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Eur J Haematol. 2017 Jun;98(6):622-631. doi: 10.1111/ejh.12880. Epub 2017 Apr 17.

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

Author information

1
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
2
Molecular and Cell-Biology Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
3
Department of Hematology and Oncology, Imam Khomeini Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
4
Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

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.

KEYWORDS:

PD-1; Tim-3; chronic lymphocytic leukemia; exhausted T cells

PMID:
28306177
DOI:
10.1111/ejh.12880
[Indexed for MEDLINE]

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