Loss or down‐regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts

Masuda, Kozo; Hiraki, Akio; Fujii, Nobuharu; Watanabe, Toshiyuki; Tanaka, Motoyuki; Matsue, Kosei; Ogama, Yoichiro; Ouchida, Mamoru; Shimizu, Kenji; Ikeda, Kazuma; Tanimoto, Mitsune

doi:10.1111/j.1349-7006.2006.00356.x

Cited by 55 publications

(57 citation statements)

References 42 publications

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“…The pool of the CCRF-CEM HSPA eluted peptides shown in Table 1 was subjected to HLA class I epitope database searches with the restrictions to the HLA alleles of the cell line. The leukemic cell line, CCRF-CEM, has been reported to express HLA class I alleles, including A*0101, 31012; B*0801, 4001 and C*0304, 0701 (Adams et al 2005;Masuda et al 2007). As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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Heat shock protein 70 (HSPA) is a molecular chaperone which has been suggested to shuttle human leukocyte antigen (HLA) epitope precursors from the proteasome to the transporter associated with antigen processing. Despite the reported observations that peptides chaperoned by HSPA are an effective source of antigens for cross-priming, little is known about the peptides involved in the process. In this study, we investigated the possible involvement of HSPA in HLA class I or class II antigen presentation and analysed the antigenic potential of the associated peptides. HSPA was purified from CCRF-CEM and K562 cell lines, and using mass spectrometry techniques, we identified 44 different peptides which were copurified with HSPA. The affinity of the identified peptides to two HSPA isoforms, HSPA1A and HSPA8, was confirmed using a peptide array. Four of the HSPAassociated peptides were matched with 13 previously reported HLA epitopes. Of these 13 peptides, nine were HLA class I and four were HLA class II epitopes. These results demonstrate the association of HSPA with HLA class I and class II epitopes, therefore providing further evidence for the involvement of HSPA in the antigen presentation process.

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Section: Resultsmentioning

confidence: 99%

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Stocki

Morris

Preisinger

et al. 2010

Cell Stress and Chaperones

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“…Although some studies suggested that the expression of HLA class I is low in myeloid malignancies (49), this was relative to the much higher levels on lymphoid cells (autologous T cells). In fact, other studies reported relatively intact levels of HLA class I in acute leukemia (50,51). Experimentally, NK cells expanding in response to CMV have a heightened cytolytic potential, but only against mismatched blasts, because they are efficiently inhibited by cognate HLA class I molecules (L.L.…”

Section: Discussionmentioning

confidence: 99%

Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

Björklund

Clancy

Goodridge

et al. 2016

The Journal of Immunology

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Acute and latent human CMV cause profound changes in the NK cell repertoire, with expansion and differentiation of educated NK cells expressing self-specific inhibitory killer cell Ig-like receptors. In this study, we addressed whether such CMV-induced imprints on the donor NK cell repertoire influenced the outcome of allogeneic stem cell transplantation. Hierarchical clustering of high-resolution immunophenotyping data covering key NK cell parameters, including frequencies of CD56bright, NKG2A+, NKG2C+, and CD57+ NK cell subsets, as well as the size of the educated NK cell subset, was linked to clinical outcomes. Clusters defining naive (NKG2A+CD57−NKG2C−) NK cell repertoires in the donor were associated with decreased risk for relapse in recipients with acute myeloid leukemia and myelodysplastic syndrome (hazard ratio [HR], 0.09; 95% confidence interval [CI]: 0.03–0.27; p < 0.001). Furthermore, recipients with naive repertoires at 9–12 mo after hematopoietic stem cell transplantation had increased disease-free survival (HR, 7.2; 95% CI: 1.6–33; p = 0.01) and increased overall survival (HR, 9.3; 95% CI: 1.1–77, p = 0.04). Conversely, patients with a relative increase in differentiated NK cells at 9–12 mo displayed a higher rate of late relapses (HR, 8.41; 95% CI: 6.7–11; p = 0.02), reduced disease-free survival (HR, 0.12; 95% CI: 0.12–0.74; p = 0.02), and reduced overall survival (HR, 0.07; 95% CI: 0.01–0.69; p = 0.02). Thus, our data suggest that naive donor NK cell repertoires are associated with protection against leukemia relapse after allogeneic HSCT.

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“…Most types of solid tumors display defects in HLA class I expression, but the incidence of HLA class I downregulation and complete HLA class I allele loss varies among different types of tumors. 15 In contrast to solid tumors, HLA class I expression in leukemia has not been extensively studied, except in acute leukemia [16][17][18][19][20] and B-CLL. 21 In most of these studies, complete loss of HLA class I allele(s) in leukemic cells was infrequent.…”

Section: Cell Surface Expression Of Hla Class I Moleculesmentioning

confidence: 99%

NK cell receptors and their ligands in leukemia

Verheyden

Demanet

2007

Leukemia

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Human natural killer (NK) cells are built to kill abnormal cells but to preserve autologous normal cells. To accomplish this task, they are equipped with a large number of inhibiting and activating receptors. Ligation with corresponding ligands will determine whether the NK cell becomes activated to destroy the abnormal cell. This review will focus on the abnormalities of NK cell receptors and their putative ligands found in patients with leukemia, which can lead to an inadequate function of NK cells allowing these malignant cells to escape from NK cell destruction. In recent years it has become clear that NK cells in the haploidentical hematopoietic stem cell transplantation (HSCT) setting are very effective in eliminating residual acute myeloid, but not acute lymphoid, leukemic cells. In this regard, we also reviewed published studies of retrospective cohorts of HSCT investigating the potential beneficial effect of killer-cell immunoglobulin-like receptors (KIRs) and human leukocyte antigen (HLA) ligands on NK alloreactivity. Manipulating NK cell inhibition or activation could lead to new forms of immunotherapy, ultimately leading to the elimination of resistant leukemic cells.

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Loss or down‐regulation of HLA class I expression at the allelic level in freshly isolated leukemic blasts

Cited by 55 publications

References 42 publications

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Identification of potential HLA class I and class II epitope precursors associated with heat shock protein 70 (HSPA)

Naive Donor NK Cell Repertoires Associated with Less Leukemia Relapse after Allogeneic Hematopoietic Stem Cell Transplantation

NK cell receptors and their ligands in leukemia

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