A macrophage-neutrophil program drives mammary carcinogenesis The molecular and cellular pathways through which breast cancer evades immunosurveillance remain poorly understood. Recent data from Camargo et al. de…

Thank you@deadoc80.bsky.social for your thoughtful commentary on @cp-trendscancer.bsky.social! This builds upon our data and shows the potential for novel therapeutic startegies targeting the TAM-TAN-tumor cell signaling niche we found.
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Thank you @naturecancer.bsky.social for selecting our study to be featured on the cover of the monthly issue!
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@sandracamargog.bsky.social @orimoskowitz.bsky.social @meravcohen.bsky.social

#Neutrophils #PIC-seq #BreastCancer #TME

Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness - Nature Cancer By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promot...

By integrating single-cell RNA and physically interacting cell sequencing analysis, @meravcohen.bsky.social and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promoting cancer aggressiveness.
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www.nature.com/articles/s43...

Neutrophils take their PICk to promote breast cancer - Nature Cancer Tumor-infiltrating neutrophils can have either pro-tumoral potential or anti-tumoral potential. Physical contact between heterogeneous neutrophils and tumor cells in the tumor microenvironment is now ...

Thank you @soehnleinlab.bsky.social for the beautiful ‘News and Views’ on our manuscript!
@naturecancer.bsky.social @meravcohenlab.bsky.social

www.nature.com/articles/s43...

Thank you!

Neutrophils physically interact with tumor cells to form a signaling niche promoting breast cancer aggressiveness - Nature Cancer By integrating single-cell RNA and physically interacting cell sequencing analysis, here Cohen and colleagues report that neutrophils are enriched in physical crosstalk with breast tumor cells, promot...

We want to thank all our collaborators, editors, reviewers and the funding agencies @erc.europa.eu #ISF #ICRF for their contribution and support in the study. www.nature.com/articles/s43...

To sum up: we uncovered a complex signaling niche driving a more aggressive TME: macrophages recruit neutrophils which physically interact with tumor cells (PICs) inducing proliferation & invasion as well as angiogenesis through PICs-vasculature crosstalk.

Finally, we showed the causality between neutrophil-cancer cell physical crosstalk and tumor cell proliferation and invasion properties. Specifically, in vivo neutrophil depletion during advanced-stage breast cancer resulted in reduced endothelial and epithelial proliferation.

We were fascinated to find that the physical interaction between neutrophils and tumor cells also induces a pro-tumoral gene program of proliferation and invasion, which significantly correlates with worse survival in advanced stage #breastcancer patients.

By integrating ligand-receptor and PIC-seq analyses with functional experiments, we found that neutrophils are recruited to the tumor niche mainly by tumor-activated macrophages, and then send pro-angiogenic signals to the perivascular niche.

In-depth molecular characterization of #neutrophils in the mammary gland revealed highly dynamic states. Importantly, tumor-associated neutrophil states expressed a gene signature setting them apart from blood-circulating neutrophils that was shared across primary tumor sites.

As immune and epithelial cell states were highlighted in the tumor niche, we applied PIC-seq, to molecularly investigate their physical interactions. Surprisingly, we found a significant enrichment of neutrophils in physical crosstalk with tumor cells during advanced carcinoma.

After seeing differences in tissue composition during development, normal adulthood and cancer, we defined cellular niches related to each stage by grouping cell states with similar trends in abundance over time. This allowed us to focus our attention on the tumor niche.

We started by exploring immune/non-immune crosstalk during mammary gland development and cancer to unveil tumor-specific cellular states & interactions. To achieve this, we used the MMTV-PyMT mouse model and performed scRNA-seq and PIC-seq.

We are beyond excited to share the first publication of our lab! We highlight the role of #neutrophils in shaping a more aggressive #TME through physical interactions with #breastcancer cells. The work was led by the talented @sandracamargog.bsky.social & @orimoskowitz.bsky.social 🧵