Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Res. 2023 Jan 4;83(1):3-11. doi: 10.1158/0008-5472.CAN-22-1403.
Tumor-associated macrophages (TAM) play an important role in supporting tumor growth and suppressing antitumor immune responses, and TAM infiltration has been associated with poor patient prognosis in various cancers. TAMs can be classified as pro-inflammatory, M1-like, or anti-inflammatory, M2-like. While multiple factors within the tumor microenvironment affect the recruitment, polarization, and functions of TAMs, accumulating evidence suggests that Wnt signaling represents an important, targetable driver of an immunosuppressive, M2-like TAM phenotype. TAM production of Wnt ligands mediates TAM-tumor cross-talk to support cancer cell proliferation, invasion, and metastasis. Targeting TAM polarization and the protumorigenic functions of TAMs through inhibitors of Wnt signaling may prove a beneficial treatment strategy in cancers where macrophages are prevalent in the microenvironment.
肿瘤相关巨噬细胞（TAM）在支持肿瘤生长和抑制抗肿瘤免疫反应方面发挥着重要作用，TAM 的浸润与各种癌症患者的不良预后相关。TAM 可以分为促炎型、M1 样，或抗炎型、M2 样。虽然肿瘤微环境中的多种因素会影响 TAM 的募集、极化和功能，但越来越多的证据表明 Wnt 信号代表了一种重要的、可靶向的免疫抑制性、M2 样 TAM 表型的驱动因素。TAM 产生的 Wnt 配体介导 TAM-肿瘤的串扰，以支持癌细胞的增殖、侵袭和转移。通过 Wnt 信号抑制剂靶向 TAM 极化和 TAM 的促肿瘤功能，可能成为微环境中巨噬细胞丰富的癌症的一种有益的治疗策略。
