Triple-negative breast cancer tissue shows overproduction of a cell-surface protein called xCT. Image courtesy Luika Timmerman, PhD.
Cancer treatment has advanced with the advent of immunotherapies that, in some cancers, can overcome tumors’ ability to evade the immune system by suppressing local immune responses. But a new study in mice by UC San Francisco researchers has found that, depending on a cancer’s tissue of origin, tumors cause widespread and variable disruption of the immune system throughout the body, not just at the primary tumor site.
Greater success for immunotherapy regimens will rely on taking these different patterns of immune system disruption into account, they said, and findings from the new study, published online in Nature Medicine on May 25, 2020, are already being investigated in the clinic.
“Different cancers do different things to change the systemic immune system, and immunotherapies that help the patient’s immune system attack cancer may work best when they trigger lasting immune responses throughout the body,“ said the study’s principal investigator, Matthew Spitzer, PhD, an assistant professor of otolaryngology and member of the UCSF Helen Diller Family Comprehensive Cancer Center.
Spitzer’s lab team, including the study’s lead authors, Breanna Allen and Kamir Hiam, both UCSF graduate students, determined the abundance and activity of different types of peripheral immune cells – sampled from blood, bone marrow, spleen and lymph nodes near untreated tumors – in mice with different types of cancer, including brain, colon, pancreatic, skin (melanoma) and breast cancer. They used mass cytometry, a recently refined technique which relies on unique metallic molecular markers and mass spectrometry to quickly quantify and identify dozens of cell types in various states of activation.
Untreated Cancer Changes Immune Response
Spitzer earlier discovered that proliferation of new immune cells originating far from a tumor was required for immunotherapy treatment to be effective. In the new study, his lab team has determined that not only does an untreated cancer changes the way the immune response unfolds both locally and at a distance from the tumor, but also that this disruption of the immune system evolves over time. Remarkably, however, the immune system perturbations tracked by the researchers were reversed when the tumors were surgically removed.
Three distinct types of breast cancer examined in the study caused similar patterns of disruption in peripheral immune sites, while tumors originating in other tissues caused distinctly different changes in the relative abundance and activity of different immune cell types. These differences are likely a reflection of both anatomy and physiology, according to Allen.