title: Hepatic metastases of colorectal cancer are rather homogeneous but differ from primary lesions in terms of immune cell infiltration.
abstract: 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.
authors.affiliation: National Center for Tumor Diseases; Medical Oncology and Internal Medicine VI; University Hospital Heidelberg; Heidelberg, Germany ; Tissue Imaging and Analysis Center (TIGA); BIOQUANT; Heidelberg, Germany.
authors.forename: Niels
authors.initials: N
authors.lastname: Halama
authors.forename: Anna
authors.initials: A
authors.lastname: Spille
authors.forename: Tina
authors.initials: T
authors.lastname: Lerchl
authors.forename: Karsten
authors.initials: K
authors.lastname: Brand
authors.forename: Esther
authors.initials: E
authors.lastname: Herpel
authors.forename: Stefan
authors.initials: S
authors.lastname: Welte
authors.forename: Sophia
authors.initials: S
authors.lastname: Keim
authors.forename: Bernd
authors.initials: B
authors.lastname: Lahrmann
authors.forename: Fee
authors.initials: F
authors.lastname: Klupp
authors.forename: Christoph
authors.initials: C
authors.lastname: Kahlert
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Niels
authors.initials: N
authors.lastname: Grabe
authors.forename: Dirk
authors.initials: D
authors.lastname: Jaeger
authors.forename: Inka
authors.initials: I
authors.lastname: Zoernig
keywords: chemokines; colorectal cancer; cytokines; immune cells; liver metastases; lymphocytes