In situ-formed immunotherapeutic hydrogel containing sphingosine-1-phosphate for enhanced lung cancer immunotherapy.

ABSTRACT: Limited infiltration of immune cells within tumors restricts the therapeutic efficiency of immune checkpoint blockades. Herein, we discover that sphingosine-1-phosphate (S1P) is down-regulated in patients with lung cancer who do not respond to PD-1/PD-L1 therapy. Our findings indicate that S1P gradient enhances the migration and viability of immune cells and promotes the polarization of macrophages toward the M1 phenotype primarily through mitochondrial reactive oxygen species-activated nuclear factor κB and Janus kinase-signal transducers and activators of transcription signaling pathways. To capitalize on these findings, we used a biodegradable sodium alginate hydrogel as a delivery system for the sustained and sequential release of S1P and anti-PD-L1 (αPDL1). In vivo studies demonstrate

SUBMITTER: Shen H 

PROVIDER: S-EPMC12333694 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature