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Dr. Mikala Egeblad - NETs in flames: neutrophil extracellular traps in cancer and COVID-19

 

Mikala Egeblad

Cold Spring Harbor Laboratory, Cancer Center, New York, NY

NETs in flames: neutrophil extracellular traps in cancer and COVID-19

We study how interactions between cancer cells and their immune microenvironment regulate the metastatic spread of cancer. During the last year, we have also applied our knowledge of innate immune cell functions to studies of the pathophysiology of COVID-19.

We previously identified a novel mechanism by which cancer cells can hijack innate immune cells to promote metastasis, showing that triple negative breast cancer cells activate neutrophils to form metastasis-promoting neutrophil extracellular traps (NETs). Next, we found that when NETs are activated as part of a sustained inflammatory response, they can drive re-initiation of proliferation of quiescent, disseminated tumor cells. At the seminar, I will discuss our recent unpublished discovery that exposure to chronic stress response can promote metastasis through excessive NET formation, and I will discuss some of the underlying mechanisms.

With the onset of the COVID-19 pandemic, we realized that COVID-19 had critical similarities to that of pathologies that are well documented to involve excess NET formation, including acute respiratory distress syndrome and immunothrombosis. Our lab spearheaded the publication of a Perspective that was the first to describe the rationale and opportunities for targeting NETs in COVID-19. At the seminar, I will discuss work we did in collaboration with several other groups of neutrophil biologists to demonstrate NETs in blood and tissues from patients with severe COVID-19, including the presence of NETs as components of atypical microthrombi. I will also discuss unpublished data using SARS-CoV-2 infected golden hamsters to determine the effects of excessive NET formation in lung injury.

Selected references

  • Park, J. et al. (2016) Cancer cells trigger neutrophils to induce metastasis-supporting extracellular DNA traps. Sci Transl Med 8, 361ra138
  • Albrengues, J. et al. (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science pii: eaao4227
  • Zuo, Y. et al. (2020) Neutrophil extracellular traps in COVID-19. JCI Insight 5:138999
  • Middleton, E.A. et al. (2020) Neutrophil extracellular traps (NETs) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 136:1169-1179
  • Barnes, B.J. et al. (2020) Targeting potential drivers of COVID-19: Neutrophil extracellular traps. J Exp Med 217(6):e20200652
  • He X.-Y. et al. (2020) Gut feelings block the flow: microbiota links stress to vascular disease. Immunity, 53:238-240
  • Ackermann, M. et al. (2021) Patients with COVID-19: in the dark-NETs of neutrophils. Cell Death Differ doi: 10.1038/s41418-021-00805-z

Contact: Catherine Muller (Catherine.Muller@ipbs.fr)

Link to attend the seminar: https://meet.starleaf.com/4216820566/app

15 Jun

16:00 - 17:00

Online seminar