NKT, MAIT and Foxp3+ cells in the regulation of disease progression in Chronic Lymphocytic Leukemia (CLL). (#82)
Chronic Lymphocytic Leukemia (CLL), a malignancy characterized by the accumulation of mature B cells, is the most common form of leukemia affecting adults in the western world. The disease progression of CLL is unpredictable; patients can remain stable for variable periods (1- 20 years), before rapidly progressing to aggressive and symptomatic disease requiring treatment.
Studies have shown that immune regulation may play an important role in progression of CLL, with increased numbers of Foxp3+ T regulatory cells correlating with disease progression. Other regulatory subsets such as NKT cells and MAIT cells may also be important. NKT cells regulate anti-tumour immunity in a variety of cancer models through the production of cytokines, although their exact role in CLL is poorly understood. MAIT cells are another regulatory T cell population with a semi-invariant TCR repertoire. They are not as well studied in the context of cancer, but interact with B cells and may also regulate immune activity in CLL patients..
Characterization of regulatory T cell subsets in CLL patients at different stages of the disease, including enumeration and analysis of cytokines and cell surface molecules involved in the suppression of T cell immunity will provide important insights about the role of immune regulation in CLL patients and potentially provide new targets for cancer immunotherapy.
Our preliminary results have already identifies several abnormalities in patients with CLL, including a deficiency of MR1 restricted MAIT cells, including the well studied CD161+CD8+ subset.