Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack?

Demanet, Christian; Mulder, Arend; Deneys, Véronique; Worsham, Maria J.; Maes, Piet; Claas, Frans H.J.; Ferrone, Soldano

doi:10.1182/blood-2003-07-2500

Cited by 97 publications

(78 citation statements)

References 27 publications

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“…Our previous study showed that the HLA class I expression on most leukemic cells was downregulated, but was mostly restricted to HLA-A and HLA-B belonging to the Bw6 group. 6 As Bw4, but not Bw6, protects target cells from NK cell attack, the inhibitory interaction mediated by KIR3DL1 and Bw4 in CLL described in this study is in agreement with our previous observation. 6 Next, we investigated the frequencies of these KIR genes in combination with their HLA class I ligands in patients with myeloid leukemia.…”

supporting

confidence: 93%

“…6 As Bw4, but not Bw6, protects target cells from NK cell attack, the inhibitory interaction mediated by KIR3DL1 and Bw4 in CLL described in this study is in agreement with our previous observation. 6 Next, we investigated the frequencies of these KIR genes in combination with their HLA class I ligands in patients with myeloid leukemia. We analyzed patients with acute myeloid leukemia (n ¼ 29) and chronic myeloid leukemia (CML) (n ¼ 19) together as one group, because recent clinical studies in HLAmismatched HSCT showed that patients with myeloid leukemia are susceptible to NK cell killing.…”

supporting

confidence: 93%

See 1 more Smart Citation

Susceptibility to myeloid and lymphoid leukemia is mediated by distinct inhibitory KIR-HLA ligand interactions

Verheyden

Demanet

2006

Leukemia

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supporting

confidence: 93%

supporting

confidence: 93%

Susceptibility to myeloid and lymphoid leukemia is mediated by distinct inhibitory KIR-HLA ligand interactions

Verheyden

Demanet

2006

Leukemia

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“…14, 15 The CD94/ NKG2 heterodimers has been shown to recognize the nonclassical HLA-E molecule and depending on the type of NKG2 receptor the generated signal can be inhibiting (NKG2A) or activating (NKG2C and NKG2E). 16 Recently, our 17 and other studies [18][19][20] demonstrated that leukemic cells can have downregulated expression of HLA class I molecule and putative allele loss. [17][18][19][20] Moreover, recent studies support a major role for NK cells in the graft-versusleukemia effect in allogeneic stem cell transplantation.…”

Section: Introductionmentioning

confidence: 87%

“…16 Recently, our 17 and other studies [18][19][20] demonstrated that leukemic cells can have downregulated expression of HLA class I molecule and putative allele loss. [17][18][19][20] Moreover, recent studies support a major role for NK cells in the graft-versusleukemia effect in allogeneic stem cell transplantation. [21][22][23] These data demonstrate that NK cells could play an important role in the innate immune surveillance of leukemic cells.…”

Section: Introductionmentioning

confidence: 87%

Identification of natural killer cell receptor phenotypes associated with leukemia

2004

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Natural killer (NK) cells play a key role in defense against tumor cells that have the capacity to downregulate human leukocyte antigen (HLA) class I expression. It has been reported that leukemic cells can have downregulated expression of HLA class I molecules. The polymorphic nature of NK cell receptor (NKR) genes generates diverse repertoires in the human population, which display specificity in the innate immune response. In the present study, 11 KIR and two CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148 healthy Caucasians. Here, we report a significant increased frequency of the more inhibitory AB killer cell immunoglobulin-like receptor (KIR) phenotype in leukemic patients compared to the controls (31.1% in healthy controls vs 51.0% in leukemic patients, P c ¼ 0.002), which is related to the high prevalence of the inhibitory KIR2DL2 in this population (P c ¼ 0.007). Moreover, two specific KIR phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly associated with leukemic patients. Our study suggests that an important percentage of leukemic patients express a KIR phenotype in favor of escape from NK cell immunity.

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“…Finding a discrepancy between RNA and DNA templates in one sample suggests either select HLA down regulation or a HLA-C nonexpressed allele, which has been reported [27]. This is important and may have functional implications, since one mechanism by which tumor cells evade the immune system is by down regulation of class I HLA [28,29]. This possibility suggests that KIR-ligand determination from RNA may be more functionally accurate.…”

Section: Discussionmentioning

confidence: 86%

A novel method for KIR-ligand typing by pyrosequencing to predict NK cell alloreactivity

Yun¹,

Tolar²,

Yerich³

et al. 2007

Clinical Immunology

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Studies have shown that KIR-ligand mismatching to predict NK cell alloreactivity may result in less relapse and better survival in patients with AML. KIR-ligands are distinguished by single nucleotide polymorphisms (SNPs) from HLA-B and HLA-C sequences. We hypothesized that pyrosequencing to determine KIR-ligand status by direct sequencing of the ligand epitope can be done as an alternative to high resolution HLA-typing. Pyrosequencing is rapid and would be particularly useful in analysis of retrospective cohorts where high resolution HLA-typing is unavailable or too expensive. To validate this assay, RNA and DNA from 70 clinical samples were tested for KIR-ligand by pyrosequencing. Primer binding to invariant regions without known SNPs was critical for KIR-ligand assignment by pyrosequencing to be in full concordance with high resolution HLA-typing. Pyrosequencing is sensitive, specific, high-throughput, inexpensive, and can rapidly screen KIRligand status to evaluate potential alloreactive NK cell or transplant donors.

show abstract

Down-regulation of HLA-A and HLA-Bw6, but not HLA-Bw4, allospecificities in leukemic cells: an escape mechanism from CTL and NK attack?

Cited by 97 publications

References 27 publications

Susceptibility to myeloid and lymphoid leukemia is mediated by distinct inhibitory KIR-HLA ligand interactions

Susceptibility to myeloid and lymphoid leukemia is mediated by distinct inhibitory KIR-HLA ligand interactions

Identification of natural killer cell receptor phenotypes associated with leukemia

A novel method for KIR-ligand typing by pyrosequencing to predict NK cell alloreactivity

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