Integrating the immune microenvironment of prostate cancer induced bone disease

Abstract

Prostate cancer (PCa) is the most frequently diagnosed cancer for men in the U.S. but does not impede patient survival until the disease is metastatic. Metastatic lesions most frequently occur in the bone, which exhibits a distinct microenvironment of immune and bone cell populations. Advances in the diagnosis and treatment of primary PCa allow for the use of tailored therapeutic approaches based on biomarkers, protein expression, and histopathology. Understanding the molecular and cellular characteristics of primary tumors has advanced therapeutic development and survival for patients with PCa.Personalized medicine has only recently emerged for the treatment of metastatic bone lesions. Tumor induced bone disease (TIBD) in patients with PCa can be classified into lytic, blastic, or mixed pathologies, with most patients exhibiting the blastic phenotype.Progress has been made in treating TIBD, but metastatic PCa has yet to be cured. Immune checkpoint inhibitors have exhibited limited responses in immunosuppressivePCa tumors, but have yet to be assessed in metastatic sites which may be susceptible to an increased inflammatory response. Recent discoveries have uncovered distinct tumor microenvironments (TMEs) of blastic and lytic bone metastases from patients with PCa, identifying actionable targets for therapeutic applications, including immune checkpoint inhibitors and targeted therapeutics. Enrichment for macrophages and T cells in patient samples suggests metastatic sites may be reappraised as immunologically targetable, despite their immunologically "cold" primary tumors. The practice of performing bone biopsies will help identify unique cellular and protein targets in the bone TME that can guide therapy decisions. K E Y W O R D S bone metastasis, immmunotherapy, prostate cancer, tumor microenvironment 1 | PROSTATE CANCER 1.1 | Scope of prostate cancer Prostate cancer (PCa) is the most commonly diagnosed cancer for men in the U.S., accounting for more than one in five new cancer diagnoses. 1 Thanks to early diagnosis and effective treatment options, survival is extremely high at >99% for localized and regional tumors. 2 Of the 191 930 estimated new cases of PCa in the U.S. for 2020, only 33 330 patients are expected to succumb to the disease. 1 However, once distant metastases are present patient with PCa survival drops to 30%, as patients face fewer therapeutic

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“…S3 c) 17 , which may be related to the lower infiltration of immune cells in the cancer tissue, when compared with adjacent normal liver tissue 40 . Similarly, PARD and PAAD were classified as immunologically “cold” with low immune cell infiltration 41 , 42 , which may contribute to the low cancerous ACE2 expression (Fig. 3 h and Fig.…”

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