Cancer tumors are surrounded by immune cells, but not all of those cells help the body fight back. Some support anti-cancer immunity, while others can unexpectedly help tumors survive.
A new study led by Claudia Jakubzick, PhD, a member of the Dartmouth Cancer Center Immunology & Cancer Immunotherapy Research Program , shows that where immune cells are located within a tumor can reveal whether they are helping or hurting the anti-cancer response.
The study , published in Nature Immunology, focused on macrophages, immune cells best known for clearing debris and responding to injury or infection. In tumors, however, macrophages have been difficult to understand because they are not all the same, even when they look similar and share commonly used surface markers.
"We show that macrophages are not simply 'good' or 'bad,'" says Jakubzick. "Different macrophage populations can play very different roles depending on where they are, where they came from, and the signals they produce."
The study found that one group of resident macrophages, located near airways and blood vessels in the lung, produced signals that attracted other immune cells and helped organize local anti-tumor activity. When these macrophages were removed in preclinical models, tumors progressed more rapidly. By contrast, another macrophage population accumulated deep within tumor regions and helped create an environment that supported tumor progression.
"This work helps explain why past efforts to pan-target macrophages in cancer have had mixed results," Jakubzick said. "If you remove all macrophages, you also eliminate the ones helping the immune system respond."
Although the work is still at an early stage, the findings point to a new direction for cancer immunotherapy. Rather than broadly eliminating macrophages, future therapies may be more effective if they preserve macrophages that help organize anti-cancer immunity while selectively blocking those that protect the tumor.
