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.

SOURCE European Hematology Association