Prof Seth Coffelt – Immune Cells and Metastasis
Introduction
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.
EmailResearchers discover key to 'supercharging' breast cancer treatment
Find out more about Seth's recent research in this article by STV News here.
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.
Lab Report
pdf Coffelt Lab Report (84 KB)
Key Publications
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
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
2023-present: Professor, School of Cancer Sciences, University of Glasgow
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
Recent Publications
2024
Dawson A, Zarou MM, Prasad B, Bittencourt-Silvestre J, Zerbst D, Himonas E, Hsieh YC, van Loon I, Blanco GR, Ianniciello A, Kerekes Z, Krishnan V, Agarwal P, Almasoudi H, McCluskey L, Hopcroft LEM, Scott MT, Baquero P, Dunn K, Vetrie D, Copland M, Bhatia R, Coffelt SB, Tiong OS, Wheadon H, Zanivan S, Kirschner K, Helgason GV. Leukaemia exposure alters the transcriptional profile and function of BCR::ABL1 negative macrophages in the bone marrow niche. Nat Commun. 2024;15(1):1090.
Fercoq F, Cairns GS, Donatis MD, Mackey JBG, Floerchinger A, McFarlane A, Raffo-Iraolagoitia XL, Whyte D, Arnott LWG, Nixon C, Wiesheu R, Kilbey A, Brown L, Al-Khalidi S, Norman JC, Roberts EW, Blyth K, Coffelt SB, Carlin LM. Integrin inactivation slows down neutrophils congesting the pre-metastatic lung in a model of breast cancer. bioRxiv. 2024:2024.2003.2019.585724.
Whyte D, Voorde JV, Sumpton D, Dhayade S, Dornier E, Moore M, Novo D, Peters J, Wiesheu R, Mackey JBG, McFarlane AJ, Fercoq F, Fisher S, Caballero CD, Gilroy K, Redmond KL, Mitchell LE, Anderson E, Thomson G, Dzierozynski LN, Saab JJA, Lewis CA, Muir A, Halbrook CJ, Strathdee D, Jackstadt R, Nixon C, Dunne P, Steele CW, Carlin LM, Macpherson IR, Roberts EW, Coffelt SB, Blyth K, Sansom OJ, Norman JC, Clarke CJ. Uridine Phosphorylase-1 supports metastasis of mammary cancer by altering immune and extracellular matrix landscapes of the lung. bioRxiv. 2024:2024.2007.2002.601676.
Wiesheu R, Edwards SC, Hedley A, Hall H, Tosolini M, Fares da Silva MGF, Sumaria N, Castenmiller SM, Wardak L, Optaczy Y, Lynn A, Hill DG, Hayes AJ, Hay J, Kilbey A, Shaw R, Whyte D, Walsh PJ, Michie AM, Graham GJ, Manoharan A, Halsey C, Blyth K, Wolkers MC, Miller C, Pennington DJ, Jones GW, Fournie JJ, Bekiaris V, Coffelt SB. IL-27 maintains cytotoxic Ly6C(+) γδ T cells that arise from immature precursors. Embo j. 2024.
Lupo F, Coffelt SB. Stressed out neutrophils drive metastasis. Immunity. 2024(4):840-842.
2023
Edwards SC, Hedley A, Hoevenaar WHM, Wiesheu R, Glauner T, Kilbey A, Shaw R, Boufea K, Batada N, Hatano S, Yoshikai Y, Blyth K, Miller C, Kirschner K, Coffelt SB. PD-1 and TIM-3 differentially regulate subsets of mouse IL-17A-producing γδ T cells. J Exp Med. 2023;220.:e20211431
Laing S, Kruspig B, Shaw R, Officer-Jones L, Edwards S, McKinven D, Hsieh Y-C, Powley I, Brady N, Pennie R, Kwan R, Lima A, Myrta S, Periyasamy M, Dye IC, Nixon C, Clark G, Junttila MR, Maddalo D, Miller C, Ali S, Fuchter MJ, Nickles D, Kirschner K, Brown RB, Quesne JL, Strathdee D, Coffelt SB, Roberts E, Murphy DJ. ERBB signalling contributes to immune evasion in KRAS-driven lung adenocarcinoma. bioRxiv. 2023:2023.2007.2024.550274.
Suzuki T, Kilbey A, Casa Rodriguez N, Lawlor A, Georgakopoulou A, Hayman H, Yin Swe KL, Nordin A, Cantù C, Vantourout P, Ridgway RA, Byrne RM, Chen L, Verzi MP, Gay DM, Gil Vazquez E, Belnoue-Davis HL, Gilroy K, Kostner AH, Kersten C, Thuwajit C, Andersen DK, Wiesheu R, Jandke A, Blyth K, Roseweir AK, Leedham SJ, Dunne PD, Edwards J, Hayday A, Sansom OJ, Coffelt SB. β-catenin drives butyrophilin-like molecule loss and γδ T-cell exclusion in colon cancer. Cancer Immunology Research. 2023;11: 1137-1155
Quintana JF, Sinton MC, Chandrasegaran P, Lestari AN, Heslop R, Cheaib B, Ogunsola J, Ngoyi DM, Kuispond Swar NR, Cooper A, Mabbott NA, Coffelt SB, MacLeod A. γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection. Nat Commun. 2023;14(1):5279.
