NK Cell Reconstitution After Autologous Hematopoietic Stem Cell Transplantation: Association Between NK Cell Maturation Stage and Outcome in Multiple Myeloma

Abstract

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard of care for transplant-eligible patients with multiple myeloma (MM). Among factors that influence outcome after autoHSCT, it has been suggested that the number of natural killer (NK) cells plays an important role. However, the impact that different NK cell subsets and their phenotype could have in disease progression after autoHSCT are less clear. For this reason, we have phenotypically and functionally characterized NK cells during immune system reconstitution after autoHSCT in 54 MM patients. Shortly after leukocyte recovery, an extensive redistribution of NK cell subsets occurs in these patients. In addition, NK cells undergo a profound phenotypic change characterized, among others, by their increased proliferative capacity and immature phenotype. Importantly, MM patients who showed lower frequencies of the mature highly differentiated NKG2A-CD57+ NK cell subset at +30 and +100 days after autoHSCT experienced superior progression-free survival and had a longer time to the next treatment than those with higher frequencies. Our results provide significant insights into NK cell reconstitution after autoHSCT and suggest that the degree of NK cell maturation after autoHSCT affects the clinical outcome of MM patients treated with this therapeutic strategy.

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

“…NK cells undergo profound phenotypical changes following autoHSCT ( Jacobs et al., 2015 ; Orrantia et al., 2021 ). To gain further insight into other aspects of NK cell biology, as for example proliferation and metabolism, during subset reconstitution after autoHSCT, the gene expression profile of NK cells from patients with MM (cohort 1) undergoing autoHSCT were compared at three different time points: T1 (pre-transplantation), T2 (after leukocyte recovery or >1000 leukocytes/μL, usually around day 14 after autoHSCT) and T3 (30 days after autoHSCT).…”

“…However, these phenotypic changes were not maintained overtime ( Jacobs et al., 2015 ; Orrantia et al., 2021 ). Importantly, we have previously described an association between NK cells’ maturation stage after autoHSCT and the clinical outcome of patients with MM ( Orrantia et al., 2021 ). Thus, with the aim of acquiring a broader knowledge of NK cell biology and physiopathology, we performed RNA-sequencing (RNA-seq) of NK cells during their reconstitution after autoHSCT.…”

“…The phenotype diversity has also been observed when NK cell subsets reconstitution after autoHSCT was analyzed in patients with multiple myeloma (MM) and malignant lymphomas ( Jacobs et al., 2015 ; Orrantia et al., 2021 ). Specifically, immediately after autoHSCT, NK cells exhibited an immature phenotype and higher proliferation capacity ( Orrantia et al., 2021 ) and showed differential expression of killer immunoglobulin-like receptors (KIRs) ( Jacobs et al., 2015 ) compared to NK cells pre-transplant. However, these phenotypic changes were not maintained overtime ( Jacobs et al., 2015 ; Orrantia et al., 2021 ).…”

“…Specifically, immediately after autoHSCT, NK cells exhibited an immature phenotype and higher proliferation capacity ( Orrantia et al., 2021 ) and showed differential expression of killer immunoglobulin-like receptors (KIRs) ( Jacobs et al., 2015 ) compared to NK cells pre-transplant. However, these phenotypic changes were not maintained overtime ( Jacobs et al., 2015 ; Orrantia et al., 2021 ). Importantly, we have previously described an association between NK cells’ maturation stage after autoHSCT and the clinical outcome of patients with MM ( Orrantia et al., 2021 ).…”

The yin–yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma

“…Meanwhile, NK cell recovery is achieved until 30 days after autologous hematopoietic stem cell transplantation (auto-HSCT). Importantly, at +30 and +100 days after auto-HSCT, MM patients with a lower frequency of mature, well-differentiated NKG2A-CD57+ NK cell subsets had a better PFS to the next treatment than those with a higher frequency ( 98 ). This provides new insights into the importance and degree of differentiation in NK cell reconstitution, which may have a better prognosis of MM patients after auto-HSCT.…”