Hepatic metastases of colorectal cancer are rather homogeneous but differ fromprimary lesions in terms of immune cell infiltration.

摘要

The immune system plays an important role in shaping the clinical course ofcolorectal cancer (CRC). However, it is still unclear how the immune infiltrates of primary CRC lesions and distant metastases by immune effector cells arerelated to each other. To address this issue, we quantified CD3(+), CD8(+) andgranzyme B(+) lymphocytes in primary CRC samples and corresponding livermetastases. This analysis showed that the prognostic predictions that can bedrawn from the infiltration of immune cells in primary CRCs and their metastases are heterogeneous. To investigate whether such heterogeneity would also beobserved within CRC hepatic metastases, the density of the immune infiltrate and cytokine production were assessed in opposite sides of the same metastaticlesion. In addition, tumor-infiltrating lymphocytes were assessed in sequentialsections 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, perhapsindicating a major impact for local causes on tumor infiltration by immune cells.In summary, our study demonstrates a consistent degree of heterogeneity betweenprimary tumors and hepatic metastases but an excellent intra-lesionalhomogeneity. These findings may be of key importance for patient stratificationand the development of personalized strategies against CRC.