Characterization of the recognition and functional heterogeneity exhibited by cytokine‐induced killer cell subsets against acute myeloid leukaemia target cell

Abstract

Summary The polyclonal cytokine‐induced killer (CIK) cells exhibit potent cytotoxicity against a variety of tumour cells including autologous and allogeneic acute myeloid leukaemic (AML) targets. At maturity, three lymphocyte subsets: CD3− CD56+, CD3+ CD56− and CD3+ CD56+, constitute the bulk of the CIK cell culture. The CD3− CD56+ subset behaves like classical natural killer (NK) cells where cytotoxicity is potentiated by blocking the human leucocyte antigen Class I molecules in the AML targets. Both the CD3+ CD56+ and CD3+ CD56− subsets, though known to kill autologous and allogeneic targets to a comparable degree and therefore non‐major histocompatibility complex (MHC)‐restricted, nevertheless require the presence of the MHC molecule on the target, which interacts with their CD3–T‐cell receptor complex. Although CIK cells are often termed ‘NK‐like’ T cells, we have demonstrated that the well‐characterized NK receptors KIR, NKG2C/E, NKG2D and DNAM‐1 are not involved in the process of AML recognition for the CD3+ CD56− and CD3+ CD56+ subsets. The CD3+ CD56+ and CD3+ CD56− subsets express a polyclonal and comparable TCRVβ repertoire in a Gaussian distribution. The CD3+ CD56+ subset kills AML targets more efficiently than its CD3+ CD56− counterpart because of the presence of a higher proportion of CD8+ cells. The CD3+ CD56+ subset comprise more terminally differentiated late effector T cells that bear the CD27+ CD28− or CD27− CD28− phenotype, with a higher granzyme A content. In comparison, the phenotype of the CD3+ CD56− subset is consistent with early effector T cells that are CD27+ CD28+ and CD62L+, known to be less cytotoxic but possess greater proliferative potential.

The anti-tumour activity of allogeneic cytokine-induced killer cells in patients who relapse after allogeneic transplant for haematological malignancies

“…The small NK subset within the bulk CIK culture complements T cells in the killing of targets that may escape T-cell surveillance by downregulation of Class I Ag. 36 By complement-and Ab-dependent cytotoxicity mediated by NK subset within CIK culture, it was recently shown that combination with anti-CD20 Ab further enhanced their anti-lymphoma activity. 37 Other strategies include timing of infusion to coincide with nadir of lymphopenia for maximal homoeostatic expansion of adoptively transferred T cells.…”

Cytokine-Induced NK-Like T Cells: From Bench to Bedside

“…The sorted NK cell fraction (CD3 − CD56 + ) behaves like classical NK cells and the killing of autologous acute myeloid leukemia (AML) target cells mediated by these cells can be enhanced by blocking the HLA class I molecules on the target cells [12]. The CD3 + CD56 + subset, termed non-MHC-restricted T cells, is able to kill both autologous and allogeneic susceptible tumor targets such as primary AML cells of disparate HLA types [11].…”

Natural killer-like T CD3+/CD16+CD56+ cells in chronic lymphocytic leukemia: Intracellular cytokine expression and relationship with clinical outcome

“…These CD3 + CD56 + cells have been termed cytokine-induced killer cells (CIK cells) and it was shown that they possess enhanced cytotoxicity against various tumor cells (23). In contrast to NK-like T cells that are de novo, CIK cells are generated following in vitro culturing (24,25 (27,28). To our knowledge, this is the first study of this cell population investigating the relationship between the peripheral blood CD3 + /CD16 + CD56 + cells and clinical outcome in newly diagnosed patients with CLL.…”