Biomaterial-mediated immunomodulation of regulatory T cells in cancer

Immunosuppressive cancers are characterized by tumor microenvironments (TME) that actively inhibit anti-tumor immune responses. Regulatory T cells (Tregs) within the TME are major players in this disruption, owing to their enhanced suppressive capabilities. Thus, targeting this population may be the key to the success of cancer immunotherapies that fail in certain patients. Notably, Tregs play a critical role in immune homeostasis; therefore, strategies to modulate their function must prioritize selective modulation to reduce the risk of unwanted autoimmunity. Biomaterials are versatile platforms for addressing this therapeutic challenge, as they enable spatiotemporal delivery of immunomodulatory agents with reduced unwanted side effects. This review focuses on emerging biomaterials strategies that leverage tunable biomaterial properties to disrupt key metabolic, transcriptional, and signaling pathways central to Treg-mediated immunosuppression in cancer. In addition, we review key experimental methods used to assess Treg modulation in current preclinical studies and provide commentary on the remaining gaps in the field of biomaterials-mediated Treg modulation in cancer.