[New York, NY July 16, 2026] — Researchers at the Icahn School of Medicine at Mount Sinai have identified the immune cell that acts as the architect and coordinator of powerful immune hubs that form inside tumors and plays a key role in antitumor immunity. This discovery could lead to new strategies for making cancer immunotherapies more effective.
The findings, published in the July 16 online issue of Science [DOI:10.1126/science.ady1678], reveal that a specialized immune cell called dendritic cell type 1 is essential for building and maintaining structures known as tertiary lymphoid structures (TLSs). These organized clusters of immune cells serve as local command centers, or immune "outposts," where the body coordinates attacks against cancer directly within tumors.
Previous research has shown that patients whose tumors contain TLSs often live longer and respond better to immunotherapy. Until now, however, scientists did not know 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," says lead study author Raphael Mattiuz, PhD , Instructor in the lab of Miriam Merad, MD, PhD , at the Icahn School of Medicine. "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.
As part of the experiments, the research team analyzed tumor samples from patients with lung, liver, colorectal, kidney and ovarian cancers using advanced imaging techniques that allowed them to see many different immune cell types at once. They also used spatial gene analysis, which maps where genes are active within a tumor, enabling the scientists to determine exactly where dendritic cells were located and which immune cells they were interacting with.
To test whether dendritic cells were truly responsible for building and maintaining these immune hubs, the investigators developed a new mouse model that closely reproduces the tertiary lymphoid structures seen in human cancers. Using this model, they selectively removed, activated, or genetically altered 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 keep them functioning over time.
The researchers found that dendritic cells do far more than simply alert the immune system to cancer. Once TLSs are established inside a tumor, these cells remain there, continually coordinating immune activity by bringing together cancer-fighting T cells and antibody-producing B cells. Rather than traveling to nearby lymph nodes, they function as on-site managers, sustaining a strong local immune response, say the investigators.
"We were surprised to see that these rare cells become permanent organizers within the tumor itself," Dr. Mattiuz says. "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 where they're needed most."
The findings provide a clearer path toward therapies designed to increase the number or activity of dendritic cells, helping the body build stronger immune hubs inside tumors. Such approaches could potentially improve existing immunotherapies, particularly for patients whose cancers do not respond well to current treatments.
"This study provides a foundation for developing treatments that strengthen the body's own immune defenses against cancer," says senior study author Dr. Merad, the Robin Chemers Neustein Professor of Immunology and Chair of Immunology and Immunotherapy at the Icahn School of Medicine.
"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," Dr. Mattiuz says.
Researchers say the findings provide an important foundation for understanding how the immune system mounts a sustained attack on cancer. They plan to investigate how TLSs generate long-lasting immune protection and whether therapies that activate dendritic cells can enhance immunotherapy, reduce cancer recurrence, and prevent metastasis.
The paper is titled "Dendritic cells control tertiary lymphoid structure development and maintenance in cancer."
To view the full list of authors, funding, and competing interests, see the journal paper at [DOI:10.1126/science.ady1678].
About the Icahn School of Medicine at Mount Sinai
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City’s large and diverse patient population.
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master’s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 470 postdoctoral research fellows.
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 90th percentile of U.S. private medical schools in Sponsored Programs Direct Expenditures per Principal Investigator, according to the Association of American Medical Colleges. More than 6,900 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai.
Science
Experimental study
Human tissue samples
Dendritic cells control tertiary lymphoid structure development and maintenance in cancer
16-Jul-2026