Related Experiment Video
Updated: Jan 29, 2026
08:32
Enrichment and Characterization of the Tumor Immune and Non-immune Microenvironments in Established Subcutaneous Murine Tumors
Published on: June 7, 2018
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Reprogramming the melanoma tumor immune microenvironment via combinatorial signal 2/3 gene delivery
Kathryn M Luly1,2,3, Xin Ming Matthew Zhou1,4, Sachin S Surwase1,2,3
1Center for Translational ImmunoEngineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Journal for Immunotherapy of Cancer
|January 27, 2026
Summary
Polymeric nanoparticles delivering key immune signals (signal 2/3) effectively reduced melanoma tumor growth by enhancing immune cell infiltration and antigen presentation. This reprogramming strategy highlights the potential of nanoparticle-based immunotherapy.
Area of Science:
- Immunology
- Nanotechnology
- Oncology
Background:
- Adaptive anti-cancer immunity requires antigen presentation (signal 1), costimulation (signal 2), and immunostimulatory cytokines (signal 3).
- Non-viral gene delivery of these signals offers a strategy to reprogram the tumor microenvironment (TME) and enhance antitumor responses.
Purpose of the Study:
- To investigate the codelivery of signal 2 and signal 3 molecules using poly(beta-amino ester)-based nanoparticles (NPs) in a B16F10 melanoma model.
- To assess the impact of these NPs on the TME and downstream immune responses in vivo.
Main Methods:
- Utilized modular polymeric nanoparticles for codelivery of plasmids encoding various signal 2 and signal 3 molecules.
- Administered NPs to B16F10 melanoma tumors in vivo.
- Assessed immune responses and TME changes using flow cytometry and spatial proteomics (PhenoCycler panel).
Main Results:
- Multiple signal 2/3 NP combinations reduced tumor growth and increased immune cell infiltration, particularly CD8+ T cells and M1 macrophages.
- NPs promoted antigen presentation on tumor cells and antigen-presenting cells (APCs), and induced MHC class I and II expression.
- Spatial analysis revealed NP-driven recruitment of immune cells and formation of CD8+/CD4+/APC triads, crucial for tumor clearance.
Conclusions:
- Modular NP design enables efficient screening of signal 2/3 combinations for melanoma therapy.
- Spatial proteomics is valuable for evaluating local antitumor immune responses.
- Signal 2/3 NPs effectively reprogram the TME, driving signal 1 and productive antitumor immunity.
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