Biological pathways provide evidence for how to overcome barriers limiting cancer immunotherapies

Researchers at UNC Lineberger Comprehensive Cancer Center have found a possible way to overcome barriers that block effective anti-cancer immune responses, thereby opening the potential for more effective immunotherapies in people.

The findings are published in Nature.

An unfavorable immune environment immediately surrounding a tumor cell is a major obstacle in using immunotherapy to treat many solid tumors, especially pancreatic and breast cancer, as the suppressive environment can block immune responses that could be helpful in attacking a tumor. One protein, the STimulator of INterferon Genes (STING), has the promise of powerfully provoking multiple parts of the immune system and breaking established barriers.

“Although activating the immune system to control malignant tumors has revolutionized cancer treatment, a sizable portion of patients do not respond to immunotherapy treatments. However, new drugs that target STING have been a high priority for pharmaceutical development yet clinical trials have revealed significant tumor resistance to STING-directed drugs,” said UNC Lineberger’s Jenny PY Ting, PhD, the William R. Kenan Professor of Genetics and professor of microbiology and immunology at the UNC School of Medicine.

“Clinically, to improve the effectiveness of STING-targeted drugs, we need to more deeply understand how these drugs influence different immune cells in the tumor because the beneficial effects of STING on immunity may be outweighed by its unintended immune-suppressive effect,” said Ting, the paper’s co-corresponding author and director of the Center for Translational Immunology at UNC.

The investigators primarily focused on pre-clinical models of pancreatic cancer as the disease has a five-year survival rate of only 10% in people and there are few treatment options. They also expanded the study to other solid tumors, including melanoma, triple-negative breast cancer and lung cancer. Importantly, what they observed in pancreatic cancer is broadly applicable to these additional cancers.

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