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Bacteria-mimicking cancer cells reprogram macrophages via multiple PRR pathways for cancer immunotherapy

ABSTRACT: Although macrophages are a powerful cell-based platform for cancer immunotherapy, their antitumor functions, such as phagocytosis and inflammatory responses, are limited by the immunosuppressive tumor microenvironment. Here, we show that decorating cancer cell membranes with bacteria-derived pathogen-associated molecular patterns (PAMPs) initiates phagocytosis and inflammatory responses of macrophages toward cancer cells involving various pattern recognition receptor signaling. Membrane-attached PAMP nanoparticles maintained their immunostimulatory functions. The phagocytic macrophage fraction increased when coincubated with membrane-decorated cancer cells, along with an increased secretion of inflammatory cytokines. Transcriptome analysis revealed that the response of macrophages to PAMP-decorated cancer cells resembled their response to bacteria. In a mouse model, locally injected membrane-decorating PAMP nanoparticles suppressed tumor growth, and the effect was enhanced in combination with the chemotherapeutic drug doxorubicin. Our findings provide insights into the use of macrophages as a cancer immunotherapy modality.

ORGANISM(S): Mus musculus

PROVIDER: GSE327369 | GEO | 2026/04/13

REPOSITORIES: GEO

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Project description:Dunster2014 - WBC Interactions (Model1) This is a sub-model of a three-step inflammatory response modelling study. The model includes distinct populations of white blood cells namely, macrophages and active and apoptotic neutrophil populations. Neutrophil apoptosis rate is predicted to be crucial for the qualitative nature of the system. This model is described in the article: The resolution of inflammation: a mathematical model of neutrophil and macrophage interactions. Dunster JL, Byrne HM, King JR. Bull. Math. Biol. 2014 Aug; 76(8): 1953-1980 Abstract: There is growing interest in inflammation due to its involvement in many diverse medical conditions, including Alzheimer's disease, cancer, arthritis and asthma. The traditional view that resolution of inflammation is a passive process is now being superceded by an alternative hypothesis whereby its resolution is an active, anti-inflammatory process that can be manipulated therapeutically. This shift in mindset has stimulated a resurgence of interest in the biological mechanisms by which inflammation resolves. The anti-inflammatory processes central to the resolution of inflammation revolve around macrophages and are closely related to pro-inflammatory processes mediated by neutrophils and their ability to damage healthy tissue. We develop a spatially averaged model of inflammation centring on its resolution, accounting for populations of neutrophils and macrophages and incorporating both pro- and anti-inflammatory processes. Our ordinary differential equation model exhibits two outcomes that we relate to healthy and unhealthy states. We use bifurcation analysis to investigate how variation in the system parameters affects its outcome. We find that therapeutic manipulation of the rate of macrophage phagocytosis can aid in resolving inflammation but success is critically dependent on the rate of neutrophil apoptosis. Indeed our model predicts that an effective treatment protocol would take a dual approach, targeting macrophage phagocytosis alongside neutrophil apoptosis. This model is hosted on BioModels Database and identified by: BIOMD0000000616. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Bacteria-mimicking cancer cells reprogram macrophages via multiple PRR pathways for cancer immunotherapy

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