Deep inside some tumors, the body wages war against cancer using miniature command centers built right at the battlefield. Now, scientists at Mount Sinai in New York have discovered which immune cell acts as the architect of these hidden fortresses — and that discovery could help make cancer treatments work better for more people.
The research team at the Icahn School of Medicine found that a specialized immune cell called dendritic cell type 1 builds and maintains structures called tertiary lymphoid structures, or TLSs. These are organized clusters of immune cells that form inside tumors, acting like local headquarters where the body coordinates attacks against cancer.
“We found that a distinct subset of dendritic cells acts as the organizer, bringing together different immune cells and keeping the local anticancer response active,” said lead author Raphael Mattiuz, Ph.D. “That gives us an important new target for future therapies.”
For years, doctors have known that patients whose tumors contain these TLS structures tend to live longer and respond better to immunotherapy. But nobody understood what actually controlled whether these protective hubs formed or disappeared.
To find answers, the researchers studied tumor samples from patients with lung, liver, colorectal, kidney, and ovarian cancers. They used advanced imaging techniques that let them see many different immune cell types at once, along with spatial gene analysis, which maps where genes are active within a tumor. This helped them pinpoint exactly where the dendritic cells were working and which other immune cells they were talking to.
The team also created a new mouse model that closely mimics how TLSs develop in human cancers. By selectively removing, activating, or genetically altering dendritic cells at different stages of tumor growth, they proved these cells are essential not just for starting the immune hubs, but for keeping them running over time.
The scientists were surprised to discover that dendritic cells do far more than sound an alarm. Once TLSs are established, these cells stay in place as permanent organizers, bringing together cancer-fighting T cells and antibody-producing B cells to sustain the body’s defenses where they’re needed most.
“We were surprised to see that these rare cells become permanent organizers within the tumor itself,” Mattiuz said. “They don’t just activate cancer-killing T cells. They also help coordinate antibody responses, allowing multiple parts of the immune system to work together.”
The findings give researchers a clearer roadmap for developing treatments that could strengthen these natural immune hubs inside tumors. For patients whose cancers don’t respond well to current immunotherapies, this discovery opens a promising new avenue.