G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

Yc, Su; Li, Shuai Cheng; Ck, Hsu; Cao, Yu; Tj, Lin; Cy, Lee; Liao, Hung-Ju

doi:10.1038/bmt.2011.22

Cited by 30 publications

(24 citation statements)

References 34 publications

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“…Meanwhile, in accordance with a previous report,8, 9 we found that the cytotoxicity of overall NK cells, CD56 bri NK subsets as well as CD56 dim NK subsets in GPB was significantly decreased compared to that in NGPB, which could not be rescued by IL‐2 stimulation. Based on the data in this study, we propose the following hypotheses.…”

Section: Discussionsupporting

confidence: 93%

“…However, the predictive value of KIR ligand mismatch on clinical outcome has been inconsistent among different transplantation centres utilizing different protocols 6, 7. One of the most important reasons would be the in vivo application of G‐CSF for donor stem cell preparation that decreased the cytotoxicity of NK cells 8, 9. However, previous studies have considered only the cytotoxic roles of NK cells under haploidentical transplantation while neglecting the immune regulatory effect of NK cells.…”

Section: Introductionmentioning

confidence: 99%

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Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Han

et al. 2018

J Cellular Molecular Medi

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Granulocyte colony‐stimulating factor (G‐CSF) has been widely used in the field of allogeneic haematopoietic stem cell transplantation (allo‐HSCT) for priming donor stem cells from the bone marrow (BM) to peripheral blood (PB) to collect stem cells more conveniently. Donor‐derived natural killer (NK) cells have important antitumour functions and immune regulatory roles post‐allo‐HSCT. The aim of this study was to evaluate the effect of G‐CSF on donors' NK cells in BM and PB. The percentage of NK cells among nuclear cells and lymphocyte was significantly decreased and led to increased ratio of T and NK cells in BM and PB post‐G‐CSF in vivo application. Relative expansion of CD56bri NK cells led to a decreased ratio of CD56dim and CD56bri NK subsets in BM and PB post‐G‐CSF in vivo application. The expression of CD62L, CD54, CD94, NKP30 and CXCR4 on NK cells was significantly increased in PB after G‐CSF treatment. G‐CSF treatment decreased the IFN‐γ‐secreting NK population (NK1) dramatically in BM and PB, but increased the IL‐13‐secreting NK (NK2), TGF‐β‐secreting NK (NK3) and IL‐10‐secreting NK (NKr) populations significantly in BM. Clinical data demonstrated that higher doses of NK1 infused into the allograft correlated with an increased incidence of chronic graft‐vs‐host disease post‐transplantation. Taken together, our results show that the in vivo application of G‐CSF can modulate NK subpopulations, leading to an increased ratio of T and NK cells and decreased ratio of CD56dim and CD56bri NK cells as well as decreased NK1 populations in both PB and BM.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Han

et al. 2018

J Cellular Molecular Medi

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“…Several studies have demonstrated that G-CSF mobilizes regulatory T and NK cells into the peripheral blood, impairs T and NK TH1-type reactions and produces an immune-suppressive environment. [33][34][35][36][37][38][39] All patients in our cohort received G-CSF post transplant, starting from day +6 till engraftment. Interestingly our results align with those by Le Blanc et al…”

Section: Discussionmentioning

confidence: 99%

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

Gul

Meter

Abidi

et al. 2015

Bone Marrow Transplant

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Multiple reports have shown that low absolute lymphocyte count at day 30 (ALC30) after allogeneic hematopoietic SCT (AHSCT) is associated with higher risk of disease relapse and worse OS. However, these reports included heterogeneous populations with different grafts and GVHD prophylaxis. Therefore, we retrospectively evaluated the association of ALC30 with transplant outcomes in a cohort of 381 consecutive patients who underwent AHSCT between 2005 and 2010 and received T-replete PBSC grafts and Tacrolimus/Mycophenolate combination as GVHD prophylaxis. Median follow-up was 57 months. Lower ALC30 (⩽400 × 10 6 /L) was associated with lower OS and increased nonrelapse mortality (NRM) for the whole cohort as well as for recipients of SD and UD grafts separately. Lower ALC30 was associated with more severe acute GVHD (aGVHD; III-IV) for the entire cohort as well as for the SD and UD groups. No association was found between lower ALC30 and relapse. Pretransplant factors associated with lower ALC30 were: unrelated donors; HLA mismatch; older donors; lower recipient age; and lower CD34+ cell dose. In this large retrospective study, ALC30 ⩽ 400 × 10 6 /L was associated with worse OS, increased NRM and severe aGVHD.

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“…62 No impact 64 DC T-and NK-cell priming, temper T-cell alloreactivity, may impair GVL efficacy Induced IL-4 and IL-10 production 42,44 Increased mobilization of pDC and regulatory mDC compared with G-CSF. 62,63 NK Immune recovery, GVL Impaired cytotoxicity 55 Increased mobilization compared with G-CSF. 62 Reduced mobilization 63 Abbreviations: mDC = monocyte-derived dendritic cells; pDC = plasmacytoid-derived dendritic cells; NK = NK cells; T CD3 + = T lymphocytes; T EM = T effector memory; Th2 = T helper 2 lymphocytes; Treg = regulatory T cells.…”

Section: T Emmentioning

confidence: 99%

“…54 There is evidence of a detrimental effect of G-CSF on their function, which seems to be transient and not to affect late-phase GVL activity. 55 Given the variety of immune cells contained in the apheresis product, many strategies have been developed in order to rationally select graft effectors and provide designed adoptive immunotherapies, especially in the haploidentical stem cell transplant setting. [56][57][58] In this scenario, Schumm et al 59 recently introduced an innovative approach of graft manipulation, which consist in depleting the leukapheresis product of only TCR αβ + T cells and CD19 + B cells, thus retaining large numbers of crucial immune effectors such as TCR γδ + T cells, NK cells and DCs; this method has been safely tested in a cohort of children by Locatelli and colleagues.…”

Section: Mobilized Pbsc: the Immunological Perspective F Saraceni Et Almentioning

confidence: 99%

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

Saraceni

Shem‐Tov

Olivieri

et al. 2015

Bone Marrow Transplant

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Although stem cell mobilization has been performed for more than 20 years, little is known about the effects of mobilizing agents on apheresis composition and the impact of graft cell subsets on patients' outcome. With the increasing use of plerixafor and the inclusion of poor mobilizers in autologous transplant procedures, new parameters other than CD34 + stem cell dose are emerging; plerixafor seems to mobilize more primitive CD34 + /CD38 − stem cells compared with G-CSF, but their correlation with stable hematopoietic engraftment is still obscure. Immune recovery is as crucial as hematopoietic reconstitution, and higher T and natural killer cells infused within the graft have been correlated with better outcome in autologous transplant; recent studies showed increased mobilization of immune effectors with plerixafor compared with G-CSF, but further data are needed to clarify the clinical impact of these findings. In the allogeneic setting, much evidence suggests that mobilized T-cell alloreactivity is tempered by G-CSF, probably with the mediation of dendritic cells, even though no clear correlation with GVL and GVHD has been found. Plerixafor is not approved in healthy donors yet; early data suggest it might mobilize a GVHD protective balance of immune effectors, but further studies are needed to define its role in allogeneic transplant.

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G-CSF downregulates natural killer cell-mediated cytotoxicity in donors for hematopoietic SCT

Cited by 30 publications

References 34 publications

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Effect of the in vivo application of granulocyte colony‐stimulating factor on NK cells in bone marrow and peripheral blood

Low blood lymphocyte count at 30 days post transplant predicts worse acute GVHD and survival but not relapse in a large retrospective cohort

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

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