Abstract
Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ + T cells-both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6-to 8-week interval required for the generation of alloreactive NK cells from HSC.
| Original language | English |
|---|---|
| Pages (from-to) | 253-264 |
| Number of pages | 12 |
| Journal | International Archives of Allergy and Immunology |
| Volume | 164 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Nov 7 2014 |
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Keywords
- Activating NK receptors
- Haploidentical hematopoietic stem cell transplantation
- Killer Ig-like receptors
- Natural killer cells
- NK-tumor cell interactions
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
- Medicine(all)
Cite this
Human natural killer cells : Origin, receptors, function, and clinical applications. / Moretta, Lorenzo; Montaldo, Elisa; Vacca, Paola; Del Zotto, Genny; Moretta, Francesca; Merli, Pietro; Locatelli, Franco; Mingari, Maria Cristina.
In: International Archives of Allergy and Immunology, Vol. 164, No. 4, 07.11.2014, p. 253-264.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human natural killer cells
T2 - Origin, receptors, function, and clinical applications
AU - Moretta, Lorenzo
AU - Montaldo, Elisa
AU - Vacca, Paola
AU - Del Zotto, Genny
AU - Moretta, Francesca
AU - Merli, Pietro
AU - Locatelli, Franco
AU - Mingari, Maria Cristina
PY - 2014/11/7
Y1 - 2014/11/7
N2 - Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ + T cells-both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6-to 8-week interval required for the generation of alloreactive NK cells from HSC.
AB - Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ + T cells-both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6-to 8-week interval required for the generation of alloreactive NK cells from HSC.
KW - Activating NK receptors
KW - Haploidentical hematopoietic stem cell transplantation
KW - Killer Ig-like receptors
KW - Natural killer cells
KW - NK-tumor cell interactions
UR - http://www.scopus.com/inward/record.url?scp=84908566276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84908566276&partnerID=8YFLogxK
U2 - 10.1159/000365632
DO - 10.1159/000365632
M3 - Article
C2 - 25323661
AN - SCOPUS:84908566276
VL - 164
SP - 253
EP - 264
JO - International Archives of Allergy and Immunology
JF - International Archives of Allergy and Immunology
SN - 1018-2438
IS - 4
ER -