Professor Douglas Fearon

University position

Professor

Professor Douglas Fearon is pleased to consider applications from prospective PhD students.

Departments

Department of Medicine

Email

dtf1000@cam.ac.uk

Home page

http://www.med.cam.ac.uk/html...

Research Themes

Cancer biology and in vivo models

In vivo modelling

Interests

A confocal image of EGFP-positive stromal cells in a B16 melanoma that express fibroblast activation protein-alpha and that mediate local immunosuppression.
A confocal image of EGFP-positive stromal cells in a B16 melanoma that express fibroblast activation protein-alpha and that mediate local immunosuppression.
View image full-size

We are an immunology lab. We study CD8+ T cell differentiation, and immunosuppression within the tumor microenvironment. Since the CD8+ T cell is the primary mediator of anti-tumor immunity, the two themes are related. We have developed mouse models to study (1) the development of the memory CD8+ T cell, and (2) a tumoral stromal cell that is found in all human carcinomas and a variety of other sterile inflammatory lesions. In our CD8+ T cell studies, we have shown that a subset of effector CD8+ T cells maintain a replicative function, which will help us now to consider strategies for preserving this essential aspect of the CD8+ T cell response in adoptive T cell therapy for cancer. For our tumoral stromal cell work, we have just found that conditional ablation of a single stromal cell type abolishes immunosuppression within the tumor microenvironment and permits immunological control of tumor growth. We seek to apply this finding to improving therapeutic tumor vaccination.

Research Focus

Keywords

T lymphocytes

Tumor immunology

Stromal cells

Immunosuppression

Cancer sites

No direct clinical relevance

Equipment

BAC transgenesis, FACS

Cell culture

Confocal microscopy

DNA sequencing

Fluorescence microscopy

Imaging

Immunohistochemistry

In vivo modelling

PCR

Protein purification

Recombinant protein expression

RNAi

Key publications

Heffner M, Fearon DT (2007), “ Loss of T cell receptor-induced Bmi-1 in the KLRG1+senescent CD8+ T lymphocyte”, Proc Natl Acad Sci USA 104:13414–13419

Carr JM, Carrasco MJ, Thaventhiran JED, Bambrough PJ, Kraman M, Edwards AD, Al-Shamkhani A, Fearon DT. (2006), “CD27 mediates interleukin-2-independent clonal expansion of the CD8+ T cell without effector differentiation”, Proc Natl Acad Sci USA 103:19454–19459

Manders PM, Hunter PJ, Telaranta AI, Carr JM, Marshall JL, Carrasco M, Murakami Y, Palmowski MJ, Cerundolo V, Kaech SM, Ahmed R, and Fearon DT. (2005), “BCL6b mediates the enhanced magnitude of the secondary response of memory CD8+ T lymphocytes”, Proc Natl Acad Sci USA 102:7418–7425

Collaborators

Cambridge

Kevin Brindle

David Tuveson