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

Xiaolin Wang; Wenjun Mou; Wei Han; Yue Xi; Xi Chen; Hui Zhang; Hong Qin; Huanmin Wang; Xiaoli Ma; Jingang Gui

doi:10.1016/j.clim.2019.04.006

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

Clin Immunol. 2019 Jun:203:63-71. doi: 10.1016/j.clim.2019.04.006. Epub 2019 Apr 15.

Authors

Xiaolin Wang¹, Wenjun Mou¹, Wei Han², Yue Xi¹, Xi Chen¹, Hui Zhang¹, Hong Qin², Huanmin Wang², Xiaoli Ma³, Jingang Gui⁴

Affiliations

¹ Key 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.
² Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
³ Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China.
⁴ Key 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. Electronic address: [email protected].

PMID: 30999035
DOI: 10.1016/j.clim.2019.04.006

Abstract

Neuroblastoma is one of the children's malignant tumors with poor prognosis, as well as high recurrence and metastasis rates after surgical removal and chemotherapy. γδ T-cell based immunotherapy receives increasing attention thanks to the strong cytolytic activity to tumor cells. Our previous data revealed a significant increase in circulating γδ T-cell frequency in NB patients. In the present study, we found that beside a reduction of IFN-γ in serum of NB patients, DNAM-1 expression decreased in both circulating and PAM-expanded NB γδ T cells. Upon PAM stimulation, NB γδ T cells showed a reduced level of cell proliferation. In addition, the cytolytic activity of NB γδ T cells to NB cell lines was proved to be attenuated in a co-culture system. The fact that DNAM-1 neutralizing antibody abolished the tumor cell killing accentuates the indispensable role of DNAM-1 molecule in γδ T-cell cytolytic function.

Keywords: Cytolytic activity; DNAM-1; Neuroblastoma; γδ T cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Neutralizing / metabolism
Antigens, Differentiation, T-Lymphocyte / immunology
Antigens, Differentiation, T-Lymphocyte / metabolism*
Cancer Vaccines / immunology*
Cell Line, Tumor
Cell Proliferation
Child, Preschool
Coculture Techniques
Cytotoxicity, Immunologic
Down-Regulation
Female
Humans
Immunotherapy, Adoptive / methods*
Interferon-gamma / blood
Male
Neuroblastoma / immunology
Neuroblastoma / therapy*
Receptors, Antigen, T-Cell, gamma-delta / metabolism
T Lineage-Specific Activation Antigen 1
T-Lymphocytes / immunology*
T-Lymphocytes / transplantation

Substances

Antibodies, Neutralizing
Antigens, Differentiation, T-Lymphocyte
T Lineage-Specific Activation Antigen 1
Cancer Vaccines
Receptors, Antigen, T-Cell, gamma-delta
Interferon-gamma