Department of Operative Gynecology and Gynecologic Oncology, Polish Mother's Memorial Hospital-Research Institute, 93-338 Lodz, Poland.
Institute of Medical Biology, Polish Academy of Sciences, 93-232 Lodz, Poland.
Cells. 2020 May 22;9(5):1299. doi: 10.3390/cells9051299.
Tumor-associated macrophages (TAMs) constitute the main population of immune cells present in the ovarian tumor microenvironment. These cells are characterized by high plasticity and can be easily polarized by colony-stimulating factor-1, which is released by tumor cells, into an immunosuppressive M2-like phenotype. These cells are strongly implicated in both the progression and chemoresistance of ovarian cancer. The main pro-tumoral function of M2-like TAMs is the secretion of a variety of cytokines, chemokines, enzymes and exosomes that reach microRNAs, directly inducing the invasion potential and chemoresistance of ovarian cancer cells by triggering their pro-survival signaling pathways. The M2-like TAMs are also important players in the metastasis of ovarian cancer cells in the peritoneum through their assistance in spheroid formation and attachment of cancer cells to the metastatic area-the omentum. Moreover, TAMs interplay with other immune cells, such as lymphocytes, natural killer cells, and dendritic cells, to inhibit their responsiveness, resulting in the development of immunosuppression. The detrimental character of the M2-like type of TAMs in ovarian tumors has been confirmed by a number of studies, demonstrating the positive correlation between their high level in tumors and low overall survival of patients.
肿瘤相关巨噬细胞(TAMs)构成了卵巢肿瘤微环境中存在的主要免疫细胞群体。这些细胞具有很高的可塑性,很容易被肿瘤细胞释放的集落刺激因子-1(CSF-1)极化,形成一种免疫抑制的 M2 样表型。这些细胞强烈参与卵巢癌的进展和化疗耐药。M2 样 TAMs 的主要促肿瘤功能是分泌各种细胞因子、趋化因子、酶和外泌体,这些物质可以直接到达 microRNAs,通过触发其促生存信号通路,直接诱导卵巢癌细胞的侵袭潜力和化疗耐药性。M2 样 TAMs 也是卵巢癌细胞在腹膜中转移的重要参与者,通过协助球体形成和癌细胞附着在转移区域(网膜)来实现这一功能。此外,TAMs 与其他免疫细胞(如淋巴细胞、自然杀伤细胞和树突状细胞)相互作用,抑制其反应性,导致免疫抑制的发展。大量研究证实了 M2 样 TAMs 在卵巢肿瘤中的有害特征,表明它们在肿瘤中的高水平与患者总体生存率降低之间存在正相关关系。