Immunome profiling in prostate cancer: a guide for clinicians

Abstract

Tumor immune microenvironment (TIME) plays a key role to understand how tumors respond to prostate cancer (PC) therapies and potential mechanisms of resistance. Previous research has suggested that specific genomic aberrations, such as microsatellite instability (MSI) or CDK12 bi-allelic loss can allow PC patients more likely to respond to immune checkpoint inhibitors (ICI) or other immune therapies. However, responses to these treatments remain highly variable even in selected patients. Thus, it is essential to obtain more information about tumor immune cells that infiltrate these tumors, and on their plasticity and interactions, in order to better understand the underlying biology to allow development of new therapeutic strategies. This review analyzes: 1) How interactions among immune cell populations and other cells infiltrating the tumor stroma can modulate the progression of PC, 2) How the standard therapies to treat PC (such as androgen deprivation therapy, new androgen-directed hormone therapy or chemotherapy) may influence the dynamic changes of the immunome and 3) What are the limitations in characterizing the immune landscape of the host´s response to tumors.

Keywords: biomarkers; immunome; immunophenotype; immunotherapy; prostate cancer.

Figure 1

Immune microenvironment in prostate cancer (PC). This figure shows the main features that characterize tumor immune microenvironment in primary PC niche. CAF, Cancer-associated fibroblasts; DC, Dendritic cell; M1, Classically activated macrophages; M2, Alternatively activated macrophages; MDSC, Myeloid-derived suppressor cells; NK, Natural killer cell; TIL, Tumor infiltrating lymphocytes. Created with Biorender.com.

Figure 2

Technical approaches to analyze antitumor immune response. The chart summarizes the main characteristics of the techniques used in the study of the TIME in PC, with either peripheral blood or tumor samples. Created with Biorender.com.