Seth Coffelt – Immune Cells and Metastasis

Introduction

CoffeltS

Understanding how cancer spreads from its primary site of origin to distant organs is one of the major challenges in cancer research. What has become evident in recent years is that mutations in cancer cells are not sufficient to drive metastasis formation – cancer cells need assistance from surrounding healthy cells. Among these various healthy cells, immune cells have emerged as powerful instigators of metastasis formation but, at the same time, immune cells can also prevent cancer cells from spreading.

Our lab focuses on these dichotomous roles of immune cells and how tumours control immune cell behaviour. We study these concepts in the context of breast and ovarian cancer. We are particularly interested in γδ T cells, a rare population of T cells with properties that are distinct from conventional CD4 and CD8 T cells, as γδ T cells can be both pro-tumourigenic and anti-tumourigenic. Our ultimate goal is to understand how γδ T cells and other immune cells participate in the metastatic process and to develop new immunotherapies that counteract metastatic lesions.


Young Glasgow ovarian cancer survivor speaks out about life after the disease

Read the story from the Evening Times here.

Glasgow doctor reveals why he has taken on the city's fight against cancer

Read about Seth's background and move to Glasgow here.

 
 
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University of Glasgow webpage
 
 
 
Other funding:
 
Naito Foundation logo    CRUK Glasgow Centre 
 
     
                      Pancreatic Cancer UK logo           Wellcome Trust logo                Marie Curie logo
 
 
 
 
               Royal Society logo             Tenovus logo

Lab Report

icon Coffelt Lab Report

Key Publications

Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016 Jun 10. doi: 10.1038/nrc.2016.52. [Epub ahead of print]

Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015. 522(7556):345-8. doi: 10.1038/nature14282. PubMed PMID: 25822788; PubMed Central PMCID: PMC4475637.

Coffelt SB, de Visser KE. Cancer: Inflammation lights the way to metastasis. Nature. 2014. 507(7490):48-9. doi: 10.1038/nature13062. 26. PubMed PMID: 24572360.

Al-ofi E, Coffelt SB*, Anumba DO*. Monocyte subpopulations from pre-eclamptic patients are abnormally skewed and exhibit exaggerated responses to Toll-like receptor ligands. PLoS One. 2012;7(7):e42217. doi: 10.1371/journal.pone.0042217PubMed PMID: 22848746.*co-senior author

Coffelt SB, Chen YY, Muthana M, Welford AF, Tal AO, Scholz A, Plate KH, Reiss Y, Murdoch C, De Palma M, Lewis CE. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion. J Immunol. 2011. 186(7):4183-90. doi: 10.4049/jimmunol.1002802. PubMed PMID: 21368233.

Coffelt SB*, Tomchuck SL, Zwezdaryk KJ, Danka ES, Scandurro AB. Leucine leucine-37 uses formyl peptide receptor-like 1 to activate signal transduction pathways, stimulate oncogenic gene expression, and enhance the invasiveness of ovarian cancer cells. Mol Cancer Res. 2009. 7(6):907-15. doi: 10.1158/1541-7786.MCR-08-0326. PubMed PMID: 19491199. *corresponding author

Biography

Education and qualifications

2006: PhD, Interdisciplinary Program in Molecular & Cellular Biology, Tulane University, USA
2000: BA, Biology & Chemistry, Minors in Music & Global Studies, Drury University, USA

Appointments

2016-present: Senior Research Fellow/Beatson Associate, University of Glasgow
2011-2016: Marie Curie Postdoctoral Fellow with Karin de Visser, The Netherlands Cancer Institute, The Netherlands
2008-2011: Postdoctoral Research Associate with Claire Lewis, University of Sheffield, UK
2007-2008: Postdoctoral Fellow with Aline Scandurro, Tulane University, USA
2005-2007: Visiting Scientist with Frank Marini & Michael Andreeff, MD Anderson Cancer Center, USA
2005: Adjunct Professor, Drury University, USA

Honours and awards

British Association for Cancer Research AstraZeneca Young Scientist Frank Rose Award, 2018
Wellcome Trust Seed Award, 2017
Outstanding Staff Member Award, Netherlands Cancer Institute, 2014
Scholar-in-Training Award, AACR Special Conference on Advances in Breast Cancer Research, 2013
Netherlands Cancer Institute Staff Evening Presenter, 2013
Marie Curie Intra-European Fellowship for Career Development, 2011-2013
Exceptional Contribution Award, University of Sheffield, 2010
Top 10 Finalist for MedImmune's Oncology Research Abstract Competition, 2009
Cancer Association of Greater New Orleans' Student Grant, 2005
Tulane Research Days Presenter, 2003

