How the immune system both encourages and prevents lung cancer

In the United States, lung cancer is the leading cause of cancer-related mortality, with deaths totaling in the millions per year. Multiple treatment methods have been developed, yet overall survival rates for metastasized lung cancer—meaning the cancer has spread to other areas of the body—is less than 10 percent.

Lung cancers are adept at evading the body’s natural defenses, which allows for many lung cancers to go undiagnosed until they metastasize because the disease can progress without symptoms presenting. Understanding how the disease can be cured, or at least controlled, is an urgent task.

Bettina Hoden, a second-year Texas A&M School of Medicine PhD student researching at the Texas A&M Health Institute of Biosciences and Technology (IBT), authored a review article as a way to highlight the burgeoning understanding of how lung cancer immunotherapies function. Immunotherapies take advantage of the mechanics of the immune system in several ways: checkpoint inhibitors turn off the mechanism that prevents immune responses from being too strong, while monoclonal antibodies target their attack to certain portions of a cancer cell.

Hoden’s article goes beyond a surface-level understanding of immunotherapy and instead drills down on a particular type of factor in the immune system response: Toll-like receptors (TLRs), which are molecules found on normal cells and cancer cells alike. TLRs recognize structures that are found on the surfaces of pathogens and activate the immune system’s defenses.

With her mentor, Dekai Zhang, MD, PhD, of the IBT’s Center for Infectious and Inflammatory Disease, Hoden peels back layers of ambiguity and points the way toward furthering the field of Toll-like receptor-based immunotherapies.

The key observation Zhang, Hoden and their co-authors make is as straightforward as it is confounding. Toll-like receptors initiate the immune response. Yet, while each of the nine TLRs discussed in the article suppresses the growth of cancer cells, they can also support tumor growth. Their article, published in the journal Frontiers in Immunology, demonstrates the lack of clarity underlying currently available immunotherapies. Without understanding how immunotherapies function precisely, there will continue to be only a small subset of patients for whom immunotherapies are a viable option.

Even so, when asked about the impact of the review article and what it means that the very systems that are meant to empower our body to eliminate cancers are just as capable of playing the metaphorical Trojan horse and allowing cancer cells to thrive, Hoden was impassioned and clear: “Putting all of these pieces together has opened my eyes to the fact that we have a long way to go.”