Immunotherapy as a field for cancer treatment has been rapidly developing in the United States. The therapies that incite the immune system’s natural power to fight disease have benefited many patients, even allowing for complete remission in some. Unfortunately, immunotherapy’s power is not successful in all cases, and one of the biggest research questions remains how to increase its efficacy in more cancers and in more patients. A team from Harvard Medical School recently developed a tool that could help scientists to better understand immunotherapy treatments.
The research teams are based at the Blavatnik Institute of Massachusetts General Hospital, Beth Israel Deaconess Medical Center, and Brigham and Women’s Hospital. They created a single-cell sequencing map to better visualize the landscape of myeloid tumor cells from patients with lung cancer.
Past immunotherapy research has largely focused on T-cells, or immune cells that learn to recognize specific proteins and then attack. But tumors are made up of a mixture of many different kinds of cells, including those known as tumor-infiltrating myeloid cells. These cells could be alternative targets in immunotherapy treatments, but the role they play is still not fully understood.
The study was published in Immunity, and it showed that 25 myeloid cell subpopulations that were lately previously unknown, had unique gene expression signatures that were uniform across all of the patients. A majority of these subpopulations were also found in a mouse model of lung cancer, which suggests that there is a large amount of similarity in myeloid cells, even across species.
These preliminary results will open up avenues for more research that will help to account for the specific roles of myeloid cells in cancer and to determine if they may be targets for new or improved immunotherapies. Co-corresponding study author Allon Klein, assistant professor of systems biology at HMS, said that part of the reason many cancer patients don’t respond to immunotherapy “could certainly lie at the level of myeloid cells, which interact heavily with both tumor cells and T-cells. By identifying the rich complexity of myeloid cell states in tumors, we now have a powerful starting point to better understand their functions and clinical applications.”
One of the most important findings of this study is that myeloid subpopulations can be found in different human patients and in mice, which means that mouse models could be useful in future research.
The study not only created immediate research opportunities, it also helps to shed light on other work initiatives like the Human Tumor Atlas, which is aiming to map the landscape of all cell types in the human body.
“This work fits into a single-cell revolution that’s happening in many areas of biomedicine, particularly in immunology,” Klein said. “To improve immunotherapies, we need to know as much as we can about the cells and processes involved. This requires a true team effort, and our study couldn’t have been possible without fantastic collaborations across the medical school.“