Moffitt Study Reveals Way to Spark Immune Hotspots That Attack Tumors

Moffitt Study Reveals Way to Spark Immune Hotspots That Attack Tumors

Key Highlights

• New biomaterial platform: The system uses a biodegradable chitosan-based hydrogel combined with lipid-coated microparticles that release immune-stimulating chemokines over time.

• Immune structure formation: When injected in mice, the formulation triggered local accumulation of immune cells that organized into TLS-like structures similar to those found in tumors.

• Enhanced antitumor response: Mice with induced TLS-like structures exhibited slower tumor growth and an increased presence of tumor-specific T cells, demonstrating potent immune activation.

• Clinical potential: This model provides a powerful new tool for studying TLS biology and could lead to therapies that stimulate TLS formation in tumors that currently resist immunotherapy.

TAMPA, Fla. (Nov. 6, 2025) - Researchers at Moffitt Cancer Center have developed a novel biomaterial-based system that induces the formation of tertiary lymphoid-like structures, or TLSs. These immune cell clusters are increasingly linked to improved outcomes and treatment responses in cancer. Results of their study was published in the Proceedings of the National Academy of Sciences.

TLSs are specialized immune structures that sometimes form within tumors, helping the immune system recognize and attack cancer cells. However, many tumors lack these structures, which can limit the effectiveness of immunotherapy. Understanding how TLSs form and function has been challenging because traditional laboratory models cannot easily reproduce them.

Using an innovative approach, researchers created a biodegradable, injectable hydrogel that slowly releases immune-signaling molecules, including chemokines and cytokines, beneath the skin. These signals attract key immune cells such as T cells and B cells to the injection site, where they self organize into TLS-like structures. When tested in mice, these induced immune clusters supported the activation of tumor-targeting T cells and slowed tumor growth.

Q&A with Rana Falahat, Ph.D., lead author and research scientist in the Immuno-Oncology Program at Moffitt.

Why are TLSs such an important focus in cancer immunology right now?
The presence of TLSs is increasingly shown to associate with better patient outcomes and improved responses to immunotherapies, making them a key focus in cancer immunology research today.

What challenges exist in studying TLSs in the lab, and how does your model help overcome those challenges?
The origins and functions of TLSs in antitumor immunity remain poorly understood, mainly because suitable mouse models have been lacking. In this study, we developed a biomaterial-based system that induces TLS-like structures in a controlled way, which can be used both as preclinical models to study how TLSs form and function within tumors and as platforms to explore new therapeutic strategies that harness these structures to boost antitumor immunity.

Can you explain, in simple terms, how your biomaterial system works?
We designed biodegradable materials that release immune-signaling molecules, such as chemokines and cytokines, after being injected under the skin. These signals attract immune cells, like T cells and B cells, to the site, where they begin to organize into structures that resemble TLSs found in tumors, allowing us to study how these structures form and function.

How might this research eventually benefit cancer patients, especially those whose tumors lack TLSs?
Tumors without TLSs often resist immunotherapy. By learning how to trigger TLS formation, we hope to help the immune system better recognize and attack these tumors, improving treatment options for patients who currently have limited responses to immunotherapies.

This study was supported by the National Cancer Institute (P30-CA076292, P50-CA168536), the CJG Fund, Chris Sullivan Fund, V Foundation, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation and the Melanoma Research Foundation.

About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 58 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, X, Instagram and YouTube.

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