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Diminished cytolytic activity of γδ T cells with reduced DNAM-1 expression in neuroblastoma patients

Xiaolin Wang1, Wenjun Mou1, Wei Han2

  • 1Key Laboratory of Major Disease in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Laboratory of Tumor Immunology, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; Beijing Key Laboratory for Genetics of Birth Defects, MOE Key Laboratory of Major Diseases in Children, Center for Medical Genetics, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.

Clinical Immunology (Orlando, Fla.)
|April 19, 2019
PubMed

Insights

Neuroblastoma (NB) patients show reduced DNAM-1 expression on γδ T cells, impairing their ability to kill tumor cells. This suggests DNAM-1 is crucial for effective γδ T-cell immunotherapy in NB treatment.

Area of Science:

  • Immunology
  • Pediatric Oncology
  • Cancer Research

Background:

  • Neuroblastoma (NB) is a pediatric cancer with poor prognosis and high recurrence rates.
  • γδ T-cell immunotherapy is promising due to its potent anti-tumor activity.
  • Previous studies indicated increased γδ T-cell frequency in NB patients.

Purpose of the Study:

  • To investigate the function of γδ T cells in neuroblastoma patients.
  • To assess the role of DNAM-1 expression and its impact on γδ T-cell activity against NB.

Main Methods:

  • Analysis of circulating and expanded γδ T cells from NB patients.
  • Measurement of Interferon-gamma (IFN-γ) levels and DNAM-1 expression.
  • Assessment of γδ T-cell proliferation and cytolytic activity in co-culture systems.
  • Use of DNAM-1 neutralizing antibodies to evaluate its functional role.

Main Results:

  • NB patients exhibited reduced serum IFN-γ levels.
  • Decreased DNAM-1 expression was observed on both circulating and expanded NB γδ T cells.
  • NB γδ T cells showed impaired proliferation and reduced cytolytic activity against NB cell lines.
  • DNAM-1 blockade abolished the residual tumor cell killing by NB γδ T cells.

Conclusions:

  • DNAM-1 plays a critical role in the cytolytic function of γδ T cells against neuroblastoma.
  • Reduced DNAM-1 expression contributes to the impaired anti-tumor activity of γδ T cells in NB patients.
  • Targeting DNAM-1 may enhance γδ T-cell immunotherapy efficacy for neuroblastoma.
Keywords:
Cytolytic activityDNAM-1Neuroblastomaγδ T cells

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