Monitoring the Cascade of Tumor‐specific Immune Response in vivo via Chemoenzymatic Proximity Labeling

Abstract

AbstractMonitoring the highly dynamic and complex immune response remains a great challenge owing to the lack of reliable and specific approaches. Here, we develop a strategy to monitor the cascade of tumor immune response through the cooperation of pore‐forming alginate gel with chemoenzymatic proximity‐labeling. A macroporous gel containing tumor‐associated antigens, adjuvants, and pro‐inflammatory cytokines is utilized to recruit endogenous DCs and enhance their maturation in vivo. The mature DCs are then modified with GDP‐fucose‐fucosyltransferase (GDP‐Fuc‐Fuct) via the self‐catalysis of fucosyltransferase (Fuct). Following the migration of the obtained Fuct‐DCs to the draining lymph nodes (dLNs), the molecular recognition mediated interaction of DCs and T cells leads to the successful decoration of T cells with GDP‐Fuc‐azide through the Fuct catalyzed proximity‐labeling. Therefore, the activated tumor‐specific T cells in dLNs and tumors can be identified through bioorthogonal labeling, opening up a new avenue for studying the immune mechanism of tumors in situ.