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 lead to improved outcomes in prostate cancer treatment.
Highlights
Prostate cancer (PCa) is the second most commonly diagnosed cancer and the fifth most common cause of death in men worldwide (Sung et al 2021)
Whilst many cases of low-risk volume PCa may be managed by active surveillance and not need immediate treatment, clinically significant localised and locally advanced PCa may be treated with curative intent by surgery or radiotherapy with concomitant androgen deprivation therapy (ADT)
PCa appears to adjust to neutrophils over time with neutrophil cytotoxicity being gradually abrogated, correlating with prolonged neutrophil viability and diminished neutrophil extracellular trap formation (Costanzo-Garvey et al 2020). These findings suggest that neutrophils may be able to combat the development of PCa metastases in bone, but caution must be exercised when devising therapies targeting these cells given the temporal dynamics of neutrophil effector function in the tumour microenvironment (TME)
Summary
Prostate cancer (PCa) is the second most commonly diagnosed cancer and the fifth most common cause of death in men worldwide (Sung et al 2021). The aetiology of PCa is multifactorial, genomics is a key variable underpinning the development of this malignancy. Metaanalysis of genome-wide association data depicted an increase in incidence of PCa in men of African ancestry and the estimated lifetime risk of developing PCa is compounded by a positive familial history (Conti et al 2021). Whilst many cases of low-risk volume PCa may be managed by active surveillance and not need immediate treatment, clinically significant localised and locally advanced PCa may be treated with curative intent by surgery or radiotherapy with concomitant androgen deprivation therapy (ADT). Advanced-stage disease in most cases develops resistance to ADT, underscoring the unmet clinical need to develop new treatments for metastatic castration-resistant PCa (mCRPC).
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