Discovery opens door to new strategy for cancer immunotherapy

New research by Dana-Farber Cancer Institute scientists raises the prospect of cancer therapy that works by converting a tumor’s best friends in the immune system into its gravest enemies.

In a study published in the journal Science, an international collaboration of investigators from Dana-Farber, Harvard Medical School, Boston Children’s Hospital, and the University of Strasbourg uncovered a mechanism that allows key immune system cells to keep a steady rein on their more belligerent brother cells, thereby protecting normal, healthy tissue from assault. The discovery has powerful implications for cancer, immunotherapy researchers say: by blocking the mechanism with a drug, it may be possible to turn the attack-suppressing cells into tumor-attacking cells.

“Our findings suggest a new strategy for immune system-based therapies for cancer,” said the study’s senior author, Harvey Cantor, MD, of Dana-Farber and Harvard. “By targeting a genetic pathway in cells that ordinarily restrain the immune response to cancer, we may be able to convert them into cancer fighters. The challenge now is to develop antibodies and small-molecule drugs that can trigger that change.”

The study grew out of a desire to understand the biology behind a basic part of the immune response. In reaction to infection or inflammation, immune system cells known as effector T cells (T_effs) undergo rapid changes – arming themselves and diversifying into groups that target specific diseased cells. A second type of immune system cell, called regulatory T cells (T_regs), are a model of constancy, remaining stable even as T_effs go into battle mode. Such persistence is critical, as T_regs’ role is to keep T_effs under control and prevent them from damaging normal tissue.

Cantor and his associates set out to discover how T_regs maintain their stoic stability. They noted that T_regs generally had high levels of a protein called Helios, a transcription factor that helps switch genes on and off. They then discovered that T_regs with low levels of Helios were rather unstable – too unsteady to keep the immune response in check.