Frequency and functional characterization of exhausted <scp>CD</scp>8⁺ T cells in chronic lymphocytic leukemia

Abstract

Abstract Objectives The phenotypic and functional properties of Tim‐3 + / PD ‐1 + / CD 8 + cells as exhausted T cells were investigated in chronic lymphocytic leukemia ( CLL ). Methods Frequency of CD 8 + /Tim‐3 + / PD ‐1 + exhausted cells was determined by flow cytometry. For functional analysis, magnetic beads‐isolated CD 8 + 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 CD 8 + T cells was determined using CD 107a degranulation assay. Results The proportion of exhausted CD 8 + T cells was significantly higher in CLL compared to controls. Isolated CD 8 + 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 CD 8 + T cells. Conclusion Targeting immune inhibitory receptors to restore the function of tumor surrounding T cells could be helpful for immunotherapy of CLL .