Recent Publications

2018

Kruspig B, Monteverde T, Neidler S, Hock A, Kerr E, Nixon C, Clark W, Hedley A, Laing S, Coffelt SB, Le Quesne J, Dick C, Vousden K, Martins CP, Murphy DJ. The ERBB network facilitates KRAS-driven lung tumorigenesis. Sci Transl Med 2018 10. pii: eaao2565. doi: 10.1126/scitranslmed.aao2565

2017

Carron EC, Homra S, Rosenberg J, Coffelt SB, Kittrell F, Zhang Y, Creighton CJ, Fuqua SA, Medina D, Machado HL. Macrophages promote the progression of premalignant mammary lesions to invasive cancer. Oncotarget 2017; 8: 50731-46

Kersten K, Coffelt SB, Hoogstraat M, Verstegen NJM, Vrijland K, Ciampricotti M, Doornebal CW, Hau CS, Wellenstein MD, Salvagno C, Doshi P, Lips EH, Wessels LFA, de Visser KE. Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of IL1β in tumor-associated macrophages. Oncoimmunology 2017 6: e1334744

Rumney RMH, Coffelt SB, Neale TA, Dhayade S, Tozer GM, Miller G. PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development. PLoS One 2017; 12: e0188591

van Baal J, Van de Vijver KK, Coffelt SB, van der Noort V, van Driel WJ, Kenter GG, Buist MR, Lok C. Incidence of lymph node metastases in clinical early-stage mucinous and seromucinous ovarian carcinoma: a retrospective cohort study. BJOG 2017; 124: 486-94

Walton JB, Farquharson M, Mason S, Port J, Kruspig B, Dowson S, Stevenson D, Murphy D, Matzuk M, Kim J, Coffelt S, Blyth K, McNeish IA. CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity. Sci Rep 2017; 7: 16827

2016

Coffelt SB, de Visser KE. Revving up dendritic cells while braking PD-L1 to jump-start the cancer-immunity cycle motor. Immunity 2016; 44: 722-4

Coffelt SB, de Visser KE. Systemic inflammation: Cancer's long-distance reach to maximize metastasis. Oncoimmunology 2016; 5: e1075694

Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: Neutral no more. Nat Rev Cancer 2016; 16: 431-46

Rahat MA, Coffelt SB, Granot Z, Muthana M, Amedei A. Macrophages and neutrophils: Regulation of the inflammatory microenvironment in autoimmunity and cancer. Mediators Inflamm 2016; 2016: 5894347

2015

Coffelt SB, de Visser KE. Immune-mediated mechanisms influencing the efficacy of anticancer therapies. Trends Immunol. 2015. 36(4):198-216. doi: 10.1016/j.it.2015.02.006. Review. PubMed PMID: 25857662.

Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature. 2015. 522(7556):345-8. doi: 10.1038/nature14282. PubMed PMID: 25822788; PubMed Central PMCID: PMC4475637.

Doornebal CW, Vrijland K, Hau CS, Coffelt SB, Ciampricotti M, Jonkers J, de Visser KE, Hollmann MW. Morphine does not facilitate breast cancer progression in two preclinical mouse models for human invasive lobular and HER2⁺ breast cancer. Pain. 2015. 156(8):1424-32. doi: 10.1097/j.pain.0000000000000136. PubMed PMID: 25734987.

2014

Al-ofi E, Coffelt SB, Anumba DO. Fibrinogen, an endogenous ligand of Toll-like receptor 4, activates monocytes in pre-eclamptic patients. J Reprod Immunol. 2014. 103:23-8. doi: 10.1016/j.jri.2014.02.004. PubMed PMID: 24661950.

Coffelt SB, de Visser KE. Cancer: Inflammation lights the way to metastasis. Nature. 2014. 507(7490):48-9. doi: 10.1038/nature13062. 26. PubMed PMID: 24572360.

Lab Members

Coffelt lab 067 cropped

Post-docs

Sarah Edwards (CRUK Glasgow Centre)
Toshiyasu Suzuki (Marie Curie Fellowship; Naito Foundation)

Scientific Officer

Anna Kilbey (CRUK Glasgow Centre)

PhD Students

Liam Hayman (Medical Research Council) - co-supervised by Joanne Edwards and Antonia Roseweir
Mark Lawrence (Pancreatic Cancer UK Future Leaders Academy)
Sarah Jane Remak (CRUK Glasgow Centre; William Forrest Charitable Trust PhD Research Academy)

Former Lab Members

Kyla Foster (University of Colorado, Boulder, USA)
Erin Morris (Baker University, Baldwin City, Kansas, USA)
Damiano Rami
Robert Wiesheu (Ludwig Maximillian University, Munich, Germany)

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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