Macrophages, key regulators of tissue health and immune defense, are among the most abundant immune cells in solid tumors. Their role in cancer has been difficult to define because even closely related macrophage populations can have very different, and sometimes opposing, functions.
Funded by the National Institutes of Health’s National Heart, Lung, and Blood Institute, researchers at Geisel School of Medicine, led by principal investigator Claudia Jakubzick , PhD, professor of microbiology and immunology, set out to determine which macrophages help coordinate anti-tumor immunity, which ones support tumor growth, and whether those functions can be selectively targeted.
Using single-cell sequencing and spatial transcriptomics through Dartmouth’s Genomic and Molecular Biology Shared Resources, the team found that important functional differences exist even within macrophage populations that appear similar, and that these differences can be selectively manipulated.
“Our research shows that within each macrophage population, there are both accelerators and brakes,” Jakubzick explains. “We found that macrophages help direct immune cells in ways that can either drive inflammatory responses that fight tumors or promote reparative processes that support tumor development.
“Every cell has the same instruction book, but not every cell reads the same pages,” she says. “The genes a cell turns on reveal the job it is doing in the body. Single-cell sequencing helps scientists see how cells work together in health and how that balance changes in disease. Xenium, a spatial transcriptomics technology, helps us see where those cells are positioned within tissue and the tumor microenvironment.”
Most immune-based cancer treatments act broadly, affecting entire groups of immune cells rather than selectively targeting the specific cells within those groups that help tumors grow. This study points to a more precise strategy: block the immune cells that suppress anti-tumor responses while preserving or strengthening those that help fight the cancer.
In their paper, “ Chemokine-defined macrophage niches establish spatial organization of tumor immunity ,” published in Nature Immunology , lead author Soubhik Ghosh, PhD, a postdoctoral fellow in Jakubzick’s lab, shows that macrophages help shape where immune cells are located within tumors. The team found that some macrophage-driven signals recruit cells that support anti-tumor immunity, while others attract reparative cells that can help tumors persist. In a cancer vaccine model, blocking these suppressive “brakes” with maraviroc significantly improved anti-tumor immunity.
Because maraviroc is already FDA-approved for HIV, these findings may help speed translation to cancer therapy. Although the study focused on lung cancer, Jakubzick says the broader principle may extend to many tumor types and improve cancer vaccine strategies more broadly; better treatments may come from precisely targeting harmful immune programs rather than eliminating entire immune cell populations.
Nature Immunology
Experimental study
Cells
Chemokine-defined macrophage niches establish spatial organization of tumor immunity
23-Mar-2026
The authors declare no competing interests.