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. 2017 Jun 12:8:675.
doi: 10.3389/fimmu.2017.00675. eCollection 2017.

"VSports最新版本" HLA-Bw4-I-80 Isoform Differentially Influences Clinical Outcome As Compared to HLA-Bw4-T-80 and HLA-A-Bw4 Isoforms in Rituximab or Dinutuximab-Based Cancer Immunotherapy

Amy K Erbe  1 , Wei Wang  1 , Patrick K Reville  1 , Lakeesha Carmichael  2 , KyungMann Kim  2 , Eneida A Mendonca  2 , Yiqiang Song  2 , Jacquelyn A Hank  1 , Wendy B London  3 , Arlene Naranjo  4 , Fangxin Hong  5 , Michael D Hogarty  6 , John M Maris  7 , Julie R Park  8   9 , M F Ozkaynak  10 , Jeffrey S Miller  11 , Andrew L Gilman  12 , Brad Kahl  13 , Alice L Yu  14   15 , Paul M Sondel  1   16
Affiliations

HLA-Bw4-I-80 Isoform Differentially Influences Clinical Outcome As Compared to HLA-Bw4-T-80 and HLA-A-Bw4 Isoforms in Rituximab or Dinutuximab-Based Cancer Immunotherapy

Amy K Erbe (VSports) et al. Front Immunol. .

Abstract (VSports手机版)

Killer-cell immunoglobulin-like receptors (KIRs) are a family of glycoproteins expressed primarily on natural killer cells that can regulate their function. Inhibitory KIRs recognize MHC class I molecules (KIR-ligands) as ligands. We have reported associations of KIRs and KIR-ligands for patients in two monoclonal antibody (mAb)-based trials: (1) A Children's Oncology Group (COG) trial for children with high-risk neuroblastoma randomized to immunotherapy treatment with dinutuximab (anti-GD2 mAb) + GM-CSF + IL-2 + isotretinion or to treatment with isotretinoin alone and (2) An Eastern Cooperative Oncology Group (ECOG) trial for adults with low-tumor burden follicular lymphoma responding to an induction course of rituximab (anti-CD20 mAb) and randomized to treatment with maintenance rituximab or no-maintenance rituximab. In each trial, certain KIR/KIR-ligand genotypes were associated with clinical benefit for patients randomized to immunotherapy treatment (immunotherapy in COG; maintenance rituximab in ECOG) as compared to patients that did not receive the immunotherapy [isotretinoin alone (COG); no-maintenance (ECOG)]. Namely, patients with both KIR3DL1 and its HLA-Bw4 ligand (KIR3DL1+/HLA-Bw4+ genotype) had improved clinical outcomes if randomized to immunotherapy regimens, as compared to patients with the KIR3DL1+/HLA-Bw4+ genotype randomized to the non-immunotherapy regimen. Conversely, patients that did not have the KIR3DL1+/HLA-Bw4+ genotype showed no evidence of a difference in outcome if receiving the immunotherapy vs VSports手机版. no-immunotherapy. For each trial, HLA-Bw4 status was determined by assessing the genotypes of three separate isoforms of HLA-Bw4: (1) HLA-B-Bw4 with threonine at amino acid 80 (B-Bw4-T80); (2) HLA-B-Bw4 with isoleucine at amino acid 80 (HLA-B-Bw4-I80); and (3) HLA-A with a Bw4 epitope (HLA-A-Bw4). Here, we report on associations with clinical outcome for patients with KIR3DL1 and these separate isoforms of HLA-Bw4. Patients randomized to immunotherapy with KIR3DL1+/A-Bw4+ or with KIR3DL1+/B-Bw4-T80+ had better outcome vs. those randomized to no-immunotherapy, whereas for those with KIR3DL1+/B-Bw4-I80+ there was no evidence of a difference based on immunotherapy vs. no-immunotherapy. Additionally, we observed differences within treatment types (either within immunotherapy or no-immunotherapy) that were associated with the genotype status for the different KIR3DL1/HLA-Bw4-isoforms. These studies suggest that specific HLA-Bw4 isoforms may differentially influence response to these mAb-based immunotherapy, further confirming the involvement of KIR-bearing cells in tumor-reactive mAb-based cancer immunotherapy. .

Keywords: HLA; HLA-Bw4; KIR; KIR-ligand; MHC class I; cancer immunotherapy; natural killer cells. V体育安卓版.

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Figures

Figure 1
Figure 1
KIR3DL1/HLA-Bw4 isoforms differentially influence event-free survival (EFS) in neuroblastoma patients. In neuroblastoma patients treated with immunotherapy (black lines) or isotretinoin alone (red lines), genotype statuses of KIR3DL1/A-Bw4 (A), KIR3DL1/B-Bw4-T80 (B), and KIR3DL1/B-Bw4-I80 (C) had differential effects on EFS. Those with the genes present are represented by solid lines, and those without the genes present are represented by dotted lines. The number of patients at risk for EFS at a given time point are provided below the x-axis. *p < 0.5 and #p < 0.10.
Figure 2
Figure 2
KIR3DL1/HLA-Bw4 isoforms differentially influence duration of response in follicular lymphoma (FL) patients. In FL patients treated with maintenance rituximab (red lines) or no-maintenance rituximab (black lines), genotype statuses of KIR3DL1/A-Bw4 (A), KIR3DL1/B-Bw4-T80 (B), and KIR3DL1/B-Bw4-I80 (C) had differential effects on duration of response. Those with the genes present are represented by solid lines, and those without the genes present are represented by dotted lines. The number of patients at risk for duration of response at a given time point are provided below the x-axis. **p < 0.01, *p < 0.5, and #p < 0.10.
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