Cancer cells are surrounded by immune cells, blood vessels, chemical signals and a support matrix—collectively, the tumor microenvironment. Most microenvironments help tumors grow and metastasize, but some can restrict tumors. My lab studies how to target the bad microenvironments and support the good ones to combat cancer.
Mikala Egeblad and colleagues study cancer and, in particular, the microenvironment in which the cancer cells arise and live. Solid tumors are abnormally organized tissues that contain not only cancer cells, but also various other stromal cell types and an extracellular matrix, and these latter components constitute the microenvironment. Communications between the different components of the tumor influence its growth, its response to therapy, and its ability to metastasize. Among the tumor-associated stromal cells, the lab’s main focus is on myeloid-derived immune cells, a diverse group of cells that can enhance angiogenesis and metastasis and suppress the cytotoxic immune response against tumors. Egeblad is interested in how different types of myeloid cells are recruited to tumors and how their behaviors—for example, their physical interactions with cancer cells and other immune cells—influence cancer progression, including metastasis. The Egeblad lab studies the importance of the myeloid cells using mouse models of breast and pancreatic cancer and real-time imaging of cells in tumors in live mice. This enables them to follow the behaviors of and the interactions between cancer and myeloid cells in tumors during progression or treatment. This technique was instrumental when the lab showed that cancer drug therapy can be boosted by altering components of the tumor microenvironments, specifically reducing either matrix metalloproteinases (enzymes secreted by myeloid cells) or chemokine receptors (signal receptors on myeloid cells). Most recently, the Egeblad lab has showed that when a specific type of myeloid cell, called neutrophil, is activated during inflammation it can awaken sleeping cancer to cause cancer recurrence. The neutrophils do so by forming so-called neutrophil extracellular traps, structures of extracellular DNA and these alter the extracellular matrix surrounding the sleeping cancer cells to provide a wake-up signal.
Cold Spring Harbor Laboratory: Science is hope
December 21, 2020
The Laboratory is a leading research center for genetics, cancer, plant biology, quantitative biology, and neuroscience.
Cancer researchers discuss COVID-19’s effect on the field
July 27, 2020
Dr. David Tuveson and Dr. Tobias Janowitz discuss in Cancer Discovery how the COVID-19 pandemic has changed cancer research.
How two CSHL programs adapted during the COVID-19 pandemic
July 16, 2020
Mikala Egeblad and David Micklos presented their work at the “Life Science Across the Globe” seminar series.
How breast cancer cells sneak past local immune defenses
July 15, 2020
Breast cancer cells sabotage nearby immune cells to evade detection and destruction by the body’s defenses.
CSHL joins “Life Science Across the Globe” seminar series
June 29, 2020
CSHL will present two talks at the “Life Science Across the Globe” seminar series on July 8.
New evidence for how blood clots may form in very ill COVID-19 patients
June 29, 2020
The amount of NETs in COVID-19 patients’ blood vessels correlates with the severity of their disease.
How an antiviral immune reaction can go too far
May 23, 2020
White blood cells sacrifice themselves to ensnare invaders in a sticky NET (neutrophil extracellular trap), but in COVID-19, NETs may hurt us.
What do these scientist moms do? Ask their kids.
May 8, 2020
We asked the children of three scientists to describe their mother’s work. See what they had to say.
How NETs harm lungs
April 23, 2020
Are NETs present in human ARDS, like during fulminant coronavirus infections? Could breaking up NETs help cure patients?
Global NETwork studies role of immune cells in COVID-19 deaths
April 16, 2020
The symptoms of severe COVID-19 disease may be caused by overactive white blood cells that produce gauzy webs of DNA laced with toxic enzymes called NETs.
Fein, Miriam R and He, Xue-Yan and Almeida, Ana S and Bružas, Emilis and Pommier, Arnaud and Yan, Ran and Eberhardt, Anaïs and Fearon, Douglas T and Van Aelst, Linda and Wilkinson, John Erby and Dos Santos, Camila O and Egeblad, Mikala (2020) Cancer cell CCR2 orchestrates suppression of the adaptive immune response.. Journal of Experimental Medicine, 217(10) Rockefeller University Press.
Middleton, EA and He, X.-Y. and Denorme, F and Campbell, RA and Ng, D. and Salvatore, S. and Mostyka, M and Baxter-Stoltzfus, A. and Borczuk, A. and Loda, M. and Cody, MJ and Manne, BK and Portier, I and Harris, E and Petrey, AC and Beswick, EJ and Caulin, AF and Iovino, A and Abegglen, LM and Weyrich, AS and Rondina, MT and Egeblad, M. and Schiffman, JD and Con Yost, C (2020) Neutrophil Extracellular Traps (NETs) Contribute to Immunothrombosis in COVID-19 Acute Respiratory Distress Syndrome. Blood,
Barnes, B.J. and Adrover, J.M. and Baxter-Stoltzfus, A. and Borczuk, A. and Cools-Lartigue, J. and Crawford, J.M. and DaBler-Plenker, J. and Guerci, P. and Huynh, C. and Knight, J.S. and Loda, M. and Looney, M.R. and McAllister, F. and Rayes, R. and Renaud, S. and Rousseau, S. and Salvatore, S. and Schwartz, R.E. and Spicer, J.D. and Yost, C.C. and Weber, A. and Zuo, Y. and Egeblad, M. (2020) Targeting Potential Drivers of COVID-19: Neutrophil Extracellular Traps. J Exp Med, 217(6) pp. e20200652.
Albrengues, J. and Shields, M. A. and Ng, D. and Park, C. G. and Ambrico, A. and Poindexter, M. E. and Upadhyay, P. and Uyeminami, D. L. and Pommier, A. and Kuttner, V. and Bruzas, E. and Maiorino, L. and Bautista, C. and Carmona, E. M. and Gimotty, P. A. and Fearon, D. T. and Chang, K. and Lyons, S. K. and Pinkerton, K. E. and Trotman, L. C. and Goldberg, M. S. and Yeh, J. T. and Egeblad, M. (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science, 361(6409)
Park, J. and Wysocki, R. W. and Amoozgar, Z. and Maiorino, L. and Fein, M. R. and Jorns, J. and Schott, A. F. and Kinugasa-Katayama, Y. and Lee, Y. and Won, N. H. and Nakasone, E. S. and Hearn, S. A. and Kuttner, V. and Qiu, J. and Almeida, A. S. and Perurena, N. and Kessenbrock, K. and Goldberg, M. S. and Egeblad, M. (2016) Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci Transl Med, 8(361) pp. 361ra138.Additional materials of the author at
CSHL Institutional Repository