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Article Abstract
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.
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