The reactive stroma response regulates the immune landscape in prostate cancer

Abstract

Prostate cancer remains the most commonly diagnosed and the second leading cause of cancer-related deaths in men in the United States. The neoplastic transformation of prostate epithelia, concomitant with modulations in the stromal compartment, known as reactive stromal response, is critical for the growth, development, and progression of prostate cancer. Reactive stroma typifies an emergent response to disrupted tissue homeostasis commonly observed in wound repair and pathological conditions such as cancer. Despite the significance of reactive stroma in prostate cancer pathobiology, our understanding of the ontogeny, phenotypic and functional heterogeneity, and reactive stromal regulation of the immune microenvironment in prostate cancer remains limited. Traditionally characterized to have an immunologically "cold" tumor microenvironment, prostate cancer presents significant challenges for advancing immunotherapy compared to other solid tumors. This review explores the detrimental role of reactive stroma in prostate cancer, particularly its immunomodulatory function. Understanding the molecular characteristics and dynamic transcriptional program of the reactive stromal populations in tandem with tumor progression could offer insights into enhancing immunotherapy efficacy against prostate cancer.