The tumor microenvironment and immune responses in prostate cancer patients

Abstract

The landscape of cancer treatment has been transformed over the past decade by the success of immune-targeting therapies. However, despite sipuleucel-T being the first ever approved vaccine for cancer and the first immunotherapy licensed for prostate cancer in 2010, immunotherapy has since seen limited success in the treatment of prostate cancer. The tumour microenvironment of prostate cancer presents particular barriers for immunotherapy. Moreover, prostate cancer is distinguished by being one of only two solid tumours where increased T cell infiltration correlates with a poorer, rather than improved, outlook. Here, we discuss the specific aspects of the prostate cancer microenvironment that converge to create a challenging microenvironment, including myeloid-derived immune cells and cancer-associated fibroblasts. By exploring the immune microenvironment of defined molecular subgroups of prostate cancer, we propose an immunogenomic subtyping approach to single-agent and combination immune targeting strategies that could improve outcomes in prostate cancer treatment.

Epithelial–Mesenchymal Transition Signaling and Prostate Cancer Stem Cells: Emerging Biomarkers and Opportunities for Precision Therapeutics

“…There is a strong association between reduced expression of E-cadherin and membranous β-catenin and progression in various types of carcinomas, including PCa, which could be used as a prognostic biomarker [21]. Prostate tumors are also able to interact with supporting extracellular matrix and stromal elements to establish a pro-tumorigenic immunosuppressive TME [14,22]. Tumors undergoing EMT may express intermediate morphological, transcriptional, and epigenetic features, that range across the spectrum of epithelial and mesenchymal markers [23].…”

“…There is a strong association between reduced expression of E-cadherin and membranous β-catenin and progression in various types of carcinomas, including PCa, which could be used as a prognostic biomarker [ 21 ]. Prostate tumors are also able to interact with supporting extracellular matrix and stromal elements to establish a pro-tumorigenic immunosuppressive TME [ 14 , 22 ].…”

“…Prostate tumors interact closely with the TME and stromal elements adjacent to tumor cells, which creates an immunosuppressive TME [ 14 , 22 ]. An early study on this topic highlights the role of cancer-associated fibroblast (CAFs) in the TME of PCa.…”

Immunotherapy in Advanced Prostate Cancer—Light at the End of the Tunnel?

“…MDSC are a population of immature myeloid cells that exhibit immune-suppressive effects on T cells and NK cells and therefore are considered to be an important mechanism of immunotherapeutic resistance in PCa (reviewed in [ 66 , 67 ]) ( Figure 1 ). MDSCs promote recruitment of Tregs that suppress the function of CTLs, and can differentiate to monocytes or neutrophils and then further to M2 macrophages, which also inhibits CTL activity [ 68 ]. Consequently, low T cell recruitment and reduced activity result in inefficacy of immunotherapeutic strategies in PCa.…”

Celebrating the 80th anniversary of hormone ablation for prostate cancer

“…Although the effects of DNA repair defects and genetic/ epigenetic aberrations on the cell division machinery are increasingly well-defined, it has become evident that the tumor microenvironment (TME), including stroma, endothelial and immune cells, plays an important role in prostate cancer disease progression and survival (Hinshaw & Shevde 2019). In this special issue, Kwon, Bryant and Parkes describe the role of immunotherapy in prostate cancer treatment in the article 'The tumor microenvironment and immune responses in prostate cancer' (Kwon et al 2021). Large phase III clinical trials have failed to show improvement in overall survival with ipilimumab (a CTLA-4 inhibitor) (Kwon et al 2014, Beer et al 2017.…”