Early Events of Hepatic Metastasis Formation in Mice: Role of Kupffer and NK-Cells in Natural and Interferon-γ-Stimulated Defense

Rushfeldt, Christian; Sveinbjørnsson, Baldur; Seljelid, Rolf; Smedsrød, Bård

doi:10.1006/jsre.1998.5532

Cited by 62 publications

(42 citation statements)

References 42 publications

(53 reference statements)

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“…35,36 Current research attributes a predominantly anti-tumor phenotype to KCs during the early stages of tumor establishment. [37][38][39] Our study in agreement with these reports indicates early KC depletion to have a tumor stimulatory effect. The anti-tumor activity of KCs at this early stage is attributed to their phagocytic properties, 40 while captopril exerts its anti-tumor effect through inhibition of angiogenesis, tumor proliferation and reduction in inflammation.…”

Section: Discussionsupporting

confidence: 92%

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

Wen

Ager

Neo

et al. 2013

Cancer Biology & Therapy

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Section: Discussionsupporting

confidence: 92%

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

Wen

Ager

Neo

et al. 2013

Cancer Biology & Therapy

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“…In addition, NK cells are abundantly present in the systemic circulation and in the liver, the first organ of tumor cell dissemination in most patients with colorectal cancer. 36 . Especially, patients with MSI þ tumors may benefit from immunotherapy and patients with HNPCC may be able to receive preventive vaccinations, for instance, as described above that stimulate NK and T cells.…”

Section: Discussionmentioning

confidence: 99%

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

Menon

Rhijn

Morreau

et al. 2004

Laboratory Investigation

199

172

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The efficacy of tumor cell-immune cell interactions depends on a number of factors, for example, the expression of HLA-I on tumor cells, the type of immune cell, the accessibility of tumor cells for immune cells and the expression of immunogenic epitopes. We assessed infiltration of CD4 þ , CD8 þ , CD56 þ and CD57 þ cells in the tumor epithelium, tumor stroma and advancing tumor margin of 93 colorectal carcinomas and correlated this to clinicopathological parameters, the expression of HLA-A and HLA-B/C on tumor cells, the presence of a basal membrane (BM)-like structure surrounding tumor nodules and the presence of microsatellite instability/ mutator phenotype (absent MLH-1 expression). The median intraepithelial CD4 þ , CD8 þ , CD56 þ and CD57 þ cell infiltrations were 3, 23, 0 and 0 cells/mm 2 tumor, respectively. HLA-A/BC expression by tumor cells was normal in 28/43%, heterogeneous in 59/48% and absent in 13/9% of the cases. A BM-like structure surrounding the tumor nodules was absent, present and thick in 47, 38 and 15% of the cases. Six cases lost MLH1 expression. There was a positive correlation between leukocyte infiltration in the three compartments for CD4 þ , CD8 þ , CD56 þ (partly) and CD57 þ (all Po0.05) cell infiltration. Intraepithelial CD8 þ cell infiltration inversely correlated with HLA-A (P ¼ 0.04) and HLA-B/C expression (P ¼ 0.04). Intraepithelial CD57 þ cell infiltration inversely correlated with HLA-B/C expression (P ¼ 0.04). Moreover, intraepithelial infiltration of CD8 þ and CD57 þ cells was inversely correlated to the presence of a BM-like structure (P ¼ 0.003 and 0.04, respectively). Uni-and multivariate analyses showed that a lower tumor stage (P ¼ 0.004) and marked infiltration of CD8 þ (P ¼ 0.04) and CD57 þ cells (P ¼ 0.05) at the advancing tumor margin were independent prognostic factors for a longer diseasefree survival. Loss of MLH1 expression was correlated with a significantly higher intraepithelial CD8 þ and CD57 þ cell infiltration. We conclude that infiltration of CD8 þ and CD57 þ cells are important prognostic factors in colorectal cancer. However, their interaction with tumor cells is inversely correlated to the presence of HLA-I on tumor cells and a thick BM-like structure around tumor islets. Our data indicate that NK cells might play an important role in the immune surveillance in colorectal cancer patients.

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“…NK and KC are mobile cells and can be seen moving along the hepatic sinusoid in in vivo microscopy experiments (our unpublished data). At this stage, the NK and KC are seen to be associated with the majority of the tumour cells, resulting in cytolysis and subsequent phagocytosis of the majority of the cancer cells [7][8][9] . Subsequently, specific adhesion of tumour cells within the hepatic microcirculation and active extravasation of the surviving cancer cells through the damaged hepatic endothelium takes place [10] .…”

Section: Colorectal Cancer and The Hepatic Sinusoidal Immune Systemmentioning

confidence: 99%

The hepatic sinusoidal endothelial lining and colorectal liver metastases

Braet¹,

Nagatsuma²,

Saito³

et al. 2007

WJG

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Colorectal cancer (CRC) is a common malignant disease and the severe nature of cases in men and women who develop colorectal cancer makes this an important socio-economic health issue. Major challenges such as understanding and modeling colorectal cancer pathways rely on our understanding of simple models such as outlined in this paper. We discuss that the development of novel standardized approaches of multidimensional (correlative) biomolecular microscopy methods facilitates the collection of (sub) cellular tissue information in the early onset of colorectal liver metastasis and that this approach will be crucial in designing new effective strategies for CRC treatment. The application of X-ray micro-computed tomography and its potential in correlative imaging of the liver vasculature will be discussed.

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Early Events of Hepatic Metastasis Formation in Mice: Role of Kupffer and NK-Cells in Natural and Interferon-γ-Stimulated Defense

Cited by 62 publications

References 42 publications

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

The renin angiotensin system regulates Kupffer cells in colorectal liver metastases

Immune system and prognosis in colorectal cancer: a detailed immunohistochemical analysis

The hepatic sinusoidal endothelial lining and colorectal liver metastases

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