Researchers unlock key secrets showing how tumors hide from immune system

In one of the biggest advances to come from the H. Lee Moffitt Cancer Center & Research Institute in its 16-year history, researchers have unlocked at least part of the mystery of how tumors flourish undetected by keeping their presence a secret from sentries of the body’s immune system.

“Flying beneath the radar” is how Nature Reviews Cancer (http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrc/journal/v4/n1/full/nrc1261_fs.html) labels the mechanism of tumors evading capture, a process described by Hua Yu, Ph.D., and her colleagues at Moffitt and the University of South Florida College of Medicine. Their findings are published in the current issue of the journal Nature Medicine.

“Cancer is allowed to wreak havoc on the body’s immune system because it knows how to fool the body’s defensive arsenal,” explains Jack Pledger, Ph.D., Associate Center Director for Basic Science and Professor of Biochemistry at USF. “The discoveries of Dr. Yu give us vital information about how tumors stay ’invisible.’ It opens the way for new treatments to help flush the cancer cells into the open, so the body’s armies against disease can destroy them.”

Yu is an Associate Professor in the USF Department of Medical Microbiology and Immunology and the Immunology Program at Moffitt. Her coauthors on the study include Drew Pardoll, M.D., Ph.D., from the Johns Hopkins University School of Medicine, together with Richard Jove, Ph.D., and William Dalton, Ph.D., M.D., both from Moffitt and USF. Other authors include Tianhong Wang, Ph.D.., Guilian Niu, Ph.D., Lyudmila Burdelya, Ph.D., and Marcin Kortylewski, Ph.D. The study is titled “Regulation of the innate and adaptive immune responses by Stat3 signaling in tumor cells.”

The researchers documented that the tumor’s activation of Stat3 (from the STAT family of proteins that regulates genes) secretes factors that inhibit the body’s immune responses by keeping dendritic cells from maturing. The activation also blocks expression of inflammatory mediators required to trigger the immune system.

Other ongoing research at Moffitt related to Stat3 includes using microarray technology to study the characteristic gene expression profiles or “molecular signatures” of certain genes that are regulated by the STAT. Scientists suspect that many genes that are directly or indirectly regulated by Stat3 may contribute to cancer, and they are working to develop new drugs based on inhibiting Stat3 for more effective treatment of breast cancer, prostate cancer, sarcoma, melanoma and other tumors that harbor aberrantly activated Stat3.