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 17th 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 17th 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
