New Discoveries and Honors in Cancer Research

Read the latest cancer research and recognition from the members of the Damon Runyon scientific circle.
June 4, 2021
New potential target for immunotherapy identified

One of the many ways tumor cells evade capture by the immune system is by presenting proteins on their surface that signal “don’t touch me” to immune T-cells. These proteins are called immune checkpoints. Therapies that block them—known as immune checkpoint blockades (ICB)—are remarkably effective, but they only work for a minority of cancer patients.

In search of more widely beneficial immunotherapies, Damon Runyon Physician-Scientist Gabriel Griffin, MD, and colleagues at the Broad Institute of MIT and Harvard are investigating other mechanisms of immune system evasion to target in combination with ICB. Specifically, they have set out to find epigenetic regulators—proteins that turn genes “on” and “off”—that play a role in helping cancer cells avoid detection.

To identify these faulty epigenetic regulators, the team used the gene editing tool CRISPR to selectively knock out 936 different regulators in mouse tumors treated with ICB. They found when they knocked out a regulator called SETDB1, the tumor cells became exposed to immune cell attack, indicating that SETDB1 is responsible for keeping those tumor cells hidden by turning “off” sections of the genome. Further, the researchers found that the SETDB1 gene is overexpressed in ICB-resistant human tumors, confirming its role in immune system evasion.

With these findings, Dr. Griffin’s team has established a new potential target for immunotherapy. A better understanding of exactly how SETDB1 functions within tumor cells to render them “invisible” to immune cells could lead to treatments that, combined with ICB, are effective for a wider range of patients than ICB alone.


Read more about this research in Nature.