Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).

Research progress of the mechanism of double negative T cell in the treatment of pancreatic tumor / 国际外科学杂志

Double negative T cell is a kind of special regulatory T cell with a cell phenotype of TCR + CD3 + CD4-CD8-.It plays an important role in many diseases such as autoimmune diseases,tumor immunity,transplant rejection and allergic diseases by expressing unique surface markers and secreting unique effector factors.Pancreatic cancer is a poorly diagnosed malignant tumor of the digestive system,and its early diagnosis rate is not high,the treatment is still based on radical tumor resection.Although the surgical technique is continuously improved,the 5-year survival rate has not improved significantly.At present,there is still a lack of effective treatment.In recent years,double negative T cell has become a new research hotspot in tumor immunity,bringing new hope for the treatment of pancreatic cancer.According to different types of T cell antigen receptor (TCR) expression,double negative T cell can be divided into TCRαβT cell and TCRγδT cell.This review focuses on the source of double negative T cell and possible molecular mechanisms in cancer therapy.

Effector molecules of mouse CD4 T cell converted double negative T cell / 国际外科学杂志

Objective To investigate the function characteristics of CD4 T cell converted double negative T cell and provide a basis for further insight into the characteristics of mouse converted double negative T cell.Methods The gene expression profile was analyzed by transcriptome sequencing and protein mass spectrometry.The expression of cell active marker CD44,CD69 and OX40 was investigated by flow cytometry and the cytotoxicity of mouse double negative T cell was verified by CFSE staining.Results Mouse CD4 T cell converted double negative T cell expressed cell phenotype that differed from other mature CI4 T cells.Mouse converted double negative T cell expressed high level of active marker of CD44,CD69 and OX40.Cytotoxicity of PrfO DN T was significantly reduced.Conclusions Mouse CD4 T cell converted double negative T cell has distinguishing cell phenotypes,that are not identical to other mature CD4 T cells.Mouse double negative T cell overexpresses cell activation marker and cytotoxic cytokines.The immune suppressive function of mouse double negative T cell is mainly dependent on perforin pathway.

Progress of autoimmune lymphoproliferactive syndrome / 国际儿科学杂志

Autoimmune lymphoproliferactive syndrome is a rare group disorders associated with self stability and immune tolerance of lymphocyte due to genetic mutation which affects the lymphocyte apoptosis .The clinical manifestations comprise lymphoproliferation, development of autoimmunity and malignancies.The pathogenesis and clinical features are complex ALPS were easily missed and no case had been reported until now in China.