MICs shed light on prostate cancer

The body's immune system has built in anti-tumor mechanisms. In order for cancers to form, one of the molecular steps that must occur is for the tumor cells to develop the means to avoid being attacked by this defense mechanism. There are several different methods by which the immune system can eradicate tumors early in their development. One tumor immune surveillance mechanism utilizes the fact that a specific molecule, the MHC class I chain–related molecule (MIC), is often expressed on the surface of some tumor cells. MICs interact with the immune system's natural killer cells and trigger them to destroy the tumor cells.

Jennifer Wu and colleagues, at the University of Washington, now investigate how prostate cancers evade this anti-tumor defense strategy. The researchers found that MIC-expressing prostate cancer cell lines were able to activate natural killer cells, thus, initially, this defense mechanism appeared intact. Analysis of prostate tumor biopsies showed that the cell surface localization of MIC was highest in early-stage tumors. The researchers noted that tumors from later-stage patients, however, could no longer activate natural killer cells, and that there were high levels soluble MIC in the blood serum of these patients.

These data showed that the later stage tumors were shedding the MIC from their cell surfaces, and that this was the means by which prostate cancer cells could overcome this particular form of immune surveillance. The deficiency in the ability to activate natural killer cells could be overcome in tissue culture by stimulating the cells with the cytokine IL-2 or IL-15. The authors further investigated how soluble MIC level in serum related to prostate-specific antigen (PSA); PSA measurements are used as a biomarker for the presence of prostate cancer. Soluble MIC serum levels did not correspond with PSA serum levels, but they were highly correlative with high-grade and invasive tumor status in prostate cancer patients.

This work indicates that development of the means to evade the MIC activated immune surveillance system may be a mechanism for prostate cancer progression, that soluble MIC measurement may be a useful biomarker for disease progression, and that cytokine treatment may aid in reestablishing natural killer cell anti-tumor activity.

TITLE: Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer

AUTHOR CONTACT:
Jennifer D. Wu University of Washington, 325 9th Ave., Seattle, WA 98104, USA Phone: 206-341-5349; Fax: 206-341-5302. E-mail: wuj@u.washington.edu

View the PDF of this article at: http://www.jci.org/cgi/content/full/114/4/560

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