Frequency and functional characterization of exhausted CD8+ T cells in chronic lymphocytic leukemia.

OBJECTIVES: The phenotypic and functional properties of Tim-3+ /PD-1+ /CD8+ cells as exhausted T cells were investigated in chronic lymphocytic leukemia (CLL). METHODS: Frequency of CD8+ /Tim-3+ /PD-1+ exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads-isolated CD8+ T cells were stimulated with PHA and PMA/ionocymin to assess their proliferative responses and cytokine production by MTT and ELISA, respectively. Cytotoxic activity of isolated CD8+ T cells was determined using CD107a degranulation assay. RESULTS: The proportion of exhausted CD8+ T cells was significantly higher in CLL compared to controls. Isolated CD8+ T cells from CLL showed functional defects in proliferation, degranulation, and cytokines production. While IL-2, TNF-α, and IFN-γ were significantly lower in CLL patients, IL-10 was higher in the patients group. Patients with progressive clinical stages showed higher frequency and dysfunction of exhausted CD8+ T cells. CONCLUSION: Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL.