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

2. Zero hunger 0301 basic medicine tumor immune microenvironment 0303 health sciences prostate cancer RNAseq radiation therapy plasma cells Article macrophages 3. Good health 03 medical and health sciences immunotherapy oncology_oncogenics
DOI: 10.20944/preprints202005.0462.v1 Publication Date: 2020-05-29T06:09:51Z
ABSTRACT
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.
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