Lyophilizable and Multifaceted Toll-Like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy.

Lyophilizable and Multifaceted Toll-Like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy.

Publication date: Oct 07, 2019

The low therapeutic efficacy of current cancer immunotherapy is related to non-immunogenic and immunosuppressive tumor microenvironments (TMEs). To overcome these limitations, both the immune priming of antitumoral lymphocytes and the reprogramming of immunosuppressive factors in TMEs are essential. Here, we suggest a nanoemulsion (NE)-based immunotherapeutic platform that can not only modulate tumor-induced suppression but also induce an effective cell-mediated immune response for T cell proliferation. Multifunctional NEs can be fabricated by integrating the efficacy of NEs as delivery systems and the multifaceted immunomodulation characteristics (i.e. immunostimulation and reprogramming of immunosuppression) of small molecule-based Toll-like receptor 7/8 agonists. Local in situ vaccination of melanoma and cervical tumor models with tumor antigens (protein and peptide) adjuvanted with NE loaded with TLR 7/8 agonists [NE (TLR7/8a)] induced the recruitment and activation of innate immune cells, infiltration of lymphocytes, and polarization of tumor-associated M2 macrophages, which resulted in inhibition of tumor growth and prolonged survival in both primary and re-challenged tumor models. Antibody-depletion experiments also suggested that macrophages, type I IFN (IFN-α and IFN-β), CD8+ T cells, and NK1.1+ cells contributed to the antitumor effect of NE (TLR7/8a). The combination of antitumoral lymphocytes and reprogramming of immunosuppressive TMEs induced by NE (TLR7/8a) treatment evoked a synergistic antitumor immune response with immune checkpoint blockade therapy (anti-PD-1 and anti-PD-L1).

Kim, S.Y., Kim, S., Kim, J.E., Lee, S.N., Shin, I.W., Shin, H.S., Jin, S.M., Noh, Y.W., Kang, Y.J., Kim, Y.S., Kang, T.H., Park, Y.M., and Lim, Y.T. Lyophilizable and Multifaceted Toll-Like Receptor 7/8 Agonist-Loaded Nanoemulsion for the Reprogramming of Tumor Microenvironments and Enhanced Cancer Immunotherapy. 24382. 2019 ACS Nano.

Concepts Keywords
Agonist Tumor
CD8 Inhibition tumor
Cervical Vaccination melanoma
Immune Checkpoint Blockade Vaccination
Immunogenic Immunosuppression
Immunomodulation Immunostimulation
Immunosuppression Immunotherapy
Immunosuppressive Branches of biology
Immunotherapeutic Medicine
Immunotherapy Medical specialties
Innate Immune Cells Immune system
Loaded TLR7
Lymphocytes Immunotherapy
Macrophages Toll-like receptor
Melanoma Immune checkpoint
Nanoemulsion Immunosuppression
NEs Macrophage
NK1 Tumor microenvironment
Peptide
Polarization
Priming
Protein
Receptor
Small Molecule
Synergistic
TLR
Toll Like Receptor
Tumor
Tumor Antigens
Vaccination

Semantics

Type Source Name
gene UNIPROT CD274
gene UNIPROT RPL17
disease MESH growth
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT NES
disease DOID Cancer
disease MESH Tumor
gene UNIPROT TLR7

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