In findings that may help improve existing and experimental treatment strategies for metastatic melanoma, researchers have discovered how a subset of virulent stem cells may manipulate a person’s immune system into protecting the cancer instead of fighting it.
“The study provides evidence that cancer stem cells escape and downregulate host antitumor immunity,” said coauthor Markus Frank, an HMS assistant professor of pediatrics and a physician at the Transplantation Research Center of Children’s Hospital Boston and Brigham and Women’s Hospital.
The results extend the specialized activities attributed to cancer stem cells, the rare hardy cancer cells that renew themselves, give rise to the bulk of tumor cells, evade therapies and promote recurrence of cancer. Eliminating them is the ultimate goal of cancer stem cell research.
In studies of human melanoma samples, the researchers discovered sophisticated molecular mechanisms that the melanoma stem cells employ to selectively evade the initial immune assault. Perched on the surface of these stem cells are two co-stimulatory molecules, PD-1 and B7-2. These molecules appear to help the stem cells inhibit activation of immune system T cells, which can attack tumor cells in the body; induce regulatory T cells, which also inhibit T cells; and stimulate the inhibitory cytokine IL-10 via regulatory T cells.
The same research team first identified the malignant melanoma–initiating cells and their cancer stem cell properties (see Focus, Jan. 25, 2008) in a study led by pharmacologist and postdoctoral fellow Tobias Schatton.
The researchers hope to explore the implications of their work in cancer treatment by partnering on immunotherapeutic melanoma clinical trials conducted by coauthor Stephen Hodi or his colleagues at the Dana-Farber/Harvard Cancer Center.
The current paper, in the Jan. 15 issue of Cancer Research, is the latest in an ongoing collaboration between the Frank laboratory and the BWH Program in Dermatopathology, directed by George Murphy, HMS professor of pathology and chief of Dermatopathology at BWH.
For more information, students may contact Markus Frank at markus.frank@childrens.harvard.edu or George Murphy at gmurphy@rics.bwh.harvard.edu.
