Prostate cancer is a significant global health issue and limitations to current patient management pathways often result in over- or under-treatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow utilizing an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA-Seq, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA-seq in 27/27 cases and a significantly higher TIL count was noted in tumors without a TMPRSS2:ERG fusion compared to those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n=436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-High and TIL-Low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1/27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion positive tumors. Detailed profiling, as shown here, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort.