Adaptive NK cell reconstitution is associated with better clinical outcomes

Frank M Cichocki, Emily Taras, Flavia Chiuppesi, John E Wagner, Bruce R Blazar, Claudio G Brunstein, Xianghua Luo, Don J. Diamond, Sarah Cooley, Daniel J. Weisdorf, Jeffrey S Miller

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND. Human cytomegalovirus (CMV) reactivation is a common occurrence early after transplant and is associated with heterogeneous NK cell subset expansion. These adaptive NK cell expansions are highly variable between recipients, with respect to magnitude and relative frequencies of adaptive NK cell subsets. METHODS. To gain insight into the factors that influence adaptive NK cell expansion from a CMV naive graft source, we performed a high-resolution NK cell and CD8+ T cell phenotypic analysis of 215 patients with hematological malignancies that were transplanted with 2 partially HLA matched CMV negative umbilical cord blood units. RESULTS. We found that adaptive NK cells were significantly higher in recipients who received nonmyeloablative conditioning (NMAC) relative to myeloablative conditioning (MAC), and high CMV neutralizing antibody titers correlated with the degree of adaptive NK cell expansion. The frequencies of adaptive NK cell subsets (defined by NKG2C, FcεRγ, EAT-2, and SYK expression) that reconstitute from donor hematopoietic progenitor cells largely matched the frequencies observed in the NK cell compartment of the recipient prior to conditioning, suggesting that host — as well as viral reactivation factors — may determine the phenotypic diversification after transplant. Additionally, multivariable analyses show that higher adaptive NK cell expansion associated with better disease-free survival. CONCLUSIONS. Our findings provide important insights into adaptive NK cell reconstitution after transplant and support a role for adaptive NK cells in promoting better clinical outcomes.

Original languageEnglish (US)
Article numberY
JournalJCI Insight
Volume4
Issue number2
DOIs
StatePublished - Jan 24 2019

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Natural Killer Cells
Cytomegalovirus
Transplants
Hematologic Neoplasms
Hematopoietic Stem Cells
Neutralizing Antibodies
Fetal Blood
Disease-Free Survival
Tissue Donors
T-Lymphocytes

PubMed: MeSH publication types

  • Journal Article

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Adaptive NK cell reconstitution is associated with better clinical outcomes. / Cichocki, Frank M; Taras, Emily; Chiuppesi, Flavia; Wagner, John E; Blazar, Bruce R; Brunstein, Claudio G; Luo, Xianghua; Diamond, Don J.; Cooley, Sarah; Weisdorf, Daniel J.; Miller, Jeffrey S.

In: JCI Insight, Vol. 4, No. 2, Y, 24.01.2019.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND. Human cytomegalovirus (CMV) reactivation is a common occurrence early after transplant and is associated with heterogeneous NK cell subset expansion. These adaptive NK cell expansions are highly variable between recipients, with respect to magnitude and relative frequencies of adaptive NK cell subsets. METHODS. To gain insight into the factors that influence adaptive NK cell expansion from a CMV naive graft source, we performed a high-resolution NK cell and CD8+ T cell phenotypic analysis of 215 patients with hematological malignancies that were transplanted with 2 partially HLA matched CMV negative umbilical cord blood units. RESULTS. We found that adaptive NK cells were significantly higher in recipients who received nonmyeloablative conditioning (NMAC) relative to myeloablative conditioning (MAC), and high CMV neutralizing antibody titers correlated with the degree of adaptive NK cell expansion. The frequencies of adaptive NK cell subsets (defined by NKG2C, FcεRγ, EAT-2, and SYK expression) that reconstitute from donor hematopoietic progenitor cells largely matched the frequencies observed in the NK cell compartment of the recipient prior to conditioning, suggesting that host — as well as viral reactivation factors — may determine the phenotypic diversification after transplant. Additionally, multivariable analyses show that higher adaptive NK cell expansion associated with better disease-free survival. CONCLUSIONS. Our findings provide important insights into adaptive NK cell reconstitution after transplant and support a role for adaptive NK cells in promoting better clinical outcomes.",
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AU - Chiuppesi, Flavia

AU - Wagner, John E

AU - Blazar, Bruce R

AU - Brunstein, Claudio G

AU - Luo, Xianghua

AU - Diamond, Don J.

AU - Cooley, Sarah

AU - Weisdorf, Daniel J.

AU - Miller, Jeffrey S

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