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Background: Tumor-associated macrophages (TAMs) are critical components of the tumor microenvironment (TME) in prostate cancer. Commonly used orthotopic models do not accurately reflect the complete TME of a human patient or the natural initiation and progression of a tumor. Therefore, genetically engineered mouse models are essential for studying the TME as well as advancing TAM-targeted therapies. Two common transgenic (TG) models of prostate cancer are Hi-Myc and transgenic adenocarcinoma of the mouse prostate (TRAMP), but the TME and TAM characteristics of these models have not been well characterized., Methods: To advance the Hi-Myc and TRAMP models as tools for TAM studies, macrophage infiltration and characteristics were assessed using histopathologic, flow cytometric, and expression analyses in these models at various timepoints during tumor development and progression., Results: In both Hi-Myc and TRAMP models, macrophages adopt a more pro-tumor phenotype in higher histological grade tumors and in older prostate tissue. However, the Hi-Myc and TRAMP prostates differ in their macrophage density, with Hi-Myc tumors exhibiting increased macrophage density and TRAMP tumors exhibiting decreased macrophage density compared to age-matched wild type mice., Conclusions: The macrophage density and the adenocarcinoma cancer subtype of Hi-Myc appear to better mirror patient tumors, suggesting that the Hi-Myc model is the more appropriate in vivo TG model for studying TAMs and TME-targeted therapies., (© 2021 The Authors. The Prostate published by Wiley Periodicals LLC.)

Purpose of Review: This review aims to highlight recent advances in prostate cancer tumor-immune microenvironment research and summarize the state-of-the-art knowledge of immune checkpoint inhibitors in prostate cancer., Recent Findings: Immune checkpoint inhibitors are the cornerstone of modern immunotherapy which have shown encouraging results across a spectrum of cancers. However, only limited survival benefit has been seen in patients with prostate cancer. Prostate cancer progression and its response to immunotherapies are strongly influenced by the tumor-immune microenvironment, whose feature can be summarized as low amounts of tumor-specific antigens, low frequency of tumor-infiltrating lymphocytes and high frequency of tumor-associated macrophages. To improve the therapeutic effect of immunotherapies, in recent years, many strategies have been applied, of which the most promising ones include the combination of multiple immunotherapeutic agents, the combination of an immunotherapeutic agent with other modalities in parallel or in sequential, and the development of biomarkers to find a subgroup of patients who may benefit the most from immunotherapeutic agents., Summary: The impact of immune content and specific immune cell types on prostate cancer biology is highly complex. Recent clinical trials have shed light on the optimal use of immunotherapies for prostate cancer., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)