Anti-lung cancer: glucose is the key

Cancers are not just made of tumor cells. In fact, as they grow, they develop a whole cell ecosystem in and around them. This “tumor microenvironment” is made up of many cell types, including cells of the immune system, such as T lymphocytes and neutrophils.

The microenvironment of the tumor seems to have attracted a lot of interest from cancer researchers, who are always looking for potential therapeutic targets. When it comes to the immune cells, most of the study focuses on T lymphocytes, which have been the main targets of cancer immunotherapy – a cancer treatment that turns the patient’s own immune system against the tumor.

But there is another type of immune cell in the microenvironment of the tumor that has overlooked its importance in cancer development: neutrophils, which are part of the body’s immediate immune response or “texture” to microbes. The question, currently being debated among scientists, is whether neutrophils help or inhibit tumor growth.

Now, a team of researchers led by Etienne Meylan at the EPFL School of Life Sciences has discovered that neutrophils metabolism determines the tumor-supportive behavior in the development of lung cancer. The study is published in Cancer research, journal of the American Society for the Study of Cancer.

What surprised the scientists is that cell metabolism in cancer becomes unregulated. Being neutrophil experts, they considered the possibility that, when these cells reside within the microenvironment of the tumor, their metabolism may also change, which may affect how they contribute to cancer growth.

Focusing on glucose metabolism in a genetically engineered mouse model of lung adenocarcinoma, the scientists eliminated tumor-associated neutrophils (TANs) and compared them with neutrophils from healthy lungs.

Their findings were surprising: the TANs absorb and metabolize glucose much more efficiently than neutrophils from healthy lungs. The researchers also found that TANs secrete a higher amount of a protein called Glut1, which sits on the surface of the cell and enables increased glucose uptake and utilization.

To understand the importance of Glut1 in neutrophils during the development of lung tumors in vivo, we used a solemn system to remove Glut1 specifically from neutrophils, “says Pierre-Benoit Ancey, the study’s first author.” Using this approach, we identified that Glut1 is essential to extend neutrophil longevity in tumors; without Glut1, we found younger TANs in the microenvironment. “

Using X-ray microtomography to monitor adenocarcinomas, the researchers found that removal of Glut1 from TANs led to a lower tumor growth rate but also increased the effectiveness of radiotherapy, a common treatment for lung cancer. In other words, the ability of TANs to efficiently metabolize glucose appears to provide the tumor with the ability to resist treatment – at least in lung cancer.

The scientists believe that because Glut1 loss reduces the longevity of TAN, their “age” determines whether they play a pro- or anti-tumor role. “Usually, we don’t know how to target neutrophils, because they are so important in innate immunity,” says Etienne Meylan. “Our study shows that their altered metabolism in cancer could be a new Achilles heel for consideration in future treatment strategies. Of course, we are only just beginning to learn about the those interesting cells in cancer. ”

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