The anti-diabetic drug phenformin may have structural and therapeutic advantages over its sister compound metformin for future cancer treatment.
- In mice treated with cancer immunotherapy, shining a cosmetic laser on a tumor boosted the therapy’s effectiveness.
- The strategy stimulated the immune system to attack nonmutated proteins on the tumor.
- The findings may help investigators make cancer immunotherapy effective against currently incurable cancers.
David E. Fisher, MD, PhD
We discovered that use of a cosmetic laser, when shined on a tumor, could strongly enhance immune attacks against nonmutated tumor proteins.
Director, Mass General Cancer Center Melanoma Program
BOSTON – Use of a cosmetic laser invented at Massachusetts General Hospital (MGH) may improve the effectiveness of certain anti-tumor therapies and extend their use to more diverse forms of cancer. The strategy was tested and validated in mice, as described in a study published in Science Translational Medicine.
Immune checkpoint inhibitors are important medications that boost the immune system’s response against various cancers, but only certain patients seem to benefit from the drugs. The cancer cells of these patients often have multiple mutations that can be recognized as foreign by the immune system, thereby inducing an inflammatory response.
In an attempt to expand the benefits of immune checkpoint inhibitors for additional patients, a team led by David E. Fisher, MD, PhD, director of the Mass General Cancer Center’s Melanoma Program and director of MGH’s Cutaneous Biology Research Center, conducted experiments in mice with a poorly immunogenic melanoma that is not hindered by immune checkpoint inhibitors. The researchers found that exposing the melanoma cells to ultraviolet radiation caused them to take on more mutations, which made immune checkpoint inhibitors more effective at boosting the immune response against the melanomas. Somewhat unexpectedly, the enhanced response included immune attack against non-mutated proteins in the tumor, a process called “epitope spreading.”
“Epitope spreading could be important because many human cancers do not have very high mutation numbers, and correspondingly do not respond well to immunotherapy, so a treatment that can safely target nonmutated proteins could be valuable,” Fisher explains.
The researchers next sought to find a substitute for the response triggered by mutations after ultraviolet radiation, since it’s likely not safe to add mutations to a patient’s tumor as a treatment strategy. “We discovered that use of a cosmetic laser, also known as a fractional laser, developed at MGH, when shined on a tumor, could trigger a form of local inflammation that mimicked the presence of mutations, strongly enhancing immune attacks against nonmutated tumor proteins, thereby curing many mice of tumors that otherwise did not respond to immunotherapy,” says Fisher.
The findings suggest that using such a laser approach, or other methods to optimize immune responses against nonmutated targets on tumors, might make immune checkpoint inhibitors effective against currently incurable cancers.
This work was supported by the National Institutes of Health; the National Science Foundation; the Cancer Research Institute; the Leukemia and Lymphoma Society; the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Evergrande Center for Immunologic Diseases; Cancer Research UK; the Mildred Scheel Grant of the German Cancer Society; the Filling the Gap Grant of the University of Zurich, Switzerland; and the Swiss National Science Foundation.
About the Massachusetts General Hospital
Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In August 2020, Mass General was named #6 in the U.S. News & World Report list of "America’s Best Hospitals."