Cross-talk among M Cross-talk among M , NK and cancer cells: , NK and cancer cells: M Mcells help NK cells to attack tumor by stimulatory RAE- cells help NK cells to attack tumor by stimulatory RAE- 1 but escape from NK killing by inhibitory Qa-1 1 but escape from NK killing by inhibitory Qa-1 Zhigang Tian, Zhixia Zhou, Cai Zhang ([email protected]) ([email protected]) August 19, 2010, Shenzhen August 19, 2010, Shenzhen Institute of Immunology/School of Life Sciences Institute of Immunology/School of Life Sciences University of Science & Technology of China University of Science & Technology of China Chinese Chinese Academy of Sciences Academy of Sciences Hefei, Anhui, China Hefei, Anhui, China
Cross-talk among M , NK and cancer cells: M cells help NK cells to attack tumor by stimulatory RAE-1 but escape from NK killing by inhibitory Qa-1 Zhigang Tian, Zhixia Zhou, Cai Zhang ([email protected]). Institute of Immunology/School of Life Sciences - PowerPoint PPT Presentation
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Cross-talk among MCross-talk among M, NK and cancer cells:, NK and cancer cells:
MM cells help NK cells to attack tumor by stimulatory RAE-1 but cells help NK cells to attack tumor by stimulatory RAE-1 but escape from NK killing by inhibitory Qa-1escape from NK killing by inhibitory Qa-1
August 19, 2010, ShenzhenAugust 19, 2010, Shenzhen
Institute of Immunology/School of Life SciencesInstitute of Immunology/School of Life SciencesUniversity of Science & Technology of China University of Science & Technology of China
Chinese Academy of SciencesChinese Academy of SciencesHefei, Anhui, ChinaHefei, Anhui, China
Figure 2-49NK cell: a professional killer of tumorNK cell: a professional killer of tumor
Nature review immunology, 2008;8:713
1.initiation 2.effector3.termination
Three main stages of cell lytic synapse
SMAC: supramolecular activation cluster
SMIC: supramolecular inhibitory cluster
Two kinds of immunological synapse
NK Cell Immunological Synapse
NK Cell Immunological SynapseNature review immunology, 2008;8:713
Annu. Rev. Immunol. 2005. 23:225–74
Natural killer cell recognition of “missing self”
KIR : killer immunoglobulin-like receptors
KLR: killer lectin-like receptors
M
NK
Death
Tumor cells
Poly I:C
1. Macrophages increase cytolysis of NK cells against cancer cells
++
% L
ysis
of
NK
cel
ls t
o M
0
1
2
3
4
5
6
50:1 25:1 5:1E/T ratio
Untreated peritoneal Mpoly I:C treated peritoneal M
0102030405060708090
5:1 25:1 50:1
**
% L
ysis
of
NK
cel
ls t
o tu
mor
NK aloneNK/M (medium)NK/M (poly I:C)
*
*
E/T ratio
M
NK
Death
Tumor cells
Poly I:C
NKG2D㈩㈩
2. Poly I:C-treated macrophages increase NKG2D expression of NK cells
Fol
d I
nd
uct
ion
of
N
KG
2D g
ene
0
1
2
3
4
5
6
NK alone NK+
RAW264.7
NK+
RAW264.7(poly I :C)
*
36.48% 32.74% 50.71%
NK onlyNK+
RAW264.7
NK+
RAW264.7 (poly I:C)
NKG2D
Ev e
nts
㈩㈩
M
Death
Tumor cells
Poly I:C
3. Increased NKG2D expression correlates to activation of NK cells
NK onlyNK+
M
NK+
M (poly I:C)
NK+
M (poly I:C)+
Isotype-control
NK+
M (poly I:C)+
anti-NKG2D
Eve
nts
25.71% 25.13% 62.52% 55.03% 38.41%
CD69
NK aloneNK+MØNK+MØ (poly I:C) NK+MØ (poly I:C)+Isotype-contyolNK+MØ (poly I:C)+ anti-NKG2D
0
5
10
15
20
25
*
*
*
Fol
d E
xpre
ssio
n
FasL TRAILPerforin
NK
NKG2D㈩㈩
㈩㈩
M
NK
Death
Tumor cells
Poly I:C
NKG2D㈩㈩
4. Increased NKG2D expression correlates to function of NK cells
MM cells help NK cells to cells help NK cells to attack tumor by RAE-1 but attack tumor by RAE-1 but escape from NK killing by escape from NK killing by
Qa-1Qa-1
Conclusion
Macrophages may activate NK cells to attack tumor by activating RAE-l-NKG2D recognition but protect themselves from cytolysis of NK cells via preferential inhibitory Qa-1-NKG2A recognition, by which the NK cells will constitutively be activated by macrophages to keep strong innate immunity against tumor.
Cross-talk among MCross-talk among M, NK and cancer cells, NK and cancer cells
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20NK receptor complex-ligand interactions
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Klas Kärre
in the laboratory at the Karolinska Institute in 1983.