Gamma delta T cell trafficking

Dr Seth Coffelt (Cancer Sciences, University of Glasgow/CRUK Beatson Institute) http://www.beatson.gla.ac.uk/seth_coffelt
Prof Gerry Graham (Immunology, University of Glasgow)

The spread of cancer or metastasis is a terminal disease, as clinicians have very little options to treat cancer patients with metastatic disease. This is due in large part to a lack of understanding about how metastasis occurs. Over the past several years, immune cells have been shown to play a major role in metastasis formation. One immune cell population, called γδ T cells, promotes breast cancer metastasis by working with another immune cell, called neutrophils, to suppress anti-metastatic, cytotoxic T lymphocytes. Therefore, targeting these γδ T cells may prevent breast cancer metastasis. This project will focus on chemokine receptors expressed by γδ T cells as a therapeutic strategy to inhibit metastasis. The student will analyse chemokine receptor expression on γδ T cells and determine which of these receptors is required for trafficking to metastatic organs, such as lung and lymph nodes. The student will use a broad range of techniques including genetically engineered mouse models, metastasis models, flow cytometry, various histological methods, as well as microscopy and imaging. This project may lead to new immunotherapeutic approaches to counteract breast cancer metastasis.

Keywords: Metastasis, Immune cells, Chemokines, γδ T cells

References:

Macrophages and Neutrophils: Regulation of the Inflammatory Microenvironment in Autoimmunity and Cancer. Rahat MA, Coffelt SB, Granot Z, Muthana M, Amedei A. Mediators Inflamm. 2016;2016:5894347.

Neutrophils in cancer: neutral no more. Coffelt SB, Wellenstein MD, de Visser KE. Nat Rev Cancer. 2016 Jul;16(7):431-46.

Revving Up Dendritic Cells while Braking PD-L1 to Jump-Start the Cancer-Immunity Cycle Motor. Coffelt SB, de Visser KE. Immunity. 2016 Apr 19;44(4):722-4.

Immune-mediated mechanisms influencing the efficacy of anticancer therapies. Coffelt SB, de Visser KE. Trends Immunol. 2015 Apr;36(4):198-216.

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Coffelt SB, Kersten K, Doornebal CW, et al., de Visser KE. Nature. 2015 Jun 18;522(7556):345-8.

Spread of Psoriasiform Inflammation to Remote Tissues Is Restricted by the Atypical Chemokine Receptor ACKR2. Shams K, Wilson GJ, Singh M, et al., Graham GJ. J Invest Dermatol. 2016 Aug 26. pii: S0022-202X(16)32274-6.

Atypical Chemokine Receptors and Their Roles in the Resolution of the Inflammatory Response. Bonecchi R, Graham GJ. Front Immunol. 2016 Jun 10;7:224.

Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection. Pingen M, Bryden SR, Pondeville E, Schnettler E, Kohl A, Merits A, Fazakerley JK, Graham GJ, McKimmie CS. Immunity. 2016 Jun 21;44(6):1455-69.

CXCR2 and CXCL4 regulate survival and self-renewal of hematopoietic stem/progenitor cells. Sinclair A, Park L, Shah M, et al., Graham GJ, Pellicano F, Holyoake TL. Blood. 2016 Jul 21;128(3):371-83.

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain. McColl A, Thomson CA, Nerurkar L, Graham GJ, Cavanagh J. J Neuroinflammation. 2016 May 9;13(1):102.

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