Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms

Bond, Annalise; Fiaz, Sareen; Rollins, Kirstin; Nario, Jazz Elaiza Q.; Snyder, Erika T.; Atkins, Dixon J.; Rosen, Samuel J.; Granados, Alyssa; Dey, Siddharth S.; Wilson, Maxwell Z.; Morrissey, Meghan A.

doi:10.1016/j.devcel.2024.07.017

Developmental Cell

2024

DOI: 10.1016/j.devcel.2024.07.017

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Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms

Annalise Bond,

Sareen Fiaz,

Kirstin Rollins

et al.

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2024

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Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia

Dooling,

Anlaş,

Tobin

et al. 2024

Preprint

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Macrophages often pervade solid tumors, but their nearest neighbor organization is understudied and potentially enables key functions such as phagocytosis. Here, we observe dynamic macrophage clusters in tumors under conditions that maximize cancer cell phagocytosis and use reductionist approaches to uncover pathways to cluster formation and roles for tumor-intrusive pseudopodia, which we term 'intrudopodia'. Macrophage clusters form over hours on low-adhesion substrates after M1 polarization with interferons, including T cell-derived cytokines, and yet clusters prove fluid on timescales of minutes. Clusters also sort from M2 macrophages that disperse on the same substrates. M1 macrophages upregulate specific cell-cell adhesion receptors but suppress actomyosin contractility, and while both pathways contribute to cluster formation, decreased cortical tension was predicted to unleash pseudopodia. Macrophage neighbors in tumor spheroids indeed extend intrudopodia between adjacent cancer cell junctions - at least when phagocytosis conditions are maximized, and coordinated intrudopodia help detach and individualize cancer cells for rapid engulfment. Macrophage clusters thereby provide a cooperative advantage for phagocytosis to overcome solid tumor cohesion.

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Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia

Dooling,

Anlaş,

Tobin

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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Prior Fc receptor activation primes macrophages for increased sensitivity to IgG via long-term and short-term mechanisms

Cited by 1 publication

References 65 publications

Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia

Clustered macrophages cooperate to eliminate tumors via coordinated intrudopodia

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