Analysis of the Correlation between Immunogenomic Phenotype and Patient Outcomes in Prostate Cancer

Although early-stage prostate cancer remains a good response to standard therapies, there are few treatment options for advanced stages or recurrent prostate cancer. Immunotherapy is currently the standard treatment for many types of cancers. However, immune checkpoint-based treatment showed disappointing outcomes in prostate cancer so far, suggesting that the prostate cancer has a potent immunosuppressive microenvironment. Since the tumor infiltrating immune cells are major components of tumor microenvironment, here, we analyzed cellular fractions of the immune cells and investigated if the tumor immune infiltrates are predictors for the prognosis in prostate cancer. The cellular compositions of ten immune cells in prostate cancers were analyzed by using QuanTIseq and EPIC software base on the TCGA mRNA sequencing data. Prostate cancer had the lowest percentage of immune infiltrates compared to other cancers. Moreover, compared to immunotherapy well-responded cancers, such as melanoma, colorectal adenocarcinoma, and non-small cell lung cancer, prostate cancer had significant higher level of M2-liked macrophage and M2 / M1 ratio. We found that the patient progression-free survival was not affected by the infiltration of individual immune cells in prostate cancer; however, patients with a lower M2 / M1 ratio but a higher total number of CD4 T cell, CD8 T cells, and dendritic cell had a significantly better patient progression-free survival. Thorsson et. al. identified six immune subtypes base on immunogenomic analysis across 33 cancers. Most of prostate cancer were clustered in subtypes C1, C2, C3 and C4. Patients from subtype C3 had a significantly better prognosis than patient from subtype C4. Furthermore, the composition of immune infiltrates of subtype C3 tumors were distinct from subtype C4 tumors. Our results demonstrated that the immune infiltrates can be a prognosis maker for prostate cancer. Our study also provides a conceptual framework which addresses the interactions between tumor cells and immune cells in the tumor immune microenvironment of prostate cancer. The framework aims to support future designs of combined treatment to improve immunotherapy in prostate cancer.