Dr Heather Long is an Associate Professor with a research interest in viral and cancer immunology.
Understanding T cell control of Epstein-Barr virus
Epstein-Barr virus (EBV) is a common herpesvirus that is carried for life following infection. Although infection is usually asymptomatic, EBV is a clinically important virus. Primary infection is associated with infectious mononucleosis and long-term infection is associated with multiple sclerosis and with >200,000 new cancers each year. Our research focuses on understanding how T cells, in particular CD4+ T cells, target EBV and control long-term virus infection. We have discovered many regions of EBV that are targeted by T cells (epitopes). This enabled our lab to pioneer MHCII tetramer technology for single cell analysis of EBV-specific CD4+ T cells in a range of clinical samples. Our group studies the dynamic, functional and metabolic properties of EBV-specific T cells, and investigates the characteristics of resident memory T cells at the site of virus infection. Collectively, these studies improve our understanding of human T cell control of virus infection, which is essential to develop T cell-based treatments for EBV-associated disease.
Post-transplant lymphoproliferative disease (PTLD)
PTLD is a type of B cell lymphoma that develops in transplant patients because the immunosuppressive treatment they need also weakens the immune system’s defence against cancer. Many cases of PTLD are caused by EBV, which reactivates whilst the virus-specific T cell response is suppressed. PTLD is difficult to detect, therefore it is often diagnosed at an advanced stage when it is difficult to treat. Consequently, survival rates for PTLD patients are poor. Working alongside a UK-wide Phase II clinical trial, we have discovered immune signatures that are only present in those transplant patients that develop PTLD. We are currently validating these signatures in independent cohorts of PTLD patients, with a view to developing a predictive model for early detection of disease. In parallel, we are studying immunity inside PTLD tumours, to identify mechanisms of immune evasion within the tumour microenvironment that prevent T cell destruction. Together, we aim to identify biomarkers for disease detection and uncover novel potential therapeutic targets, thereby improving survival for patients with PTLD.
SARS-CoV-2
Upon the emergence of SARS-CoV-2, we sought to determine how virus-specific T cell immunity was impacted by ongoing viral mutations. We demonstrated that emerging variants of concern contained mutations in several CD4+ T cell epitopes that abolished T cell recognition. In collaboration with Cardiff University, using structural analysis, we described two novel mechanisms of T cell evasion by SARS-CoV-2. Our ongoing work is studying T cell immunity against regions of SARS-CoV-2 that are the most conserved among the family of existing human coronaviruses. Targeting these regions may provide pan-coronavirus protection against current and emerging viruses.
Collaborative research in Cancer Immunology
Our group is involved in the immunological aspects of several collaborative studies in cancer including childhood PTLD, EBV-associated T/NK cell disease and lung cancer. In addition, ongoing collaborative work with Dr Fedor Berditchevski has discovered a novel mechanism of B cell recruitment into breast cancer.