High macrophage infiltration along the tumor front correlates with improved survival in colon cancer
High macrophage infiltration along the tumor front correlates with improved survival in colon cancer
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DOI：
10.1158/1078-0432.ccr-06-2073
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发表时间：
2007-03-01
影响因子：
11.5
通讯作者：
Palmqvist, Richard
中科院分区：
文献类型：
--
作者：
Forssell, Johan;Oeberg, Ake;Palmqvist, Richard
目的：巨噬细胞在肿瘤发生中的作用是复杂的，因为它们可以防止和促进肿瘤development.Experimental Design：四百四十六个结直肠癌标本染色的泛单核细胞/巨噬细胞标记物CD 68，和平均浸润沿着肿瘤前沿进行了半定量评估，使用四级量表。对于CD 68热点的存在，对每个切片进行类似评分。巨噬细胞-肿瘤细胞相互作用的一些方面也进行了研究，使用在体外coculturesystem.Results：包括所有患者，无论手术结果和定位，生存率增加递增与CD 68 TF（平均）浸润等级（P = 0.0001），但不是在根治性切除结肠癌（P = 0.28）。CD 68热点评分（CD 68 TF（Hotspot））分为高、低两组。高热点评分在结肠癌根治性切除病例中也具有高度显著的生存优势（n = 199，P = 0.0002），但在直肠癌中没有。在多变量分析中，包括性别、年龄、定位、分级、分期、肿瘤类型和肿瘤前沿淋巴细胞，CD 68 TF（Hotpot）高被证明是结肠癌的独立预后标志物，相对风险为0.49（P = 0.007）。在体外共培养实验中，使用佛波醇12-肉豆蔻酸酯13 -乙酸酯活化的U937细胞作为巨噬细胞模型，揭示了巨噬细胞与结肠癌细胞的高比率抑制癌细胞生长。这是部分依赖于细胞与细胞的接触，而Boyden室共培养没有细胞与细胞的接触促进癌细胞spread.Conclusions：总之，我们的数据表明，一个致密的巨噬细胞浸润在肿瘤的正面积极影响结肠癌的预后和细胞与细胞的接触程度可能会影响之间的平衡protumorigenic和抗肿瘤的性质的巨噬细胞。
Purpose: The role of macrophages in tumorigenesis is complex because they can both prevent and promote tumor development.Experimental Design: Four hundred forty-six colorectal cancer specimens were stained with the pan-monocyte/macrophage marker CD68, and average infiltration along the tumor front was semiquantitatively evaluated using a four-grade scale. Each section was similarly scored for the presence of CD68 hotspots. Some aspects of macrophage-tumor cell interactions were also studied using in vitro coculture systems.Results: Including all patients, regardless of surgical outcome and localization, survival increased incrementally with CD68TF(Mean) infiltration grade (P = 0.0001) but not in curatively resected colon cancers (P = 0.28). CD68 hotspot score (CD68TF(Hotspot)) was divided into high and low. A high hotspot score conferred a highly significant survival advantage also in curatively resected colon cancer cases (n = 199, P = 0.0002) but not in rectal cancers. CD68TF(Hotpot) high turned out as an independent prognostic marker for colon cancer in multivariate analyses including gender, age, localization, grade, stage, tumor type, and lymphocytes at the tumor front, conferring a relative risk of 0.49 (P = 0.007). In vitro coculture experiments, using phorbol 12-myristate 13 - acetate -activated U937 cells as macrophage model, revealed that a high ratio of macrophages to colon cancer cells inhibited cancer cell growth. This was partially dependent on cell-to-cell contact, whereas Boyden chamber cocultivation without cell-to-cell contact promoted cancer cell spread.Conclusions: In conclusion, our data indicate that a dense macrophage infiltration at the tumor front positively influences prognosis in colon cancer and that the degree of cell-to-cell contact may influence the balance between protumorigenic and antitumorigenic properties of macrophages.