Nearly half of the 700,000 cancer patients who undergo surgical removal of a primary tumor each year suffer a recurrence of their disease at some point, and many of those patients will eventually die from their disease. The traditional view of recurrent tumors is that they are resistant to therapy because they've acquired additional genetic mutations that make them more aggressive and impervious to drugs. Now, however, researchers at the Perelman School of Medicine at the University of Pennsylvania show in an animal model that the enhanced aggressiveness of recurrent tumors may be due to changes in the body's immune response. The findings are published this week in the Proceedings of the National Academy of Sciences.
"Typically when a patient has a tumor recurrence, their oncologist treats them, much like they treated them for the primary tumor - with drugs aimed at the tumor cells themselves. But we've found that it might be better to attack the tumor cells and knock down the bad immune cells that are protecting the tumor," says senior study author Sunil Singhal, MD, assistant professor of Surgery and director, Thoracic Surgery Research Laboratory at the Perelman School of Medicine.
To assess the impact of anti-cancer vaccines on primary and recurrent tumors, the researchers immunized mice that had a primary or a recurrent tumor in their flank. Although both groups of animals developed an immune response to the vaccine, only the primary-tumor animals showed tumor shrinkage in response to the vaccine. The recurrent tumors appeared unaffected by the vaccine response. Moreover, this pattern held for several different vaccines.
Despite the prevailing models of tumor recurrence - which emphasize genetic changes in the tumor cells themselves - Singhal and colleagues could not find substantial genetic or behavior differences in the recurrent versus primary tumors that might account for the pattern of response.