TY - JOUR
T1 - A novel immature natural killer cell subpopulation predicts relapse after cord blood transplantation
AU - Li, Li
AU - Chen, Han
AU - Marin, David
AU - Xi, Yuanxin
AU - Miao, Qi
AU - Lv, Jiangxing
AU - Banerjee, Pinaki Prosad
AU - Shaim, Hila
AU - Daher, May
AU - Basar, Rafet
AU - Imahashi, Nobuhiko
AU - Jimenez, Juan
AU - Hu, Bingqian
AU - Mehta, Rohtesh S.
AU - Kerbauy, Lucila Nassif
AU - Kaplan, Mecit
AU - Mendt, Mayela
AU - Ozcan, Gonca
AU - Gokdemir, Elif
AU - Sanabria, Mayra Hernandez
AU - Li, Ye
AU - Chen, Ken
AU - Wang, Jing
AU - Muniz-Feliciano, Luis
AU - Zhao, Wei Li
AU - Champlin, Richard E.
AU - Shpall, Elizabeth J.
AU - Rezvani, Katayoun
N1 - Funding Information:
This work was supported by National Institutes of Health, National Cancer Institute grants (CA061508-21A1 and CA211044-01), the Cancer Prevention and Research Institute of Texas (RP160693), and the MD Anderson Cancer Center Institutional Research Grant Program. The Flow Cytometry and Cellular Imaging Facility is supported in part by the National Institutes of Health, National Cancer Institute through a support grant to MD Anderson Cancer Center (CA016672).
Publisher Copyright:
© 2019 by The American Society of Hematology.
PY - 2019/12/10
Y1 - 2019/12/10
N2 - Natural killer (NK) cells are highly heterogeneous, with vast phenotypic and functional diversity at the single-cell level. They are involved in the innate immune response against malignant and virus-infected cells. To understand the effect of NK diversity during immune recovery on the antitumor response after cord blood transplantation (CBT), we used high-dimensional mass cytometry and the metrics of NK cell diversity to study the NK cell repertoire in serial samples from 43 CBT recipients. A higher-diversity index based on single-cell combinatorial phenotypes was significantly associated with a lower risk for relapse after CBT (P 5 .005). Cytomegalovirus reactivation was a major factor in the development of a more diverse NK repertoire after CBT. Notably, we identified a group of patients whose CB-derived NK cells after transplantation possessed an immature phenotype (CB-NKim), characterized by poor effector function and a low diversity index. Frequencies of CB-NKim of 11.8% or higher during the early post-CBT recovery phase were highly predictive for relapse (area under the curve [AUC], 0.979), a finding that was validated in a second independent cohort of patients (n 5 25; AUC, 0.977). Moreover, we showed that the maturation, diversity, and acquisition of effector function by CB-NKim early after CBT were driven by interleukin 15. Our data indicate that the diversity of the NK cell repertoire after CBT contributes importantly to the risk for subsequent relapse. We suggest that the use of diversity metrics and high-dimensional mass cytometry may be useful tools in predicting clinical outcomes and informing the design of therapeutic strategies to prevent relapse after CBT.
AB - Natural killer (NK) cells are highly heterogeneous, with vast phenotypic and functional diversity at the single-cell level. They are involved in the innate immune response against malignant and virus-infected cells. To understand the effect of NK diversity during immune recovery on the antitumor response after cord blood transplantation (CBT), we used high-dimensional mass cytometry and the metrics of NK cell diversity to study the NK cell repertoire in serial samples from 43 CBT recipients. A higher-diversity index based on single-cell combinatorial phenotypes was significantly associated with a lower risk for relapse after CBT (P 5 .005). Cytomegalovirus reactivation was a major factor in the development of a more diverse NK repertoire after CBT. Notably, we identified a group of patients whose CB-derived NK cells after transplantation possessed an immature phenotype (CB-NKim), characterized by poor effector function and a low diversity index. Frequencies of CB-NKim of 11.8% or higher during the early post-CBT recovery phase were highly predictive for relapse (area under the curve [AUC], 0.979), a finding that was validated in a second independent cohort of patients (n 5 25; AUC, 0.977). Moreover, we showed that the maturation, diversity, and acquisition of effector function by CB-NKim early after CBT were driven by interleukin 15. Our data indicate that the diversity of the NK cell repertoire after CBT contributes importantly to the risk for subsequent relapse. We suggest that the use of diversity metrics and high-dimensional mass cytometry may be useful tools in predicting clinical outcomes and informing the design of therapeutic strategies to prevent relapse after CBT.
UR - http://www.scopus.com/inward/record.url?scp=85083377923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083377923&partnerID=8YFLogxK
U2 - 10.1182/BLOODADVANCES.2019000835
DO - 10.1182/BLOODADVANCES.2019000835
M3 - Article
C2 - 31821460
AN - SCOPUS:85083377923
SN - 2473-9529
VL - 3
SP - 4117
EP - 4130
JO - Blood Advances
JF - Blood Advances
IS - 23
ER -