Immune system fights stem cells’ dark side

If proteins were celebrities, OCT4 would be on the A-list. In 2007, in a dramatic advance, several researchers showed that inserting the gene for OCT4 and just a few other genes transformed adult skin cells into stem cells capable of generating any tissue in the body.

But in addition to the vast healing potential of stem cells, some fear that using them for therapy may cause tumors, and others believe that tumors regrow in cancer patients when a tiny number of stem cells in tumors survives therapy and continues regenerating.

OCT4 is commonly expressed in germ-cell tumors (GCTs) such as testicular cancer and some ovarian cancers. In the April 17 online edition of Proceedings of the National Academy of Sciences, a team led by Madhav V. Dhodapkar, M.D., the Arthur H. and Isabel Bunker Professor of Hematology, found that the immune system commonly targets this protein and that this immune response correlates with the development of GCTs. Only 35 percent of newly diagnosed GCT patients had an immune response to OCT4, compared to more than 80 percent of healthy humans. Interestingly, after chemotherapy, an anti-OCT4 immune response was seen in 83 percent of the GCT patients.

The work could lead to trials of immune therapies for cancer that target pathways involving stem cells.