TME profiling in Colombian men with suspected prostate cancer

Prostate cancer (PCa) features a heterogeneous tumor microenvironment (TME) that shapes evolution and therapeutic response. Although immune and stromal composition have emerged as source of prognostic biomarkers, these components remain poorly characterized in Latin American populations. No previous study has integrated computational immune deconvolution with in situ validation in this context. We aimed to define TME remodeling across malignant, adjacent, and benign prostate tissue in a Colombian cohort.RNA-seq data from 75 patients with suspected PCa were TMM-normalized and analyzed using differential expression models adjusted for PSA, age, and Gleason grade. Immune composition and stromal enrichment were inferred using CIBERSORT and xCell. For validation, six TMAs were constructed from 20 prostatectomy patients: five TMAs included three PCa-positive cases each (Gleason grades 3+3, 3+4, 4+3, 4+4, 4+5) sampling tumor and adjacent tissue, and one TMA contained benign tissue from five PCa-negative cases. IHC quantified CD8⁺ T-cell and CD11b⁺ myeloid infiltration.Deconvolution revealed distinct immune shifts between malignant and benign tissue. PCa-positive samples showed significant enrichment of M1 macrophages (p=0.02), plasmacytoid dendritic cells (p<0.001), and Th1 cells (p=0.0075), alongside elevated stromal scores (p=0.0014), indicating a predominantly inflammatory TME. In contrast, PCa-negative samples displayed higher mast cells, hematopoietic stem cells, common myeloid progenitors (all p<0.0001), NK cells (p=0.0009), CD8⁺ effector memory T cells (p=0.0006), and CD4⁺ naïve T cells (p=0.0047), consistent with an immunologically quiescent state. IHC validation confirmed increased CD8⁺ T-cell infiltration in tumor versus adjacent (p<0.001) and benign tissue (p=0.016), and higher CD11b⁺ myeloid infiltration versus adjacent (p=0.002) and benign tissue (p=0.040). Critically, CD11b⁺ infiltration correlated with Gleason grade, while CD8⁺ infiltration remained elevated across all grades.This study provides the first multimodal TME profiling in a Colombian PCa cohort. Integration of RNA-seq deconvolution with TMA-based IHC reveals immune remodeling characterized by enrichment of cytotoxic T cells and myeloid populations in malignant tissue. The grade-dependent CD11b⁺ infiltration suggests potential as a stratification biomarker for immunotherapy and supports therapeutic targeting of myeloid cells in underrepresented populations.