Cell viability assessment in chitosan hydrogel. Schematic representation of chitosan hydrogel preparation and cell and/or MP encapsulation (A). Representative images of mouse splenocytes stained as live (Calcein AM/Green) or dead (EthD/Red) at days 0 and 2 of culture in the complete medium with or without being encapsulated in chitosan hydrogels (B). Representative flow cytometry plots of live/dead staining (C) and frequency of live cells (D) for mouse splenocytes cultured in the complete medium or encapsulated in chitosan hydrogel for 2 d (n = 3 biological replicates). Data are shown as the mean ± SD. As indicated in (B), representative images of live/dead staining of human tumor-infiltrating lymphocytes cultured either in standard medium or embedded in the chitosan hydrogel, both in the presence of IL-2 at days 0, 2, 8, and 14 (E). Credit: Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2409560122

Researchers at Moffitt Cancer Center have developed a novel biomaterial-based system that induces the formation of tertiary lymphoid-like structures (TLSs). These immune cell clusters are increasingly linked to improved outcomes and treatment responses in cancer. Results of their study are 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.

In this interview, Rana Falahat, Ph.D., lead author and research scientist in the Immuno-Oncology Program at Moffitt, discusses this work.

Why are TLSs such an important focus in cancer immunology right now?

The presence of TLSs is increasingly shown to be associated 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.

More information: Rana Falahat et al, Chemokine/cytokine-releasing biomaterials induce in situ tertiary lymphoid–like structures and enhance antitumor immunity, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2409560122

Citation: Q&A: How to spark immune hotspots that attack tumors (2025, November 6) retrieved 6 November 2025 from https://medicalxpress.com/news/2025-11-qa-immune-hotspots-tumors.html

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