In vivo expansion of a CD9+ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation

Orrantia, Ane; Luis, Enrique Vázquez-De; Astarloa-Pando, Gabirel; Terrén, Íñigo; Amarilla-Irusta, Ainhoa; Polanco-Alonso, Diego; González, Carmen; Uranga, Alasne; Carrascosa, Tomás; Mateos-Mazón, Juan J.; García‐Ruiz, Juan Carlos; Callejas, Sergio; Quintas, Ana; Dopazo, Ana; Zenarruzabeitia, Olatz; Borrego, Francisco

doi:10.1016/j.isci.2022.105235

Cited by 2 publications

(12 citation statements)

References 63 publications

(108 reference statements)

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“…Next, we analyzed the expression of decidual NK cell markers in the pediatric cohort during immune reconstitution, since we have previously discovered that genes codifying CD9 and CD151, two receptors associated with decidual NK cells 55,56 , were overexpressed in adult MM patients after autoHSCT 26 . We observed a temporary increase in both CD9 and CD151 expressing NK cells at S2, decreasing to pre-transplant levels at S5 (Figure 4A).…”

Section: Resultsmentioning

confidence: 99%

“…Another MM study showed a similar redistribution of NK cell populations characterized by a high proliferative rate and an increase in the frequency of both CD56 bright NK cells as well as the most immature population within the CD56 dim NK subset (CD57-NKG2A+) 25 . In general, NK cell function recovers early after autoHSCT 24,25 and transcriptomic analyses have revealed profound changes related, among others, to cell cycle, DNA replication and the mevalonate pathway 26 . Interestingly, following autoHSCT in MM patients there is an expansion of a CD9+ decidual-like NK cell subset that is characterized by high granzyme B and perforin expression levels 26 .…”

Section: Introductionmentioning

confidence: 99%

“…In general, NK cell function recovers early after autoHSCT 24,25 and transcriptomic analyses have revealed profound changes related, among others, to cell cycle, DNA replication and the mevalonate pathway 26 . Interestingly, following autoHSCT in MM patients there is an expansion of a CD9+ decidual-like NK cell subset that is characterized by high granzyme B and perforin expression levels 26 . Nevertheless, the factors responsible for this CD9+ NK cell subset expansion are not known.…”

Section: Introductionmentioning

confidence: 99%

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Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors

Astarloa-Pando,

Polanco-Alonso,

Sandá

et al. 2024

Preprint

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SUMMARYEarly immune reconstitution after autologous hematopoietic stem cell transplantation (autoHSCT) is associated with a better outcome in a variety of cancers. NK cells constitute the first lymphocyte subset to recover in the blood after autoHSCT. We have in-depth characterized them in pediatric patients with different tumors and found that, immediately after autoHSCT, NK cells transiently acquired a decidual-like phenotype, were more immature and activated, and exhibited an increased expression of inhibitory receptors, while activating receptors levels were diminished. This activated and decidual-like phenotype was characterized by increased CD56, CD9, CD49a, CD151, CD38, HLA-DR and CD55 expression. We also determined plasma levels of several cytokines and found that their concentrations were associated with the observed changes in NK cells phenotype.In vitroexperiments, including flow cytometry and single-cell RNA sequencing (scRNA-seq), recapitulated the changes observed in NK cells early after autoHSCT. Specifically, results revealed that the combination of IL-15 and TGF-β induced, at least partially, this distinctive phenotype on NK cells after autoHSCT. Finally, we have observed a positive correlation between relapse and the percentage of CD56dimNK cells shortly after autoHSCT in our cohort of pediatric patients. Altogether, our work is of relevance to understand the physiopathology of NK cells during the immune system reconstitution after autoHSCT in children and potentially help in the management of these patients.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors

Astarloa-Pando,

Polanco-Alonso,

Sandá

et al. 2024

Preprint

Self Cite

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“…NK cells undergo rapid division during leukocyte recovery. Genes related to biological processes such as cell cycle, DNA replication, and energy metabolism, including glycolysis and tricarboxylic acid cycle, were significantly enriched and returned to normal transcript levels after 1 month ( Orrantia et al, 2022 ). Furthermore, during this period, decidual-like NK cells were expanded, characterized by CD9 expression.…”

Section: Involvement Of Nk Cells In the Anti-tumor Response Of Existi...mentioning

confidence: 99%

“…Compared with CD9 − NK cells, they had higher perforin and GZMB levels. However, the significance of the expansion of this subpopulation remains unverified ( Orrantia et al, 2022 ). CD56 low CD16 low NK cells may represent an intermediate stage of differentiation and returns to peak at 2 weeks after transplantation, which is approximately the leukocyte recovery period ( Vulpis et al, 2018 ).…”

Section: Involvement Of Nk Cells In the Anti-tumor Response Of Existi...mentioning

confidence: 99%

Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma

Zhang,

Peng,

et al. 2024

Front. Cell Dev. Biol.

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Multiple myeloma (MM), a stage-developed plasma cell malignancy, evolves from monoclonal gammopathy of undetermined significance (MGUS) or smoldering MM (SMM). Emerging therapies including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, chimeric antigen-T/natural killer (NK) cells, bispecific T-cell engagers, selective inhibitors of nuclear export, and small-molecule targeted therapy have considerably improved patient survival. However, MM remains incurable owing to inevitable drug resistance and post-relapse rapid progression. NK cells with germline-encoded receptors are involved in the natural evolution of MGUS/SMM to active MM. NK cells actively recognize aberrant plasma cells undergoing malignant transformation but are yet to proliferate during the elimination phase, a process that has not been revealed in the immune editing theory. They are potential effector cells that have been neglected in the therapeutic process. Herein, we characterized changes in NK cells regarding disease evolution and elucidated its role in the early clinical monitoring of MM. Additionally, we systematically explored dynamic changes in NK cells from treated patients who are in remission or relapse to explore future combination therapy strategies to overcome drug resistance.

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In vivo expansion of a CD9+ decidual-like NK cell subset following autologous hematopoietic stem cell transplantation

Cited by 2 publications

References 63 publications

Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors

Activated NK cells with a predominance of inhibitory receptors and a decidual-like phenotype expand after autologous HSCT in children with tumors

Natural killer cells affect the natural course, drug resistance, and prognosis of multiple myeloma

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