23 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue Advances in the Diagnosis and Treatment for Prostate Cancer)
Background: Prostate cancer (PCa) is characterized by significant heterogeneity in its molecular, genomic, and immunologic characteristics. Methods: Whole transcriptome RNAseq data from The Cancer Genome Atlas of prostate adenocarcinomas (n = 492) was utilized. The immune microenvironment was characterized using the CIBERSORTX tool to identify immune cell type composition. Unsupervised hierarchical clustering was performed based on immune cell type content. Analyses of progression-free survival (PFS), distant metastases, and overall survival (OS) were performed using Kaplan–Meier estimates and Cox regression multivariable analyses. Results: Four immune clusters were identified, largely defined by plasma cell, CD4+ Memory Resting T Cells (CD4 MR), and M0 and M2 macrophage content (CD4 MRHighPlasma CellHighM0LowM2Mid, CD4 MRLowPlasma CellHighM0LowM2Low, CD4 MRHighPlasma CellLowM0HighM2Low, and CD4 MRHighPlasma CellLowM0LowM2High). The two macrophage-enriched/plasma cell non-enriched clusters (3 and 4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p = 0.0002) than the clusters 1 and 2. No metastatic events occurred in the plasma cell enriched, non-macrophage-enriched clusters. Comparing clusters 3 vs. 4, in patients treated by surgery alone, cluster 3 had zero progression events (p < 0.0001). However, cluster 3 patients had worse outcomes after post-operative radiotherapy (p = 0.018). Conclusion: Distinct tumor immune clusters with a macrophage-enriched, plasma cell non-enriched phenotype and reduced plasma cell enrichment independently characterize an aggressive phenotype in localized prostate cancer that may differentially respond to treatment. View Full-Text
Keywords: prostate cancer; immunotherapy; radiation therapy; macrophages; RNAseq; tumor immune microenvironment; plasma cells prostate cancer; immunotherapy; radiation therapy; macrophages; RNAseq; tumor immune microenvironment; plasma cells
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Jairath, N.K.; Farha, M.W.; Srinivasan, S.; Jairath, R.; Green, M.D.; Dess, R.T.; Jackson, W.C.; Weiner, A.B.; Schaeffer, E.M.; Zhao, S.G.; Feng, F.Y.; El Naqa, I.; Spratt, D.E. Tumor Immune Microenvironment Clusters in Localized Prostate Adenocarcinoma: Prognostic Impact of Macrophage Enriched/Plasma Cell Non-Enriched Subtypes. J. Clin. Med. 2020, 9, 1973.

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