by Elise Wachspress
In the world of cancer research, Thomas Gajewski, MD, PhD, is a rock star. And not just because he plays lead guitar for The Checkpoints, an all-cancer-researcher band that includes his longtime colleague Jim Allison, last year’s Nobel Prize winner for physiology or medicine (and professor at the MD Anderson Cancer Center) on harmonica.
Named a Giant of Cancer Care in 2017, Gajewski has, for more than two decades, worked in cancer immunotherapy, a field only recently recognized as the most promising for actual cancer cures—a word that makes most clinicians nervously back away.
Gajewski has dedicated his career to figuring out how to help patients’ immune systems fight cancer from within. Much of his work has focused on checkpoint inhibitors, proteins which our bodies use to keep immune responses in check, so we don’t attack beneficial bacteria or our own cells. But checkpoint inhibitors can also keep our immune system from killing cancer cells (and thus the name chosen for Gajewski’s band).
Over the past century, the idea of fighting cancers with immunotherapies has fallen in and out of favor multiple times. But oncologists are now watching the field—and Gajewski’s work—with excitement. Recent research shows that, in metastatic melanoma and many other solid cancers, immunotherapies cause tumors to regress or even disappear in 30-50% of patients. These treatments are often significantly less toxic than surgery, radiation, or traditional chemotherapy. And by training the body to recognize and kill cancer cells, immunotherapies offer an opportunity for truly durable results, offering patients a chance at living long, healthy, cancer-free lives.
But Gajewski, the AbbVie Foundation Professor of Cancer Immunotherapy, is focused past these success stories. What drives his curiosity and his passion is understanding why immunotherapies fail. And one of his most remarkable findings is that the bacteria patients carry in their guts—their microbiome—can strongly influence whether or not cancer immunotherapy works.
As with most scientific breakthroughs, this one came through a combination of dogged dedication, careful observation, and wonder. When Gajewski and his team implanted mice with melanoma tumors, they noticed immunotherapy response differed depending upon the commercial source of the animals themselves; one supplier’s mice fared much better, even though they were identical strains. The team finally found that the mice were delivered to the lab carrying a certain type of gut bacteria responded much better to the therapy.
Even more tantalizing: when the two sets of mice were housed together, outcomes improved for the mice from the other supplier. Sharing these healthy gut bacteria was key to therapeutic success.
Gajewski and team are now working to identify bacteria found in humans that can produce these effects in mice. The team will use a system in which germ-free mice are colonized with microbial material from patients, implanted with tumors, and then treated with immunotherapy drugs. The goal is to figure out the exact mechanism of how bacteria promote or restrict anti-tumor immunity—knowledge that will provide a foundation for new therapeutics. By developing computational algorithms which integrate genomic sequencing of the microbiota, the tumor oncogenes, and germline polymorphisms, they aim to get a comprehensive view of immunotherapy success versus resistance in each individual patient.
The goal is a diagnostic approach that will help clinicians—like Gajewski himself—decide the most effective way to use immunotherapy for each patient and tumor, perhaps by simply introducing new types of bacteria to a patient’s gut. While we commonly think of probiotics as a way to improve digestion or alleviate allergies, we may one day find an avenue to use much more sophisticated, designer probiotics to treat some cancers.
Gajewski recently received a promise of nearly half a million dollars from the Melanoma Research Alliance to advance this research. However, securing this award requires him to match the grant with similar funding from other sources.
For anyone ready to invest in much more effective, less debilitating treatments—perhaps even cures—for cancer, Gajewski has a strategy ready for prime time, a track record of unusual research success, and a group of musicians ready to sing about it.
Elise Wachspress is a senior communications strategist for the University of Chicago Medicine & Biological Sciences Development office