Raffo-Iraolagoitia XL, McFarlane AJ, Kruspig B, Fercoq F, Secklehner J, Donatis MD, Mackey JBG, Wiesheu R, Laing S, Hsieh Y-C, Shaw R, Corbyn R, Nixon C, Miller C, Kirschner K, Bain CC, Daniel J. Murphy, Seth B. Coffelt, Carlin LM. γδ T cells impair airway macrophage differentiation in lung adenocarcinoma. bioRxiv. 2023:2023.2009.2014.557344.
Waldron JA, Kanellos G, Smith RCL, Knight JRP, Munro J, Alexandrou C, Vlahov N, Pardo-Fernandez L, Moore M, Gillen SL, Strathdee D, Stevenson D, Warrander FC, Gilroy K, Nixon C, Cadden B, Powley I, Officer-Jones L, Ballantyne F, Hay J, Pennel K, Edwards J, Campbell AD, Ridgway RA, Coffelt SB, Norman J, Quesne JL, Bushell M, Sansom OJ. eIF4A1 is essential for reprogramming the translational landscape of Wnt-driven colorectal cancers. bioRxiv. 2023:2023.2011.2010.566546.
Coffelt SB, Morton JP. LOXL2 in pancreatic tumourigenesis: the complexity of tumour-stromal crosstalk exemplified. Gut. 2023;72:221-222.
Coffelt SB, Suzuki T. The two sides of the γδ T cell coin. Nat Cancer. 2023;10.1038/s43018-023-00587-y.
Coffelt SB, Suzuki T. γδ T cells turn the tables on immune-evasive colon cancer. Med. 2023;4:141-142.
2022
Curio S, Edwards SC, Suzuki T, McGovern J, Triulzi C, Yoshida N, Jonsson G, Glauner T, Rami D, Wiesheu R, Kilbey A, Purcell RV, Coffelt SB, Guerra N. NKG2D signaling regulates IL-17A-producing γδT cells in mice to promote cancer progression. Discovery Immunology. 2022;1:kyac002.
Paterson K, Paterson S, Mulholland T, Coffelt SB, Zagnoni M. Assessment of CAR-T Cell-Mediated Cytotoxicity in 3D Microfluidic Cancer Co-Culture Models for Combination Therapy. IEEE Open J Eng Med Biol. 2022;3:86-95.
van Wagensveld L, van Baal J, Timmermans M, Gaillard D, Borghuis L, Coffelt SB, Rosenberg EH, Lok CAR, Nijman HW, Kooreman LFS, Sanders J, de Bruijn M, Wessels LFA, van der Wiel R, Rausch C, Broeks A, Kruitwagen R, van der Aa MA, Sonke GS, Schouten PC, Van de Vijver KK, Horlings HM. Homologous Recombination Deficiency and Cyclin E1 Amplification Are Correlated with Immune Cell Infiltration and Survival in High-Grade Serous Ovarian Cancer. Cancers (Basel). 2022;14.
Lawrence M, Wiesheu R, Coffelt SB. The duplexity of unconventional T cells in cancer. The International Journal of Biochemistry & Cell Biology. 2022;146:106213.
2021
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.
Johnson SA, Ormsby MJ, Wessel HM, Hulme HE, Bravo-Blas A, McIntosh A, Mason S, Coffelt SB, Tait SWG, Mowat AM, Milling SWF, Blyth K, Wall DM. Monocytes mediate Salmonella Typhimurium-induced tumour growth inhibition in a mouse melanoma model. Eur J Immunol. 2021;14:5965
Paterson K, Zanivan S, Glasspool R, Coffelt SB, Zagnoni M. Microfluidic technologies for immunotherapy studies on solid tumours. Lab Chip. 2021;21:2306-2329.
Edwards SC, Hoevenaar WHM, Coffelt SB. Emerging immunotherapies for metastasis. Br J Cancer. 2021;124:37-48.
McFarlane AJ, Fercoq F, Coffelt SB, Carlin LM. Neutrophil dynamics in the tumor microenvironment. J Clin Invest. 2021;131: ed2021.
2020
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;
2019
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
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: eaao2565
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
Lab Members
Postdoctoral Scientists
Nadia Iqbal
Toshiyasu Suzuki (McNab)
Principal Scientific Officer
Heather Spence (CRUK Career Establishment Award)
Scientific Officers
Anna Kilbey (CRUK Career Establishment Award)
Kyi Lai Yin Swe (Cancer Research Institute CLIP award)
PhD Students
Federico Lupo (CRUK Career Development Award)
Master's Students
Anna Pidoux
Elizabeth Thompson
Former Lab Members
Muhammad Aslam
Sarah Edwards (Senior Scientist, Takeda)
Kyla Foster (University of Colorado, Boulder, USA)
Anastasia Georgakopoulou
Teresa Glauner
Wilma Hoevenaar
Rhona Millar
Erin Morris (Department Chair of Biology & Chemistry, Baker University, Baldwin City, Kansas, USA)
Damiano Rami
Sarah Jane Remak
Josip Vrancic
Robert Wiesheu
