Professor Douglas Fearon
Professor Douglas Fearon is pleased to consider applications from prospective PhD students.
Cancer biology and in vivo models
In vivo modelling
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.
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