Locally Reprogramming Tumor-Associated Macrophages with Injectable Cryogels
Overview
This project was part of my research at Vanderbilt University with graduate student Sydney Henriques and culminated in a publication in Annals of Biomedical Engineering (2025). As a co-author, I contributed to the design, development, and analysis of a novel immunoengineering strategy to treat breast cancer using cytokine-loaded injectable cryogels.
The core idea was to locally deliver immune-modulating cytokines directly into the tumor microenvironment (TME) in order to reprogram tumor-associated macrophages (TAMs) from an immunosuppressive M2-like state into a pro-inflammatory M1-like state. By shifting the balance of macrophage phenotypes, we aimed to reduce tumor growth and improve T-cell–mediated antitumor responses, while avoiding the toxicities associated with systemic cytokine delivery.
Research Goals
Develop an injectable, macroporous alginate cryogel capable of sustained local release of cytokines
Repolarize TAMs toward an M1 anti-tumor phenotype using IL-12 and IFN-γ.
Recruit M2 macrophages toward the cryogel using the chemoattractant CCL2.
Evaluate efficacy across in vitro, ex vivo, and in vivo breast cancer models.
Key Findings
Macrophage Repolarization: Cryogels successfully reprogrammed TAMs from M2 to M1, both in vitro and ex vivo
Tumor Growth Suppression: Mice treated with cytokine-loaded cryogels showed reduced tumor growth compared to controls
T-Cell Reinvigoration: Treatment decreased T-cell exhaustion (lower TIM3+ and LAG3+ CD8+ T cells), promoting an active anti-tumor response
Systemic Effects: Multi-cryogel treatment shifted macrophage phenotypes in the lungs, suggesting potential to reduce metastasis
Safety: Local delivery minimized systemic cytokine toxicity and avoided liver/kidney damage
Impact
This project demonstrates how immunoengineering biomaterials can reshape the tumor microenvironment to enhance cancer immunotherapy. By providing localized, sustained release of cytokines, injectable cryogels represent a promising therapeutic platform for solid tumors.
Henriques SR, Glass EB, Hoek KL, Chalom OZ, Manning AE, Roy S, Graves DK, Goldstein SM, Hacker BC, Jin R, Rafat M, Hurley PJ, Kennedy LC, Kim YJ, Wilson AJ, Yull FE, Giorgio TD.
Locally Reprogramming Tumor-Associated Macrophages with Cytokine-Loaded Injectable Cryogels for Breast Cancer. Annals of Biomedical Engineering (2025). DOI: 10.1007/s10439-025-03823-x