Thomas Gajewski, professor of cancer immunotherapy and pathology and medicine at University of Chicago Medicine, won the 2019 European Society for Medical Oncology (ESMO) Award for Immuno-Oncology in recognition of his landmark work uncovering why some patients are resistant to immunotherapy and how to restore the immune system’s ability to fight cancer.
Gajewski, MD, PhD, joined UChicago Medicine more than two decades ago. He has been working on fundamental aspects of the way the immune system fights tumors and why some patients do not respond to immunotherapy, translating his discoveries into new treatment strategies.
He is particularly dedicated to the research and development of treatments for melanoma — a form of skin cancer — with a special interest in immunotherapies against the disease. He also leads the development of immune-based therapies for other cancers, using discoveries made in his lab to launch new clinical trials.
“Gajewski is a globally recognized leader in oncology research, and deserving of this recognition from ESMO,” Michelle M. Le Beau, PhD, professor of medicine and director of the UChicago Medicine Comprehensive Cancer Center, said in a press release. “His discoveries have shaped the field of cancer immunology and transformed the treatment landscape.”
One of Gajewski’s most important contributions was the characterization of the immune checkpoint CTLA-4, a protein found on T cells — a type of immune cell that can fight cancer cells — that keeps immune responses in check and prevents T-cells from killing cancer cells.
Immune checkpoint inhibitors work by blocking checkpoint proteins including CTLA-4, PD-1, and PD-L1. This “takes the brakes off” the immune system, increasing the ability of T-cells to kill malignant cells. Many immune checkpoint inhibitors have been approved as cancer therapies, and several others are in clinical testing.
Another of Gajewski’s breakthrough discoveries was finding that patients with a specific gene “signature” of activated genes pulling T-cells into the tumor area are more likely to respond to immunotherapies. These tumors filled with T-cells were dubbed “hot” or “T cell-inflamed tumor microenvironment.”
Distinguishing between T-cell-inflamed and non-T-cell-inflamed, or “cold” tumors that lack T-cells, could be a robust way of predicting which patients are likely to respond to current immunotherapies, as it could provide critical information to design treatment strategies that overcome treatment failure in unresponsive patients.
In 2014, Gajewski’s group found that a protein complex called simulator of interferon genes (STING) is a key sensor that alerts immune cells of the first line of defense to set an antitumor attack. The discovery led to the development of STING mimic molecules that are currently in clinical testing for cancer treatment.
In 2018, he and his colleagues published a study showing that the presence of certain strains of bacteria in the gut flora could improve the response to immunotherapy in people with advanced melanoma. The presence of these bacteria appears to increase the recruitment of T-cells into the tumor site, boosting response to immunotherapy.
This discovery set the stage for a patent application and a licensing agreement with Evelo Biosciences, leading to a Phase 1 clinical trial of the first microbial cancer therapy.
Three of Gajewski’s patent files are licensed to companies developing immunotherapies. In collaboration with UChicago’s Polsky Center for Entrepreneurship and Innovation, he founded his own company, Pyxis Oncology, whose mission is to develop immunotherapies based on the researcher’s discoveries.
“Many of us have been doing research in the field of cancer immunotherapy for over 20 years, and it is amazing to see the progress that is currently benefiting so many patients,” Gajewski said in an ESMO press release. “It is humbling to be recognized as perhaps representative of this group, and especially by my European colleagues.”
“Our view is that the clinical benefit of checkpoint blockade immunotherapy will hit a plateau, so understanding mechanisms of resistance or failure of the current approaches is necessary to expand efficacy further,” Gajewski said.