How Malignant Cells in Patients With Chronic Lymphocytic Leukemia Escape T Cell Recognition and Attack

AMSTERDAM, June 15, 2012 /PRNewswire/ --

Dr Alan Ramsay will present findings of a study in patients with Chronic Lymphocytic Leukemia that will contribute to the design of immunotherapeutic strategies leading to the killing of cancer cells at the 17^th Congress of the European Hematology Association in Amsterdam.

T cell activation is essential for immunity including the recognition and killing of abnormal target cells such as cancerous cells. T cell activity is tightly regulated by signaling at the contact site (referred to as the "immune synapse") with a target cell. However, the ability of cancer cells to evade T cell recognition and destruction is an emerging hallmark of disease progression. We have previously demonstrated that tumour cells induce impaired T cell immune synapse signaling and killing function in chronic lymphocytic leukaemia patients. The aim of this study was to identify the molecules that mediate this T cell defect in cancer. We designed and performed laboratory assays to identify that the inhibitory molecules CD200, CD270 (HVEM), CD274 (PD-L1), and CD276 (B7-H3) are co-opted by leukaemia cells to induce impaired T cell synapse signalling. We further show that these inhibitory molecules are highly active and mediate impaired T cell function in both haematological malignancies (including follicular lymphoma) and solid carcinoma cells. Of clinical relevance, we demonstrate that the immunomodulatory drug lenalidomide prevented induction of the T cell activation defect by down-regulating tumour cell inhibitory molecule expression and activity. These results establish a novel immune evasion mechanism whereby cancer cells exploit multiple inhibitory signalling pathways to suppress T cell synapse signalling. These pre-clinical findings should help contribute to the design of immunotherapeutic strategies to specifically block these inhibitory molecules in cancer and to repair T cell recognition and killing of cancer cells.

About the EHA Annual Congress

After 16 congresses and constantly increasing number of delegates, the 17^th Congress of EHA is taking place in Amsterdam. Hematology is a specialty that covers everything to do with blood: its origin in the bone marrow, diseases (in the production) of blood and their treatments. The latest data on research and developments within the wide spectrum of hematology are presented.