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HCI Lung Cancer Research Reveals New Treatment Targets

Major Types of Lung Cancer

Lung cancer, as we've talked about before, is very common and very deadly. It's frequently caught late and isn't very treatable. Many researchers are dedicated to understanding and treating the disease. One such research lab at Huntsman Cancer Institute has recently made a breakthrough in how we look at lung cancer.

There are many kinds of lung cancer, each with its own unique characteristics. Because each is biologically distinct, treatment differs among them. Understanding how a cancer works means pinpointing vulnerabilities in the mechanism into which a wrench might be thrown. This is called basic research. One of the facets of cancer that researchers try to understand is the environment surrounding cancerous tumors.

Just as with a normal cell, cancer cells are surrounded by all sorts of things, including blood vessels and immune cells. The tumor actually manipulates this environment to better support itself--it can even promote the growth of new blood vessels to feed the cancer cells oxygen and nutrients as the tumor grows. Immune cells sometimes help the tumor and sometimes harm it. These immune cells are what the Oliver lab recently focused on.

Trudy Oliver, principal investigator at the Oliver lab, says, "Essentially, tumors get these immune cells to do their dirty work for them. [...] Most strikingly, different lung tumor types were recruiting different types of immune cells."

One of their key findings is that squamous cell carcinoma tumors recruit considerably more of a specific kind of immune cell than adenocarcinoma tumors do. That immune cell is called a 'neutrophil'. Normally when the body sustains an injury, neutrophils rush to the scene. They are one of the principal ways the body tries to fight cancer.

Scientists already knew that the presence of many neutrophils is associated with low cancer survival and poor response to immunotherapy treatments, despite the fact that the immune cells are trying to kill the cancer. This is because the tumors change how the neutrophils work, manipulating them into helping the cancer cells rather than harming them.

The Oliver lab's findings suggest the neutrophils might be a target for creation of a new drug: perhaps tampering with them might make immunotherapy more effective in these cases where it otherwise doesn't work well. Oliver explains, "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."

Next, Oliver's lab will focus on discovering exactly what the neutrophils do to support the tumors and how that mechanism works--looking for specific ways drugs could interfere.


Trudy Oliver Neutrophil Graphic

Cells live in complex communities called microenvironments, where many different types of cells interact with one another. In cancer, the microenvironment is a place where cancer cells and healthy cells interact. Oliver's study outlines a lung tumors' influence on immune cells in its microenvironment. Represented in illustration A is a lung tumor. The lung tumor’s microenvironment includes many types of healthy cells and cancer cells, in illustration B. Within this microenvironment, lung cancer cells influence immune cells to develop behaviors that support the cancer cell as reflected in illustration C. Figure provided by the Trudy Oliver lab.



A Bad Influence: The Interplay between Tumor Cells and Immune Cells. (2018, October 16). Retrieved from https://huntsmancancer.org/newsroom/2018/10/interplay-between-tumor-cells-and-immune-cells.php 

Lung Cancer. (n.d.). Retrieved from https://www.cancer.org/cancer/lung-cancer.html 

Nishida, N., Yano, H., Nishida, T., Kamura, T., & Kojiro, M. (2006). Angiogenesis in Cancer. Vascular Health and Risk Management,2(3), 213-219. doi:PMC1993983

Oliver, T. G. (2018). The Lineage-Defining Transcription Factors SOX2 and NKX2-1 Determine Lung Cancer Cell Fate and Shape the Tumor Immune Microenvironment. Immunity,49(4), 764-779. doi:10.1016/j.immuni.2018.09.020

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