Researchers at the Icahn School of Medicine at Mount Sinai have identified immune cells that form within tumors and act as builders and regulators of powerful immune hubs that play a key role in anti-tumor immunity. This discovery could lead to new strategies to make cancer immunotherapy more effective.
The findings were published online on July 16th. science (DOI:10.1126/science.ady1678) revealed that specialized immune cells called dendritic cell type 1 are essential for the construction and maintenance of structures known as tertiary lymphoid structures (TLS). These organized clusters of immune cells act as local command centers, or immune “outposts,” where the body coordinates its attack on cancer directly within the tumor.
Previous studies have shown that patients with tumors containing TLS often live longer and respond better to immunotherapy. But until now, scientists didn’t know what controls the formation and maintenance of these protective immune hubs.
“Our goal was to understand how these immune structures develop and persist within tumors,” says study lead author Rafael Mathis, Ph.D., instructor in the lab of Miriam Mellado, M.D., at the Icahn School of Medicine. “We discovered that different subsets of dendritic cells act as organizers, bringing together different immune cells and keeping local anti-cancer responses active. This provides important new targets for future therapies.”
As part of the experiment, the researchers analyzed tumor samples from patients with lung, liver, colorectal, kidney, and ovarian cancers using advanced imaging techniques that allow them to see different types of immune cells at once. They also used spatial genetic analysis to map where genes were active within the tumor, allowing them to determine exactly where dendritic cells were located and which immune cells they were interacting with.
To test whether dendritic cells are indeed involved in building and maintaining these immune hubs, the researchers developed a new mouse model that closely reproduces the tertiary lymphoid structures found in human cancers. Using this model, they selectively ablated, activated, or genetically modified dendritic cells at different stages of tumor development. These experiments showed that dendritic cells are required not only to establish these immune hubs but also to maintain their function over time.
Researchers have discovered that dendritic cells do more than just alert the immune system to cancer. Once TLS is established within a tumor, these cells remain there and continuously coordinate immune activity by linking cancer-fighting T cells with antibody-producing B cells. Rather than traveling to nearby lymph nodes, they act as on-site stewards, maintaining a strong local immune response, the researchers say.
We were surprised to see that these rare cells become permanent organizers within the tumor itself. They not only activate cancer-killing T cells; It also helps coordinate antibody responses, allowing multiple parts of the immune system to work together where they are needed most. ”
Raphael Mattiuz, Ph.D., senior study author, instructor in the lab of Miriam Merad, M.D., Icahn School of Medicine
This discovery provides a clearer path to treatments designed to increase the number or activity of dendritic cells and help the body build a powerful immune hub within tumors. Such an approach could improve existing immunotherapies, especially for cancer patients who do not respond well to current treatments.
“This study provides the basis for developing treatments that strengthen the body’s own immune defenses against cancer,” said Dr. Mellado, senior author of the study, the Robin Chemers Neustein Professor of Immunology and professor of immunology and immunotherapy at the Icahn School of Medicine.
“More research is needed to understand exactly how these immune hubs eliminate tumors, but we now have a roadmap to explore treatments that can generate more durable anti-cancer responses and ultimately help prevent cancer recurrence,” says Dr. Mathis.
Researchers say this discovery provides an important basis for understanding how the immune system mounts a sustained attack against cancer. They plan to investigate how TLS generates long-lasting immune protection and whether treatments that activate dendritic cells can enhance immunotherapy, reduce cancer recurrence, and prevent metastasis.
sauce:
Mount Sinai Health System
Reference magazines:
Mathias, R. others. (2026) Dendritic cells control the development and maintenance of tertiary lymphoid structures in cancer. science. DOI: 10.1126/science.ady1678. https://www.science.org/doi/10.1126/science.ady1678
