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

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 = 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.

Five hypoxia and immunity related genes as potential biomarkers for the prognosis of osteosarcoma

“…Our study found that TRIM8 was negatively correlated with resting mast cells. Similar studies have found that innate and adaptive immune response cells, such as resting mast cells, have extensive connections with the external environment, can release inflammatory mediators and other factors that affect tumor growth, and inhibit cancer progression 28 , 41 . These observations are consistent with those found in our study.…”

Prognostic Value of Intratumoral Lymphocyte-to-Monocyte Ratio and M0 Macrophage Enrichment in Tumor Immune Microenvironment of Melanoma

“…Ultimately, M0s may represent another type of TAM or an incompletely differentiated M2 [ 51 ]. M0 macrophages have been found to be one of the cell subsets most strongly associated with poor outcome in breast cancer [ 53 ], prostate cancer [ 54 ] and lung adenocarcinoma [ 55 ], whereas reduced M0 content has been associated with better prognosis in bladder cancer [ 56 ]. In a comprehensive analysis of digestive system cancers, M0 macrophages were among the most prevalent immune cell fractions, with M0-enriched clusters associated with decreased recurrence-free survival and worse prognostic immune score [ 57 ].…”

Prognostic Value of the Intratumoral Lymphocyte to Monocyte Ratio and M0 Macrophage Enrichment in the Melanoma Immune Microenvironment

“…may represent another type of TAM or an incompletely differentiated M2 [47]. M0 macrophages were found to be one of the cell subsets most strongly associated with poor outcome in breast cancer [49], prostate cancer [50], and lung adenocarcinoma [51], while reduced M0 content has been associated with better prognosis in bladder cancer [52]. In a comprehensive analysis Interleukin-10 is an immunosuppressive cytokine produced mainly by monocytes.…”