Colorectal cancer (CRC) is a major global health burden and a leading cause of cancer-related mortality, with metastasis representing the primary cause of death. Angiogenesis plays a critical role in this process, and macrophages within the tumor microenvironment (TME) are its key regulators. Among these, Tie2-expressing macrophages (TEMs) constitute a distinct pro-angiogenic subset that localizes to perivascular regions and responds to angiopoietin2 (Ang2) signaling. Moreover, TEMs contribute to vessel destabilization and the formation of permissive niches for cancer cell intravasation, linking them to both angiogenic and non-angiogenic modes of malignant tumor progression. The significance of TEMs in CRC remains controversial. This controversy, as we noticed, stems from a confluence of methodological challenges, lack of standardized markers, small-scale studies, inconsistent findings across studies, and the inherent complexity of both CRC biology and macrophage biology. Evidence from preclinical models and patient samples highlights the correlation between Ang2/Tie2 activity, TEM infiltration, and poor prognosis in CRC. This review summarizes current knowledge on the role of TEMs and the Ang/Tie2 axis in CRC angiogenesis, metastasis, and resistance to anti-angiogenic therapies. Advancing our understanding of TEMs may enable novel macrophage-focused strategies to inhibit CRC progression and improve patient outcomes.
结直肠癌（CRC）是全球重大健康负担及癌症相关死亡的主要原因，其中转移是导致死亡的首要因素。血管生成在此过程中起着关键作用，而肿瘤微环境（TME）中的巨噬细胞是其核心调控者。其中，表达Tie2的巨噬细胞（TEMs）构成了一类独特的促血管生成亚群，定位于血管周围区域并对血管生成素2（Ang2）信号作出响应。此外，TEMs参与血管失稳及形成利于癌细胞内渗的许可性微环境，从而将其与恶性肿瘤进展的血管生成性和非血管生成性模式联系起来。TEMs在结直肠癌中的重要性仍存在争议。我们注意到，这一争议源于方法学挑战、标准化标志物缺乏、小规模研究、不同研究结果不一致以及结直肠癌生物学和巨噬细胞生物学固有的复杂性等多重因素。临床前模型和患者样本的证据表明，Ang2/Tie2活性、TEM浸润与结直肠癌不良预后之间存在相关性。本综述总结了当前关于TEMs及Ang/Tie2轴在结直肠癌血管生成、转移及抗血管生成治疗耐药中作用的认识。深化对TEMs的理解可能推动以巨噬细胞为靶点的新型策略，以抑制结直肠癌进展并改善患者预后。
肿瘤(癌症)患者之家