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Research at Huntsman Cancer Institute (HCI) at the University of Utah (U of U) yielded new insights into the environment surrounding different types of lung tumors, and described how these complex cell ecosystems may in turn ultimately affect response to treatment. The results were published today in Immunity and featured on the print cover of the journal.
Lung cancer is the leading cause of cancer death among men and women. According to the American Cancer Society, the disease kills more people each year than colon, breast, and prostate cancers combined. Therefore, uncovering the precursors and behaviors of lung cancer remains a major target among scientists working to improve cancer outcomes.
Cells live in complex, distinct communities that scientists refer to as microenvironments. These microenvironments have many features that impact how a cell grows, how it behaves, and how it communicates with other nearby cells. In the case of cancer, researchers work to understand the microenvironment of a tumor to try to identify opportunities for possible therapeutic approaches.
“We sought to figure out why the immune microenvironment of lung cancer types were different,” says Trudy Oliver, PhD, HCI cancer researcher and associate professor of oncological sciences at the U of U, who oversaw the study. “We know that different kinds of tumor cells interact with different kinds of immune cells, and these immune cells have functions that can help or hurt the tumor. Essentially, tumors get these immune cells to do their dirty work for them,” says Oliver. “We noticed in both mice and in people that some tumors clinically thought of under the same umbrella are distinct in many ways that were not previously understood. Most strikingly, different lung tumor types were recruiting different types of immune cells.”
Using a mouse model developed by her lab, along with sophisticated single-cell sequencing technology, Oliver’s work uncovered clues to the role neutrophils, a type of immune cell, play in different types of lung cancer. In humans and other organisms, neutrophils are the body’s ‘first responders’ to an injury. Neutrophils are present at sites of trauma such as a cut, and they are part of the body’s innate response to fighting a tumor. It had been previously shown that poor prognosis in lung cancer and poor response to immunotherapy treatment for lung cancer were associated with high levels of neutrophils.
“The association of high presence of neutrophils with a bad response to immunotherapy means neutrophils might be a target for scientists to develop new treatments to help people who aren’t responding well to currently available drugs,” Oliver suggested. Oliver found that the tumors changed the behavior of the neutrophils, causing inhibition of their normal roles and influencing them to behave in ways that supported tumor growth.