After decades of research, a myriad of new treatments, tailored or quasi-tailored to specific tumors, are becoming common practice among physicians. But the treatments come with a caveat -- for some patients, after an initial positive response to treatments such as immunotherapy, the initial remission is followed some time later by a reappearance of the tumors, and, this time, the tumors plan on staying. When the cancer recurs, it has acquired a subpopulation of cells "immune" to the initially effective treatment. Jennifer Landsberg, of the Laboratory of Experimental Dermatology at the University of Bonn, and her collaborators genetically engineered a mouse melanoma model to explore why melanoma becomes resistant to immune therapy. They reported their findings in the October 11, 2012 issue of Nature
Immunotherapy treatments shrink the tumor by means of the patient's own weapons arsenal. The administered antibodies "snitch" on the cancer cells, making them visible to the immune system. Once the tumor cells are no longer able to grow undercover, immune cells kill them, reducing the tumor in a short time. But when the melanoma returns after a patient has undergone immunotherapy, the immune system seems no longer able to target and kill the cancer cells.
Contrary to what was widely accepted, Landsberg and colleagues found that the reason melanoma becomes resistant to immune therapy is not genetic variability -- it's not that different cells in the tumor accumulate mutations so that some cells will be effectively targeted and others won't. Rather, the resistance comes from dedifferentiation of some tumor cells. A number of cells react to the immune attack by reprogramming or changing their antigen expression in such a fashion that they become, again, undetectable by the immune system.
These observations from the mouse model mean that researchers now have an idea of "what to look for in these cases," said Dr. Antoni Ribas -- author of the accompanying News and Views article
. If a similar mechanism enabling recurring melanomas to resist immune attack is observed in humans, new avenues for melanoma treatment may open.
*If you want to know more about melanoma, and you speak Spanish, check out this week's podcast
in which we interview Antoni Ribas at the Department of Medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles.