Dr Alan Ramsay
The ability of cancer cells to modulate the immune microenvironment is now recognised as an important hallmark of disease pathophysiology. Identifying the molecular mechanisms of cancer immune suppression in the laboratory is key to the design of more effective immunotherapeutic treatment strategies.
Our group previously demonstrated that chronic lymphocytic leukemia (CLL) cells induce alterations in global gene expression profiles in patient CD4 and CD8 T cells (J Clin Invest. 2005;115(7):1797-1805). This led to my work identifying a profound T cell immunological synapse formation defect that can be reversed with an immunomodulatory drug lenalidomide (Ramsay AG et al., J Clin Invest. 2008;118(7):2427-2437). This work defined a novel T cell immune dysfunction in cancer and has had a significant impact and influence in the field.
My current research strategy uses small interfering RNA (siRNA), or neutralising antibodies, with 2-part functional screening to identify key cancer cell molecules inducing T cell immune suppression (using CLL as a model cancer). Confocal microscopy and image analysis software is utilized to quantify T cell F-actin immune synapse formation events from experimental cell populations. This work has identified the combinational activity of a number of tumour molecules that have immunosuppressive activity in leukaemias, lymphomas, and solid cancer cells. My research approach includes the use of primary cancer cells, a mouse model of leukaemia, investigating immunomodulatory activity of novel drugs, and patient tissue microarrays.
I believe these results provide important mechanistic insight into immune suppression in cancer and should allow better design of immunotherapeutic strategies that can be used in combination with existing anti-cancer drugs.
I joined the then Institute of Cancer in October 2003 as a Cancer Research UK Postdoctoral Research Fellow with Professor Ian R. Hart and Dr John F. Marshall, investigating tumour cell migration and invasion using the latest cell biology technology (Centre for Tumour Biology).
I then became further involved in translational research by joining Professor John G. Gribben’s research group (2006) working on cancer immunology in leukaemia and lymphoma. My research interests include investigating cancer-induced immune cell dysfunction and repair strategies for immunotherapy. A current project is identifying immunosuppressive signaling interactions between tumour cells and T cells using state-of-the-art cancer immunology, cell biology and imaging techniques.
- 2010 – 2012: European Hematology Association (EHA) Fellowship grant, “Identifying modulators of leukaemia-induced T-cell suppression”: €72,000
- 2011: Grant award from the Mayo Clinic (USA), “Correlative science studies (T cell synapse function) for a clinical trial for leukaemia patients”: $80,000
Ramsay AG, Clear AJ, Fatah R, Gribben JG. Multiple inhibitory ligands induce impaired T-cell immunologic synapse function in chronic lymphocytic leukemia that can be blocked with lenalidomide: establishing a reversible immune evasion mechanism in human cancer. Blood. 2012 Aug 16;120(7):1412-21. 22547582
Ramsay AG, Clear AJ, Kelly G, Fatah R, Matthews J, Macdougall F, Lister TA, Lee AM, Calaminici M, Gribben JG. Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy. Blood. 2009 Nov 19;114(21):4713-20. 19786615
Ramsay AG, Johnson AJ, Lee AM, Gorgün G, Le Dieu R, Blum W, Byrd JC, Gribben JG. Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug. J Clin Invest. 2008 Jul;118(7):2427-37. 18551193
Ramsay AG, Keppler MD, Jazayeri M, Thomas GJ, Parsons M, Violette S, Weinreb P, Hart IR, Marshall JF. HS1-associated protein X-1 regulates carcinoma cell migration and invasion via clathrin-mediated endocytosis of integrin alphavbeta6. Cancer Res. 2007 Jun 1;67(11):5275-84. 17545607
*Gorgun G, *Ramsay AG [*co-first], *Holderried TA, Zahrieh D, Le Dieu R, Liu F, Quackenbush J, Croce CM, Gribben JG. E(mu)-TCL1 mice represent a model for immunotherapeutic reversal of chronic lymphocytic leukemia-induced T-cell dysfunction. Proc Natl Acad Sci U S A. 2009 Apr 14;106(15):6250-5. 19332800
For additional publications, please click here.
Cancer Immunotherapy Group:
|Rewas Fatah||Research Technican|
|John Charles Riches||Clinical Research Fellow
- Review Editor of “Frontiers in Non-Coding RNA”, Review Editorial Board.
- Reviewer for Blood and Leukemia journals.
- Member of the British Association of Cancer Research
- Member of American Society of Hematology (ASH) and European Hematology Association (EHA)
- Fellow of the Higher Education Academy