AI Article Synopsis

  • The study investigates the effects of chemoimmunotherapy on the properties of natural killer (NK) cells in children with newly diagnosed high-risk neuroblastoma as part of a phase II clinical trial.
  • Results showed that while chemoimmunotherapy caused NK cell depletion initially, there was a significant recovery and increase in NK cell cytotoxicity by day 21 of treatment, correlating with tumor volume reduction.
  • The findings suggest a potential connection between CD56 expression on NK cells and tumor size changes, indicating that NK cell dynamics could be significant for treatment outcomes, warranting further research.

Article Abstract

Background: Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics, phenotype, and function is understudied.

Methods: We prospectively examined NK cell properties from 63 children with newly diagnosed neuroblastoma enrolled in a phase II trial (NCT01857934) and correlated our findings with tumor volume reduction after 2 courses of chemoimmunotherapy. NK cell studies were conducted longitudinally during chemoimmunotherapy and autologous hematopoietic cell transplantation (autoHCT) with optional haploidentical NK cell infusion and additional immunotherapy.

Results: Chemoimmunotherapy led to significant NK cytopenia, but complete NK cell recovery reliably occurred by day 21 of each therapy course as well as after autoHCT. Haploidentical NK cell infusion elevated the NK cell count transiently during autoHCT. NK cell cytotoxicity increased significantly during treatment compared with diagnosis. In addition, NK cells maintained their ability to respond to cytokine stimulation in culture longitudinally. Unsupervised cluster analysis of CD56 NK cell count and tumor volume at diagnosis and after two courses of chemoimmunotherapy identified two patient groups with distinct primary tumor sizes and therapy responses.

Conclusion: After profound NK cytopenia due to chemoimmunotherapy, endogenously reconstituted NK cells exhibit enhanced NK cytotoxicity compared with pretherapy measurements. Our data suggest a relationship between CD56 expression and tumor size before and after two courses of chemoimmunotherapy; however, future studies are necessary to confirm this relationship and its predictive significance.

Trial Registration Number: NCT01857934.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206969PMC
http://dx.doi.org/10.1136/jitc-2019-000176DOI Listing

Publication Analysis

Top Keywords

phase trial
12
courses chemoimmunotherapy
12
cell
10
cell kinetics
8
neuroblastoma enrolled
8
chemoimmunotherapy cell
8
tumor volume
8
haploidentical cell
8
cell infusion
8
cell count
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!