Gal1 induces apoptosis in T helper 1 cells, which fight tumors.
Dana-Farber Cancer Institute scientists identified a protein that prevents the body’s immune system from recognizing and attacking Hodgkin lymphoma cells.
The biological trademark of Hodgkin lymphoma is a type of giant, mutant white blood cell called the Reed-Sternberg cell that is found in the lymph node tumors. Hodgkin tumors contain only about 5% cancerous Reed-Sternberg cells. The rest are different types of immune cells recruited to fight the tumor but they are ineffective, report the researchers.
The Hodgkin tumors are overloaded with T helper 2 (Th2) cells, which normally control allergic responses, and T regulatory (Treg) cells, which suppress other T-cell types and shut down an immune response when the job is done. These cells act as bodyguards for the cancer by weakening the T helper 1 (Th1), designed to recognize and kill foreign infectious agents and sometimes tumors.
Using gene microarray chips, the investigators looked for genes that were active in Reed-Sternberg cells but not in cells of another non-Hodgkin B-cell lymphoma. The comparison revealed that a gene called Gal1 was up to 30 times more active in the Reed-Sternberg cells, causing them to secrete large quantities of a protein, Gal1 or Galectin 1, that turns down the Th1 immune response.
The team then defined the mechanism for Gal1 overexpression in Hodgkin lymphoma. Next, they demonstrated that Th1 immune cells underwent apoptosis when treated with Gal1, leaving increased numbers of Th2 and Treg cells. Using RNAi, they then turned off the Gal1 gene in Hodgkin Reed-Sternberg cells and showed that it blocked the death of infiltrating normal Th1 cells, making them an equal force to the Th2 cells.
The researchers also believe that this strategy may not be limited to Hodgkin lymphoma. One of the collaborating authors on the study at the University of Buenos Aires has blocked Gal1 in mice with melanoma, and the animal’s immune system succeeded in eliminating the cancer, they reported.
The study is posted online by the Proceedings of the National Academy of Sciences on July 30 and will appear in an upcoming print issue of the journal.
