Cytokine enhancement of immunogenicity in chronic myeloid leukaemia.

Abstract:

:Various clinical and laboratory observations suggest that the leukaemia cells in chronic myeloid leukaemia (CML) are potentially immunogenic. Whilst the ability of the leukaemia cells to elicit an anti-leukaemic immune response in the allogeneic setting is established, it remains unclear why such anti-leukaemic response does not occur in vivo in the autologous setting. We previously demonstrated the presence of leukaemia-reactive T cells in a patient with CML. However, we found that the T cells were normally anergic unless pre-incubated in vitro in high-dose recombinant interleukin-2. We speculated that the T cell anergy was the result of a lack of the appropriate immune costimulatory molecules on the leukaemia cell surface. In this study, we confirm the absence of immune costimulatory molecules, CD80 (B7-1) and CD86 (B7-2), on leukaemia cells and demonstrated that these costimulatory molecules on the leukaemia cells can be upregulated by a combination of GM-CSF and IL-4. There was an associated restoration of leukaemia cell immunogenicity to autologous T cells in mixed lymphocyte leukaemia reactions, suggesting a possible enhancement of anti-leukaemic reaction. More importantly, T cells primed with 'activated' leukaemia cells were able to recognise fresh cytokine-naive leukaemia cells. Furthermore, leukaemia cells expressing the dendritic cell marker, CD1a, were also generated. Our findings therefore suggest the opportunity in future to use these combination cytokines in vivo or these leukaemia cells which have been activated in vitro for leukaemia immunotherapy.

journal_name

Leukemia

journal_title

Leukemia

authors

Coleman S,Throp D,Fisher J,Bailey-Wood R,Lim SH

doi

10.1038/sj.leu.2400858

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

2055-9

issue

12

eissn

0887-6924

issn

1476-5551

journal_volume

11

pub_type

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