This month, in celebration of the 100th anniversary of the American Physiological Society journal Physiological Reviews, we are highlighting recent research published in the journal. Interested in reading more in celebration of Physiological Reviews’ birthday? Read our spotlight on migraine, about bariatric surgery’s effect on hunger and new thoughts on why you can’t sleep.

When we hear the word “cancer,” we often think of tumors—abnormal masses of tissue that grow uncontrollably and do not die when they should. Chemotherapy and other drugs are used to try to get rid of or shrink cancerous tumors.

Research over the past several decades has shown that cancer is complex and involves much more than the cells that make up a tumor. A tumor microenvironment is made up of a variety of cell types, including immune cells, endothelial cells that line the blood vessels, byproducts of metabolic processes—such as lactate and amino acids— and proteins called cytokines that cause and aid in the inflammatory process. This microenvironment influences how fast a tumor progresses and how it responds to therapy.

The tumor microenvironment also greatly influences how the immune system works. The immune system is our disease-fighting “machinery,” but it is also involved with cancer. Interestingly, the immune system can fight tumor progression or contribute to its growth, depending on the type of immune cell and the tumor microenvironment.

To make things even more complicated for cancer researchers, metabolism also plays a pivotal role in how tumors develop and respond to treatment. Some tumors thrive in a low- or no-oxygen environment, while others will grow only when there’s oxygen. This is called the tumor’s “metabolic landscape.”

Research published in Physiological Reviews discusses three targets within the immune system that may be used to develop new cancer treatments.

Immunity

The immune checkpoint system is a way for the body to stop our immune system from responding when there is no threat. However, tumors sometimes co-opt immune checkpoint activity, meaning that the immune system will also fail to recognize and attack cancer cells. The tumor’s microenvironment can also change our immune system activity.

Hypoxia

When there is a lack of oxygen (hypoxia) available in an area of our body, several adaptive processes occur to help us tolerate low oxygen levels in the future. This is why athletes train at high altitude (simulated hypoxia.) While this may be a good thing in some instances, in regard to cancer, low oxygen may also cause a tumor to grow larger. Hypoxia modifies the tumor’s response to the immune system and may make tumors more able to evade the immune system. Blocking the tumor’s response to low-oxygen environments may be a way to treat certain types of cancers.

Metabolism

Scientists used to think that cancer cells used only glucose as a fuel, but recent studies show that cancer cells’ metabolism also uses fatty acid oxidation and other metabolic pathways in the cells’ energy centers (mitochondria). Because healthy cells use the same metabolic pathways as some of these cancer cells, immune cells may fail to recognize abnormal tumor cells.

The concept of “immunometabolism” acknowledges the unique and complex response of the immune system to cancer. By characterizing the tumor microenvironment of each cancer and using treatments targeted at specific immune system pathways, we can potentially develop new treatment strategies for cancer. Potential targeted treatments for cancer using the immune system may include changing how immune cells function in a tumor microenvironment and rewiring the immune system to better recognize cancer cells.

The tools of science and insights of brilliant researchers are continually bringing us closer to one day finding a cure for cancer.