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

• DOI: 10.20944/preprints202005.0462.v1
• Publication Date: 2020-05-29T06:09:51Z
• Authors: Neil K. Jairath; Mark W. Farha; Sudharsan Srinivasan; Ruple Jairath; Michael D. Green; Robert T. Dess; William C. Jackson; Adam B. Weiner; Edward M. Schaeffer; Shuang G. Zhao; Felix Y. Feng; Issam El Naqa; Daniel E. Spratt
• Keywords: 0301 basic medicine; tumor immune microenvironment; 03 medical and health sciences; immunotherapy; prostate cancer; RNAseq; radiation therapy; plasma cells; Article; oncology_oncogenics; macrophages; 3. Good health

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=496) was utilized. immune microenvironment using the CIBERSORTX tool to identify cell type composition. Unsupervised hierarchical clustering performed based on content. Analyses progression-free survival (PFS), distant metastases, overall (OS) were Kaplan-Meier estimates Cox-regression multivariable analyses. Results: Four clusters identified, largely defined plasma cell, CD4+ Memory Resting T Cells (CD4 MR), M0 M2 macrophage content MRHighPlasma CellHighM0LowM2Low, CD4 MRLowPlasma CellLowM0HighM2Low, CellLowM0LowM2High). two macrophage-enriched/plasma non-enriched (3&4) demonstrated worse PFS (HR 2.24, 95% CI 1.46–3.45, p=0.0002) than 1&2. No metastatic events occurred non-macrophage-enriched clusters. Comparing 3 vs 4, patients treated surgery alone, cluster had zero progression (p<0.0001). However, outcomes after post-operative radiotherapy (p=0.018). Conclusion: Distinct tumor with a macrophage-enriched phenotype reduced enrichment independently characterize an aggressive localized that may differentially respond treatment.