Checkpoint inhibitors, a type of immunotherapy, that target myeloid immune cells and slow tumor growth were discovered by a team from the Perelman School of Medicine and other institutions. Reporting in Nature Cancer, the researchers showed for the first time in human cells and a mouse model that inhibiting the c-Rel molecule in myeloid cells—as opposed to lymphoid cells that today’s immunotherapies target—blocked the production of immune suppressor cells and significantly shrank tumors.
Checkpoint inhibitors blocks proteins, called checkpoints, that are made by some types of immune system cells, such as T-cells. These checkpoints help keep immune responses from being too strong, but they often keep T-cells from killing cancer cells. These therapies have changed the cancer landscape by showing survival benefits where traditional therapies, like chemotherapy, may have failed. However, the number of patients who respond to these types of therapies remains limited, pushing researchers to explore a new class of inhibitors.
The findings not only show the potential of this new immunotherapy, but also point to a previously unknown pathway of cancer’s assault on the body involving what are known as myeloid-derived suppressor cells (MDSCs). Cunning tumor cells, the authors found, hijack c-Rel to produce MDSCs that keep the immune system from attacking the cancer. The Penn-developed inhibitor releases that break.
“c-Rel is generally considered to be a promotor of immune responses, not a suppressor. That’s why this discovery is surprising and unexpected,” says senior author Youhai H. Chen, a professor of pathology and laboratory medicine in the Perelman School of Medicine. “There are two big takeaways: Conceptually, this is a new pathway of cancer development that wasn’t known before. And we have shown that a new drug inhibitor targeting this pathway works as well, if not better, than the first generation of checkpoint blockers.”
Read more at Penn Medicine News.