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Updated: May 5, 2026
Anticancer Efficacy of Photodynamic Therapy with Lung Cancer-Targeted Nanoparticles
Published on: December 1, 2016
In situ-formed immunotherapeutic hydrogel containing sphingosine-1-phosphate for enhanced lung cancer immunotherapy
Hui Shen1,2, Qi Deng3, Zhike Chen2,4
1Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200086, China.
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 demonstrated that S1P-αPDL1@Gel effectively inhibited tumor growth and reduced the recurrence of local tumors after surgery. Additionally, the hydrogel significantly enhanced the infiltration of dendritic cells, M1 macrophages, CD4+ T cells, and CD8+ T cells. S1P-αPDL1@Gel holds a promising therapeutic strategy for remodeling the immunosuppressive tumor microenvironment.
Insights
Sphingosine-1-phosphate (S1P) can overcome resistance to PD-1/PD-L1 cancer therapy by enhancing immune cell infiltration. A novel hydrogel delivering S1P and anti-PD-L1 effectively inhibits tumor growth and recurrence.
Area of Science:
- Immunology
- Oncology
- Biomaterials
Background:
- Limited immune cell infiltration into tumors hinders the effectiveness of immune checkpoint inhibitors (ICIs).
- Sphingosine-1-phosphate (S1P) levels are reduced in non-responsive lung cancer patients undergoing PD-1/PD-L1 therapy.
- S1P gradients are crucial for immune cell migration, viability, and M1 macrophage polarization.
Purpose of the Study:
- To investigate the role of S1P in overcoming resistance to PD-1/PD-L1 therapy.
- To develop a novel drug delivery system for sequential S1P and anti-PD-L1 (αPDL1) release.
- To evaluate the therapeutic efficacy of S1P-αPDL1@Gel in a tumor microenvironment.
Main Methods:
- Analysis of S1P levels in lung cancer patients unresponsive to PD-1/PD-L1 therapy.
- Utilizing a biodegradable sodium alginate hydrogel for sustained and sequential release of S1P and αPDL1.
- In vivo studies to assess tumor growth inhibition, recurrence, and immune cell infiltration.
Main Results:
- S1P down-regulation correlates with non-response to PD-1/PD-L1 therapy in lung cancer.
- S1P promotes immune cell migration and M1 macrophage polarization via ROS-NFκB and JAK-STAT pathways.
- S1P-αPDL1@Gel treatment significantly inhibited tumor growth and reduced local recurrence.
- The hydrogel enhanced infiltration of dendritic cells, M1 macrophages, CD4+, and CD8+ T cells.
Conclusions:
- S1P plays a critical role in enhancing anti-tumor immunity and overcoming ICI resistance.
- The S1P-αPDL1@Gel hydrogel is a promising strategy for remodeling the immunosuppressive tumor microenvironment.
- This approach offers a potential new therapeutic avenue for lung cancer treatment.
