The Roles of Tumor-Associated Macrophages in Prostate Cancer

Abstract

The morbidity of prostate cancer (PCa) is rising year by year, and it has become the primary cause of tumor-related mortality in males. It is widely accepted that macrophages account for 50% of the tumor mass in solid tumors and have emerged as a crucial participator in multiple stages of PCa, with the huge potential for further treatment. Oftentimes, tumor-associated macrophages (TAMs) in the tumor microenvironment (TME) behave like M2-like phenotypes that modulate malignant hallmarks of tumor lesions, ranging from tumorigenesis to metastasis. Several clinical studies indicated that mean TAM density was higher in human PCa cores versus benign prostatic hyperplasia (BPH), and increased biopsy TAM density potentially predicts worse clinicopathological characteristics as well. Therefore, TAM represents a promising target for therapeutic intervention either alone or in combination with other strategies to halt the “vicious cycle,” thus improving oncological outcomes. Herein, we mainly focus on the fundamental aspects of TAMs in prostate adenocarcinoma, while reviewing the mechanisms responsible for macrophage recruitment and polarization, which has clinical translational implications for the exploitation of potentially effective therapies against TAMs.

Osteoid cell-derived chemokines drive bone-metastatic prostate cancer

“…Multiple studies show CCL2 recruits monocytes to BM-PCa tumors and increases the number of tumor-associated osteoclasts, such that CCL2 inhibition decreases tumor-induced bone resorption in mice ( 102 , 103 ). Recruited monocytes were also found to mature into tumor-associated macrophages (TAMs), which promote cancer progression through multiple mechanisms ( 102 , 104 – 106 ), including promotion of tumor proliferation, cancer cell stemness, metastasis, and therapy resistance, while also suppressing anti-tumor immune responses ( 107 – 111 ).…”

Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor‐Associated Macrophages in Prostate Cancer

“…[1] In prostate cancer (PCa), TAMs are major immune cells in the tumor microenvironment to facilitate PCa progression via enhancing PCa cell migration and metastasis, promoting drug resistance, and so on. [2][3][4][5][6] Functionally, TAMs are primarily composed of M2-type macrophages, which can be polarized by various tumor microenvironmental factors such as chemokines, cytokines and tumor-derived extracellular vesicles (EVs). [7,8] Currently, besides their promoting effects on resistance of chemotherapy and immunotherapy, TAMs are reported to be also involved in the resistance of ferroptosis by secretion of transforming growth factor beta 1.…”

“…[ 1 ] In prostate cancer (PCa), TAMs are major immune cells in the tumor microenvironment to facilitate PCa progression via enhancing PCa cell migration and metastasis, promoting drug resistance, and so on. [ 2–6 ] Functionally, TAMs are primarily composed of M2‐type macrophages, which can be polarized by various tumor microenvironmental factors such as chemokines, cytokines and tumor‐derived extracellular vesicles (EVs). [ 7,8 ]…”

Targeting the αVβ3/NgR2 pathway in neuroendocrine prostate cancer

“…The cross-talk between cancer cells and tumor microenvironment (TME) components, such as immune cells, fibroblasts, and endothelial cells, is well established [ 41 , 42 ]. In particular, tumor-associated macrophages (TAMs), derived from resident macrophages and newly recruited monocytes, represent the major constituents of the TME [ 43 , 44 ].…”

“…Two phenotypes of TAMs are commonly recognized: classically activated M1 and alternatively activated M2. M1 are pro-inflammatory and anti-tumoral, and are characterized by the surface expression of CD80, CD86, and HLA-DR. M2 exert an immunosuppressive and pro-tumorigenic activity, and their main surface markers are CD206, CD163, and CD204 [ 42 , 44 – 46 ]. Although this dichotomy has been acknowledged as an over-simplification, an imbalance between M1 and M2 in favor of M2 in the TME, appears to be associated with tumor growth, angiogenesis, and metastasis [ 42 , 47 , 48 ].…”