Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration.
Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration.
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DOI：
10.4161/onci.24116
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发表时间：
2013-04-01
期刊：
影响因子：
7.2
通讯作者：
Zoernig I
中科院分区：
文献类型：
--
作者：
Halama N;Spille A;Lerchl T;Brand K;Herpel E;Welte S;Keim S;Lahrmann B;Klupp F;Kahlert C;Weitz J;Grabe N;Jaeger D;Zoernig I
免疫系统在形成结直肠癌（CRC）的临床过程中起着重要作用。然而，目前还不清楚免疫效应细胞对原发性CRC病变和远处转移灶的免疫浸润是如何相互关联的。为了解决这个问题，我们定量了原发性CRC样本和相应肝转移灶中的CD 3+、CD 8+和颗粒酶B+淋巴细胞。该分析表明，可以从原发性CRC及其转移瘤中的免疫细胞浸润中得出的预后预测是异质性的。为了研究在CRC肝转移瘤中是否也会观察到这种异质性，在相同转移性病变的相对侧中评估免疫浸润和细胞因子产生的密度。此外，在同一转移病灶的连续切片中评估肿瘤浸润淋巴细胞，间距为30 μm。总之，在同一病变内检测到一致的细胞计数和细胞因子水平。然而，对一例同步转移的研究表明，同一患者的不同转移病灶可能是异质性的，这可能表明局部原因对免疫细胞的肿瘤浸润有重大影响。总之，我们的研究表明原发性肿瘤和肝转移瘤之间的异质性程度一致，但病灶内的同质性极好。这些发现可能对患者分层和针对CRC的个性化策略的发展至关重要。
The immune system plays an important role in shaping the clinical course of colorectal cancer (CRC). However, it is still unclear how the immune infiltrates of primary CRC lesions and distant metastases by immune effector cells are related to each other. To address this issue, we quantified CD3+, CD8+ and granzyme B+ lymphocytes in primary CRC samples and corresponding liver metastases. This analysis showed that the prognostic predictions that can be drawn from the infiltration of immune cells in primary CRCs and their metastases are heterogeneous. To investigate whether such heterogeneity would also be observed within CRC hepatic metastases, the density of the immune infiltrate and cytokine production were assessed in opposite sides of the same metastatic lesion. In addition, tumor-infiltrating lymphocytes were assessed in sequential sections of the same metastatic lesion, with a spacing of 30 μm. In summary, consistent cell counts and cytokine levels were detected within the same lesion. The study of a case of synchronous metastases, however, suggested that different metastatic lesions within the same patient may be heterogeneous, perhaps indicating a major impact for local causes on tumor infiltration by immune cells. In summary, our study demonstrates a consistent degree of heterogeneity between primary tumors and hepatic metastases but an excellent intra-lesional homogeneity. These findings may be of key importance for patient stratification and the development of personalized strategies against CRC.
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