Dr Seth Coffelt – Immune Cells and Metastasis
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, pancreatic and colorectal cancers. 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.
Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: neutral no more. Nat Rev Cancer. 2016; 16: 431–446
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: 345-8.
Coffelt SB, de Visser KE. Cancer: Inflammation lights the way to metastasis. Nature. 2014; 507: 48-9.
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: e42217. *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: 4183-90.
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: 907-15. *corresponding author
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
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
Current committee membership
Breast Cancer Now Grants Committee member
Edwards SC, Hedley A, Hoevenaar WHM, Glauner T, Wiesheu R, Kilbey A, Shaw R, Boufea K, Batada N, Blyth K, Miller C, Kirschner K, Coffelt SB. Single-cell analysis uncovers differential regulation of lung γδ T cell subsets by the co-inhibitory molecules, PD-1 and TIM-3. bioRxiv. 2021. doi: https://doi.org/10.1101/2021.07.04.451035
Edwards SC, Hoevenaar WHM, Coffelt SB. Emerging immunotherapies for metastasis. Br J Cancer. 2021;124:37-48.
Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306-2329.
Dhayade S, Pietzke M, Wiesheu R, Tait-Mulder J, Athineos D, Sumpton D, Coffelt S, Blyth K, Vazquez A. Impact of Formate Supplementation on Body Weight and Plasma Amino Acids. Nutrients. 2020; 12(8):2181.
Millar R, Kilbey A, Remak SJ, Severson TM, Dhayade S, Sandilands E, Foster K, Bryant DM, Blyth K, Coffelt SB. The MSP-RON axis stimulates cancer cell growth in models of triple negative breast cancer. Molecular oncology. 2020;14: 1868-1880
Muthalagu N, Monteverde T, Raffo-Iraolagoitia X, Wiesheu R, Whyte D, Hedley A, Laing S, Kruspig B, Upstill-Goddard R, Shaw R, Neidler S, Rink C, Karim SA, Gyuraszova K, Nixon C, Clark W, Biankin AV, Carlin LM, Coffelt SB, Sansom OJ, Morton JP, Murphy DJ. Repression of the Type I Interferon pathway underlies MYC & KRAS-dependent evasion of NK & B cells in Pancreatic Ductal Adenocarcinoma. Cancer discovery. 2020;
Boire A, Coffelt SB, Quezada SA, Vander Heiden MG, Weeraratna AT. Tumour Dormancy and Reawakening: Opportunities and Challenges. Trends in cancer. 2019; 5: 762-765.
Mackey JBG, Coffelt SB, Carlin LM. Neutrophil Maturity in Cancer. Frontiers in immunology. 2019; 10: 1912.
Salvagno C, Ciampricotti M, Tuit S, Hau CS, van Weverwijk A, Coffelt SB, Kersten K, Vrijland K, Kos K, Ulas T, Song JY, Ooi CH, Ruttinger D, Cassier PA, Jonkers J, Schultze JL, Ries CH, de Visser KE. Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response. Nat Cell Biol. 2019; 21: 511-21.
Silva-Santos B, Mensurado S, Coffelt SB. γδ T cells: pleiotropic immune effectors with therapeutic potential in cancer. Nature Reviews Cancer. 2019; 19, 392–404
Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, Henneman L, Kas SM, Prekovic S, Hau CS, Vrijland K, Drenth AP, de Korte-Grimmerink R, Schut E, van der Heijden I, Zwart W, Wessels LFA, Schumacher TN, Jonkers J, de Visser KE. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature. 2019; 572: 538–542
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: eaao2565
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
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
Sarah Edwards (CRUK Glasgow Centre)
Wilma Hoevenaar (Breast Cancer Now)
Toshiyasu Suzuki (Marie Curie Fellowship; Naito Foundation)
Anna Kilbey (CRUK Glasgow Centre)
Clinical Research Fellow
Josip Vrancic (CRUK Glasgow Centre) — co-supervised by Patricia Roxburgh
Liam Hayman (Medical Research Council) - co-supervised by Joanne Edwards and Antonia Roseweir
Mark Lawrence (Pancreatic Cancer UK Future Leaders Academy)
Former Lab Members
Kyla Foster (University of Colorado, Boulder, USA)
Shruthi Lakshmi Arumugam
Erin Morris (Department Chair of Biology & Chemistry, Baker University, Baldwin City, Kansas, USA)
Sarah Jane Remak