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In vivo tumor cell rejection induced by NK cell inhibitory receptor blockade: maintained tolerance to normal cells even in the presence of IL-2.

Abstract：

:Missing-self-reactivity can be mimicked by blocking self-specific inhibitory receptors on NK cells, leading to increased rejection of syngeneic tumor cells. Using a mouse model, we investigated whether Ab-mediated blocking of inhibitory receptors, to a degree where NK cells rejected syngeneic tumor cells, would still allow self-tolerance toward normal syngeneic cells. Ly49C/I inhibitory receptors on C57BL/6 (H-2(b)) NK cells were blocked with F(ab')(2) fragments of the mAb 5E6. Inhibitory receptor blockade in vivo caused rejection of i.v. inoculated fluorescence-labeled syngeneic lymphoma line cells but not of syngeneic spleen cells, BM cells or lymphoblasts. The selective rejection of tumor cells was NK cell-dependent and specifically induced by Ly49C/I blockade. Moreover, selective tumor rejection was maintained after treatment with 5E6 F(ab')(2) for 9 wk, arguing against the induction of NK cell anergy or autoreactivity during this time. Combination therapy using 5E6 F(ab')(2) together with high dose IL-2 treatment further increased lymphoma cell rejection. In addition, combination therapy reduced growth of melanoma cell line tumors established by s.c. inoculation 3 days before start of treatment. Our results demonstrate that inhibitory receptor blockade does not result in attack on normal cells, despite potent reactivity against MHC class I-expressing tumors.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Vahlne G,Lindholm K,Meier A,Wickström S,Lakshmikanth T,Brennan F,Wilken M,Nielsen R,Romagné F,Wagtmann NR,Kärre K,Johansson MH

doi

10.1002/eji.200939755

subject

Has Abstract

pub_date

2010-03-01 00:00:00

pages

813-23

issue

3

eissn

0014-2980

issn

1521-4141

journal_volume

40

pub_type

杂志文章

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