<i>KIR3DL1</i>/<i>HL</i><i>A-B</i> Subtypes Govern Acute Myelogenous Leukemia Relapse After Hematopoietic Cell Transplantation
-
- Jeanette E. Boudreau
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Fabio Giglio
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Ted A. Gooley
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Philip A. Stevenson
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Jean-Benoît Le Luduec
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Brian C. Shaffer
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Raja Rajalingam
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Lihua Hou
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Carolyn Katovich Hurley
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Harriet Noreen
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Elaine F. Reed
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Neng Yu
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Cynthia Vierra-Green
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Michael Haagenson
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Mari Malkki
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Effie W. Petersdorf
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Stephen Spellman
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
-
- Katharine C. Hsu
- Jeanette E. Boudreau, Fabio Giglio, Jean-Benoît Le Luduec, Brian C. Shaffer, and Katharine C. Hsu, Memorial Sloan Kettering Cancer Center; Brian C. Shaffer and Katharine C. Hsu, Weill Cornell Medical College, New York, NY; Ted A. Gooley, Philip A. Stevenson, Mari Malkki, and Effie W. Petersdorf, Fred Hutchinson Cancer Research Center, Seattle, WA; Raja Rajalingam, University of California, San Francisco, San Francisco; Elaine F. Reed, University of California, Los Angeles, Los Angeles, CA; Lihua Hou and...
Description
<jats:sec><jats:title>Purpose</jats:title><jats:p> Disease relapse remains a major challenge to successful outcomes in patients who undergo allogeneic hematopoietic cell transplantation (HCT). Donor natural killer (NK) cell alloreactivity in HCT can control leukemic relapse, but capturing alloreactivity in HLA-matched HCT has been elusive. HLA expression on leukemia cells—upregulated in the post-HCT environment—signals for NK cell inhibition via inhibitory killer immunoglobulin-like (KIR) receptors and interrupts their antitumor activity. We hypothesized that varied strengths of inhibition among subtypes of the ubiquitous KIR3DL1 and its cognate ligand, HLA-B, would titrate NK reactivity against acute myelogenous leukemia (AML). </jats:p></jats:sec><jats:sec><jats:title>Patients and Methods</jats:title><jats:p> By using an algorithm that was based on polymorphism-driven expression levels and specificities, we predicted and tested inhibitory and cytotoxic NK potential on the basis of KIR3DL1/HLA-B subtype combinations in vitro and evaluated their impact in 1,328 patients with AML who underwent HCT from 9/10 or 10/10 HLA-matched unrelated donors. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> Segregated by KIR3DL1 subtype, NK cells demonstrated reproducible patterns of strong, weak, or noninhibition by target cells with defined HLA-B subtypes, which translated into discrete cytotoxic hierarchies against AML. In patients, KIR3DL1 and HLA-B subtype combinations that were predictive of weak inhibition or noninhibition were associated with significantly lower relapse (hazard ratio [HR], 0.72; P = .004) and overall mortality (HR, 0.84; P = .030) compared with strong inhibition combinations. The greatest effects were evident in the high-risk group of patients with all KIR ligands (relapse: HR, 0.54; P < .001; and mortality: HR, 0.74; P < .008). Beneficial effects of weak and noninhibiting KIR3DL1 and HLA-B subtype combinations were separate from and additive to the benefit of donor activating KIR2DS1. </jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p> Consideration of KIR3DL1-mediated inhibition in donor selection for HLA-matched HCT may achieve superior graft versus leukemia effects, lower risk for relapse, and an increase in survival among patients with AML. </jats:p></jats:sec>
Journal
-
- Journal of Clinical Oncology
-
Journal of Clinical Oncology 35 (20), 2268-2278, 2017-07-10
American Society of Clinical Oncology (ASCO)
- Tweet
Details 詳細情報について
-
- CRID
- 1361418520159660416
-
- ISSN
- 15277755
- 0732183X
-
- Data Source
-
- Crossref