Lab Study Uncovers New Findings On How Cancer Cells Hijack The Immune System to Promote Tumor Growth

As tumors develop and grow, individual tumor cells acquire the ability to adapt to changes in the environment that would normally kill the tumor cells. One way they do this is to trick the immune system.

Myeloid-derived suppressor cells (MDSCs) are a class of immune cells that are known to suppress the immune system. It is well known that tumor cells can recruit MDSCs to promote tumor growth by avoiding destruction by the immune system. But, how cancer cells attract MDSCs and interact to cause tumor growth is poorly understood.

A new study led by Dr. Shawn Zhang from the Baylor College of Medicine, and supported in part by BCRF, sheds new light on a well-known pathway and helps to explain one way in which tumor cells hijack MDSCs to promote growth.

In a report published in Nature Cell Biology , Xiang and colleagues identified a novel function of the mTOR pathway in regulating MDSC recruitment and immune suppression by increasing amounts of an immune factor called G-CSF.

The mTOR pathway is a master regulator of cell growth and division. It responds to many different stimuli including the presence or absence of nutrients, the energy the cell needs, and other signaling molecules. Deregulation of the mTOR pathway has been associated with many types of cancer, including breast cancer. However, the complexity of the mTOR pathway, along with the fact that it also functions in normal cells, presents many challenges to targeted therapy.  The present study suggests that combining mTOR therapy with immunotherapy could overcome some of these barriers.

Using laboratory models, Dr. Zhang and his team showed that certain cancer cells that depend on mTOR signaling for growth produce high amounts of a factor called G-CFS, which acts to attract MDSC to the tumor.  The MDSCs in turn stimulate the production of tumor initiating cells, which produce more G-CSF, creating a vicious tumor-promoting cycle. The connection between mTOR and the immune system through G-CSF is a novel finding and sheds new light on how MDSCs work to promote tumor growth.

“Determining that a patient's tumor is using the mTOR pathway would indicate that the cancer cells are more likely to depend on MDSCs for progression. This information suggests for example, that combining mTOR therapies with therapies for MDSCs represent potential therapeutic strategies," Dr. Zhang explained to ScienceNews.

Commenting on this study, Dr. Zhang credited BCRF for providing “the freedom to explore areas where I…[am] deeply interested. We hope this work will provide [the] foundation for novel immunology-related therapies.”

Immunotherapy is an active area of research among BCRF investigators. The newly launched Drug Research Collaborative has generated nearly two-dozen proposals to study various aspects of immunotherapy from basic science to clinical trials. In addition, BCRF is currently funding 24 projects–totaling more than $6.5 million related to cancer immunology and immunotherapies.