Researchers at the Icahn School of Medicine at Mount Sinai announced on July 16 that they have identified a specialized immune cell responsible for organizing and maintaining powerful immune hubs inside tumors, which play a crucial role in antitumor immunity. The study, published in Science, found that dendritic cell type 1 is essential for building and sustaining structures known as tertiary lymphoid structures (TLSs), which serve as local command centers where the body coordinates attacks against cancer within tumors.
According to the research team, patients whose tumors contain TLSs often live longer and respond better to immunotherapy. However, until now, it was unclear what controlled the formation and maintenance of these protective immune hubs. "Our goal was to understand how these immune structures develop and persist inside tumors," said lead study author Raphael Mattiuz, PhD. "We found that a distinct subset of dendritic cells acts as the organizer, bringing together different immune cells and keeping the local anti-cancer response active. That gives us an important new target for future therapies."
The researchers analyzed tumor samples from patients with lung, liver, colorectal, kidney, and ovarian cancers using advanced imaging techniques capable of visualizing multiple types of immune cells simultaneously. They also used spatial gene analysis to map where genes are active within a tumor and determine where dendritic cells were located and which other immune cells they interacted with.
To test whether dendritic cells were truly responsible for constructing these hubs, investigators developed a mouse model closely reproducing TLSs seen in human cancers. By selectively removing or altering dendritic cells at various stages of tumor development in this model, they demonstrated that these cells are required not only to establish but also to maintain functional TLSs over time.
The findings suggest that dendritic cells do more than alert the broader immune system; once TLSs are established inside a tumor, these specialized cells remain present to coordinate ongoing activity among cancer-fighting T cells and antibody-producing B cells directly on site rather than relying on nearby lymph nodes.
"This study provides a foundation for developing treatments that strengthen the body's own immune defenses against cancer," said senior study author Dr. Miriam Merad. Dr. Mattiuz added, "While more research is needed to understand exactly how these immune hubs eliminate tumors, we now have a road map for exploring therapies that could generate more durable anti-cancer responses and ultimately help prevent cancer from returning."
