Raphael Nemenoff, PhD, wants to bring rogue immune cells back to the “light side”.

A University of Colorado Cancer Center study published in The Journal of Immunology shows that cancer co-opts varieties of immune system ‘macrophages’ to promote tumor growth in the most common form of lung cancer.

“Somehow the cancer is able to make the macrophages that are supposed to be destroying it work in its favor,” says Raphael Nemenoff, PhD, investigator at the CU Cancer Center. “Cells in your immune system are being recruited by the cancer cells to help grow and metastasize.”

Macrophages are immune system cells that respond to infection by recognizing and destroying target cells. Previous studies show that macrophages play a role in the way cancer tumors grow and metastasize.

“In several types of cancer it has been seen that macrophage depletion results in slower tumor growth,” says Nemenoff. “This implies that the cells are important when it comes to tumor progression and may also indicate the clinical outcome of a patient.”

The most well-known immune cells are M1 and M2 macrophages. M1 macrophages encourage inflammation and are proposed to inhibit cancer growth. M2 macrophages are proangiogenic, meaning that they encourage the growth of new blood vessels. They are proposed to promote cancer progression. M1/M2 cells are complex and can be divided into distinct, multiple populations that are not well understood, particularly when it comes to their role in cancer.

To see how macrophage varieties affect cancer progression, Nemenoff and colleagues implanted Lewis lung carcinoma (LLC) cells into animal models. Then, once the disease had metastasized, the researchers obtained cancer cells again. The team used RNA-sequencing to profile differences in gene expression between the macrophage populations and determine how they change during tumor progression.

Nemenoff and his team discovered four populations of macrophages present in the lung. One of the populations of macrophages, which they designated MacA, are resident in the lung and do not significantly change in the setting of cancer. The other three populations, named MacB1, MacB2, and MacB3 cells, were recruited to the tumor, and appeared to have an effect on tumor growth. Populations of MacB2 and MacB3 cells increased dramatically with growing tumor size. The population of MacB3 cells increased the most with tumor progression. The team also discovered that MacB3 cells might help the tumor attach to other organs in the body. These populations also appear to have different roles in cancer progression, with MacB2 expressing genes that alter the biophysical properties of the tumor, while MacB3 cells express molecules critical for communication between the cancer cells and the surrounding microenvironment.

“This study indicates that certain populations of macrophages generally aid tumor progression, suggesting that selectively blocking their recruitment may represent a therapeutic strategy to inhibit lung cancer progression,” Nemenoff says.