Journal club: Peritumoral neutrophils link inflammatory response to disease progression by fostering angiogenesis in hepatocellular carcinoma

This journal article (J. Hepatol, May 2011)  focused on the histologic microenvironment that surrounds hepatocellular carcinoma.  In particular, we discussed the interaction between IL-17 producing lymphocytes and peritumoral neutrophils.  The Chinese authors of this study (see link below) were able to determine that IL-17 producing lymphocytes recruit CD15+ neutrophils to the tumor periphery; these cells were far more abundant at the periphery (compared to outside the tumor and within the tumor).  A higher density of neutrophils at the tumor periphery was associated with lower overall survival as well as lower tumor-free survival.

The recruitment occurs via the upregulation of many CXC chemokines, which were also found to be in higher quantity at the tumor periphery.  These tumor-specific neutrophils were found to secrete MMP9 (an enzyme that is associated with tumor invasion and metastasis, via promotion of angiogenesis).  MMP9 colocalized with neutrophils- shown on a beautiful confocal microscopy image.  By blocking MMP9, less angiogenesis occured (inhibits capillary tubule formation).  In addition, levels of VEGF were increased at the tumor periphery.

In conclusion, the specific nature of inflammation may determine the ability of the inflammatory reponse to facilitate or prevent tumor growth; modulationg the functional activity of neutrophils might provide a novel strategy for anticancer therapy.

For the full article, click below:

microenvironment

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