Current state of cancer immunity cycle: new strategies and challenges of using precision hydrogels to treat breast cancer

Yingze Zhu ¹ Yanlin Su ¹ Yaxin Guo ¹ Xinyue Wang ¹ Yonggui Xiao ¹ Yonggui Xiao ¹ Hang Yang ² Hui Pang ^1*

• ¹ Harbin Medical University Cancer Hospital, Harbin, China
• ² Tianjin Medical University, Tianjin, Tianjin Municipality, China

The cancer-immunity cycle provides a framework for a series of events in anti-cancer immune responses, initiated by T cell-mediated tumor cell killing, which leads to antigen presentation and T cell stimulation. Current immunomodulatory therapies for breast cancer are often associated with short duration, poor targeting to sites of action, and severe side effects. Hydrogels, with their extracellular matrix-mimicking properties, tunable characteristics, and diverse bioactivities, have garnered significant attention for their ability to locally deliver immunomodulators and cells, providing an immunomodulatory microenvironment to recruit, activate, and expand host immune cells. This review focuses on the design considerations of hydrogel platforms, including polymer backbone, crosslinking mechanisms, physicochemical properties, and immunomodulatory components. The immunomodulatory effects and therapeutic outcomes of various hydrogel systems in breast cancer treatment and tissue regeneration are highlighted, encompassing hydrogel depots for immunomodulator delivery, hydrogel scaffolds for cell delivery, and immunomodulatory hydrogels dependent on inherent material properties. Finally, the challenges that persist in current systems and future directions for immunomodulatory hydrogels are discussed.