Abstract
Microbe-based cancer immunotherapy has recently emerged as a hot topic for cancer treatment. However, serious limitations remain including infection associated side-effect and unsatisfactory outcomes in clinic trials. Here, we fabricate different sizes of nano-formulations derived from yeast cell wall (YCW NPs) by differential centrifugation. The induction of anticancer immunity of our formulations appears to inversely correlate with their size due to the ability to accumulate in tumor-draining lymph node (TDLN). Moreover, we use a percolation model to explain their distribution behavior toward TDLN. The abundance and functional orientation of each effector component are significantly improved not only in the microenvironment in tumor but also in the TDLN following small size YCW NPs treatment. In combination with programmed death-ligand 1 (PD-L1) blockade, we demonstrate anticancer efficiency in melanoma-challenged mice. We delineate potential strategy to target immunosuppressive microenvironment by microbe-based nanoparticles and highlight the role of size effect in microbe-based immune therapeutics.
© 2022. The Author(s).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allografts
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Animals
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B7-H1 Antigen / antagonists & inhibitors
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B7-H1 Antigen / genetics
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B7-H1 Antigen / immunology
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Cell Line, Tumor
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Cell Wall / chemistry
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Dendritic Cells / drug effects
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Dendritic Cells / immunology
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Female
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Gene Expression Regulation, Neoplastic
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Immunotherapy / methods*
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Injections, Intralesional
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Lymph Nodes / drug effects*
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Macrophage Activation / drug effects
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Melanoma, Experimental / genetics
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Melanoma, Experimental / mortality
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Melanoma, Experimental / pathology
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Melanoma, Experimental / therapy*
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Mice
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Mice, Inbred C57BL
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Nanoparticles / administration & dosage*
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Nanoparticles / chemistry
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Particle Size
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RAW 264.7 Cells / drug effects
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RAW 264.7 Cells / immunology
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Saccharomyces cerevisiae / chemistry*
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Skin Neoplasms / genetics
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Skin Neoplasms / mortality
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Skin Neoplasms / pathology
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Skin Neoplasms / therapy*
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Survival Analysis
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Syk Kinase / antagonists & inhibitors
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Syk Kinase / genetics
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Syk Kinase / immunology
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Toll-Like Receptor 2 / antagonists & inhibitors
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Toll-Like Receptor 2 / genetics
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Toll-Like Receptor 2 / immunology
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Tumor Burden / drug effects
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Tumor Microenvironment / drug effects
Substances
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B7-H1 Antigen
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Cd274 protein, mouse
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Tlr2 protein, mouse
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Toll-Like Receptor 2
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Syk Kinase
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Syk protein, mouse