Cellular diversity helps liver cancer shrug off immunotherapy

2019

Challenge

The many cells that make up a tumor can display vast differences in behavior. Some evidence suggests that this variation can help tumors adapt to their environments and develop resistance to treatments. A better understanding of cellular variation within tumors could enable the development of new treatments for cancers that currently have a poor prognosis, such as liver cancer.

Advance

IRP researchers led by senior investigator Xin Wei Wang, Ph.D., discovered that, in patients with liver cancer, the extent of cellular diversity within a tumor may affect its response to a form of immunotherapy that blocks the tumor’s ability to prevent immune cells from attacking it. More specifically, the researchers’ analysis found patients whose tumors contained less variation among their cells responded better to experimental immunotherapies in clinical trials than patients with greater cellular diversity.

Impact

These findings suggest that examining a tumor’s cellular diversity can help clinicians predict how a cancer will respond to immunotherapy. Moreover, by understanding the impact of cellular diversity within liver tumors, researchers will be better positioned to devise treatments for patients whose cancers are unlikely to respond to immunotherapy alone, thus improving patient outcomes.

Publications

Ma L, Hernandez MO, Zhao Y, Mehta M, Tran B, Kelly M, Rae Z, Hernandez JM, Davis JL, Martin SP, Kleiner DE, Hewitt SM, Ylaya K, Wood BJ, Greten TF, Wang XW. (2019). Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. Cancer Cell. Oct 14;36(4):418-430.e6.