Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma
Tumor-associated macrophages remodeling EMT and predicting survival in colorectal carcinoma
复制标题
肿瘤相关巨噬细胞重塑 EMT 并预测结直肠癌生存
DOI：
10.1080/2162402x.2017.1380765
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发表时间：
2018-01-01
期刊：
影响因子：
7.2
通讯作者：
Lai, Maode
中科院分区：
文献类型：
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作者：
Li, Si;Xu, Fangying;Lai, Maode
免疫环境是肿瘤微环境的组成部分，在肿瘤干细胞（CSC）和上皮-间质转化（EMT）中起着重要作用，对肿瘤的发生、发展和预后有着重要影响。肿瘤相关巨噬细胞（Tumor-associated macrophages，TAMs）在免疫环境中含量丰富，但其在CSC、EMT及结直肠癌（colorectal cancer，CRC）预后中的作用尚未阐明。应用免疫组化方法检测419例大肠癌组织中肿瘤中心（TC）和肿瘤浸润前沿（TF）的免疫细胞类型（CD 68（+）巨噬细胞、CD 3（+）、CD 4（+）或CD 8（+）T淋巴细胞、CD 20（+）B淋巴细胞）、EMT标志物（E-cadherin和Snail）和干细胞标志物（CD 44 v6）。还对代表EMT表型的肿瘤芽进行计数。结果发现，大肠癌中浸润最多的免疫细胞为CD 68（+）巨噬细胞。通过相关分析，更多的CD 68（TF）（+）巨噬细胞与更多的CD 44 v6表达（p < 0.001）、更低的Snail（TF）表达（p = 0.08）和更少的肿瘤芽（p < 0.001）相关。更多的CD 68（TF）（+）巨噬细胞与更多的CD 3（TF）（+）T淋巴细胞（p = 0.002）、CD 8（TF）（+）T淋巴细胞（p < 0.001）和CD 20（TF）（+）B淋巴细胞计数（p = 0.004）显著相关。强的CD 68（TF）（+）巨噬细胞浸润也预测长期总生存率。结直肠癌患者中，瘤芽较多者生存率较低。然而，强的CD 68（TF）（+）巨噬细胞浸润可以逆转不利的结果，因为具有更多肿瘤芽但增加的CD 68（TF）（+）巨噬细胞浸润的患者具有有利的结果，类似于较低肿瘤芽组。这项研究提供了直接的形态学证据，表明肿瘤相关的巨噬细胞在侵袭性前沿发挥关键作用，与肿瘤芽的不利结果作斗争，从而为CRC患者带来有利的结局。
The immune contexture, a composition of the tumor microenvironment, plays multiple important roles in cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT), and hence critically influences tumor initiation, progression and patient outcome. Tumor-associated macrophages (TAMs) are abundant in immune contexture, however their roles in CSC, EMT and prognosis of colorectal cancer (CRC) have not been elucidated. In 419 colorectal carcinomas, immune cell types (CD68(+) macrophages, CD3(+), CD4(+) or CD8(+) T lymphocytes, CD20(+) B lymphocytes), EMT markers (E-cadherin and Snail) as well as the stem cell marker (CD44v6) were detected in tumor center (TC) and tumor invasive front (TF) respectively by immunohistochemistry. Tumor buds, that represent EMT phenotype, were also counted. It was found CD68(+) macrophages were the most infiltrating immune cells in CRC. By correlation analysis, more CD68(TF)(+) macrophages were associated with more CD44v6 expression (p < 0.001), lower Snail(TF) expression (p = 0.08) and fewer tumor buds (p < 0.001). More CD68(TF)(+) macrophages were significantly related to more CD3(TF)(+) T lymphocytes (p = 0.002), CD8(TF)(+) T lymphocytes (p < 0.001) and CD20(TF)(+) B lymphocytes counts (p = 0.004). Strong CD68(TF)(+) macrophages infiltration also predicted long term overall survival. CRC patients with more tumor buds had worse survival. However, strong CD68(TF)(+) macrophages infiltration could reverse the unfavorable results since patients with more tumor buds but increasing CD68(TF)(+) macrophages infiltration had the favorable outcome, similar to lower tumor buds groups. This study provided direct morphological evidence that tumor-associated macrophages in the invasive front play critical roles in fighting with the unfavorable results of tumor buds, thus resulting favorable outcomes for CRC patients.