DNT Cell-based Immunotherapy: Progress and Applications

Li, Yingrui; Dong, Kang; Fan, Xiang; Xie, Jun; Wang, Miao; Fu, Songtao; Li, Qin

doi:10.7150/jca.39717

Cited by 25 publications

(31 citation statements)

References 111 publications

(141 reference statements)

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“…Given that clinical application of both DNTs and Ide have been tried, application of these findings into clinic might contribute to enhancing the efficacy and durability of response [ 97 ]. What is more, DNTs therapy could significantly reduce lung tumor growth in patient-derived xenograft models but could not eradicate the full extent of the tumor cells [ 98 ].…”

Section: Development and Subgroups Of Dntsmentioning

confidence: 99%

Application of double-negative T cells in haematological malignancies: recent progress and future directions

2022

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Haematologic malignancies account for a large proportion of cancers worldwide. The high occurrence and mortality of haematologic malignancies create a heavy social burden. Allogeneic haematopoietic stem cell transplantation is widely used in the treatment of haematologic malignancies. However, graft-versus-host disease and relapse after allogeneic haematopoietic stem cell transplantation are inevitable. An emerging treatment method, adoptive cellular therapy, has been effectively used in the treatment of haematologic malignancies. T cells, natural killer (NK) cells and tumour-infiltrating lymphocytes (TILs) all have great potential in therapeutic applications, and chimeric antigen receptor T (CAR-T) cell therapy especially has potential, but cytokine release syndrome and off-target effects are common. Efficient anticancer measures are urgently needed. In recent years, double-negative T cells (CD3+CD4−CD8−) have been found to have great potential in preventing allograft/xenograft rejection and inhibiting graft-versus-host disease. They also have substantial ability to kill various cell lines derived from haematologic malignancies in an MHC-unrestricted manner. In addition, healthy donor expanded double-negative T cells retain their antitumour abilities and ability to inhibit graft-versus-host disease after cryopreservation under good manufacturing practice (GMP) conditions, indicating that double-negative T cells may be able to be used as an off-the-shelf product. In this review, we shed light on the potential therapeutic ability of double-negative T cells in treating haematologic malignancies. We hope to exploit these cells as a novel therapy for haematologic malignancies.

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Section: Development and Subgroups Of Dntsmentioning

confidence: 99%

Application of double-negative T cells in haematological malignancies: recent progress and future directions

2022

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“…A series of previous studies indicated that DNT cells were predominately memory phenotype in SIV infection, and have a T helper function, secreting CD4-like cytokines (IL-4, IL-17, IFN-γ and TNF-α) in SIV-infected or healthy monkeys such as sooty mangabeys ( 18 – 20 ). However, most studies identified these cells as similar to regulatory T cells (Tregs), which could suppress T cells, B cells, dendritic cells, and NK cells in graft-versus-host disease, autoimmune diseases, and infectious disease ( 21 – 23 ). Elevated DNT cells were reported to associate with the control of immune activation in both primary HIV-1 infection and IRs, suggesting the role of DNT cells in disease progression and immune reconstitution of PLWH ( 23 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Wang

Zhang

et al. 2022

Front. Immunol.

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Although extensive use of antiretroviral therapy (ART) has made great progress in controlling HIV replication and improving CD4+ T cell recovery, the immune reconstitution remained insufficient in some patients, who were defined as poor immunological responders (PIRs). These PIRs were at a high risk of AIDS-related and non-AIDS complications, resulting in higher morbidity and mortality rate. Thus, it is a major challenge and urgently needed to distinguish PIRs early and improve their immune function in time. Immune activation is a key factor that leads to impaired immune reconstitution in people living with HIV (PLWH) who are receiving effective ART. Double negative T cells (DNT) were reported to associate with the control of immune activation during HIV infection. However, the precise mechanisms by which DNT cells exerted their suppressive capacity during HIV infection remained puzzled. CD73, both a soluble and a membrane-bound form, display immunosuppressive effects through producing adenosine (ADO). Thus, whether DNT cells expressed CD73 and mediated immune suppression through CD73-ADO pathway needs to be investigated. Here, we found a significant downregulation of CD73 expression on DNT cells in treatment-naïve PLWH (TNs) compared to healthy controls, accompanied with increased concentration of sCD73 in plasma. Both the frequency of CD73+ DNT cells and the level of plasma sCD73 recovered after ART treatment. However, PIRs showed decreased percentage of CD73+ DNT cells compared to immunological responders (IRs). The frequency of CD73+ DNT cells was positively correlated with CD4+ T cell count and CD4/CD8 ratio, and negatively correlated with immune activation in PLWH. The level of sCD73 also showed a negative correlation to CD4+ T cell count and CD4/CD8 ratio. More importantly, in the present cohort, a higher level of sCD73 at the time of initiating ART could predict poor immune reconstitution in PLWH after long-term ART. Our findings highlighted the importance of CD73+ DNT cells and sCD73 in the disease progression and immune reconstitution of PLWH, and provided evidences for sCD73 as a potential biomarker of predicting immune recovery.

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“…DNT cells account for 1–3% of total lymphocytes in peripheral blood and play an important role in various diseases' immunopathogenesis [ 14 – 16 ]. In patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), the percentage of DNT cells was elevated along with renal damage [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Correlation between Peripheral T Cell Subsets and the Activity of Thyroid-Associated Ophthalmopathy

Liang

et al. 2022

International Journal of Endocrinology

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Introduction. Thyroid-associated ophthalmopathy (TAO) is the most common orbital immunological disease in adults. T cells play an important role in the pathogenesis of TAO. However, our knowledge of the circulating T cell subsets in TAO is limited. Objective. To investigate the circulating T cell subsets in TAO and the correlations between them and the activity of TAO. Methods. Thirty-eight TAO patients (19 active and 19 nonactive) were enrolled. The absolute number and percentage of total lymphocytes, CD3+T cells, CD4+T cells, CD8+ T cells, CD3+CD4-CD8-T cells (DNT cells), and CD3+CD4+CD8+ T cells (DPT cells) in peripheral blood were measured by flow cytometer. Results. TAO patients were divided into the active group and the nonactive group by the clinical activity score (CAS). The mean CAS was 4 ± 1.11 in the active group and 1.47 ± 0.61 in the nonactive group. No statistical differences were found in gender, age, and the levels of FT3, FT4, TSH, and TRAb between the two groups. The percentage of DNT cells was lower in the active group than in the non-active group, and it was negatively correlated with CAS (r = −0.349, P = 0.032 ), but not the absolute number. The CD4/CD8 ratio, the absolute number and percentage of CD3+ T cells, CD4+ T cells, CD8+ T cells, and DPT cells did not differ between the two groups. ConclusionIn the present study, we found the percentage of DNT cells was significantly lesser in the active TAO than in the nonactive TAO, and it was negatively correlated with the activity of the TAO. It suggests that DNT cells may involve in the immunopathogenesis of TAO and can serve as a clinical biomarker of the disease activity.

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DNT Cell-based Immunotherapy: Progress and Applications

Cited by 25 publications

References 111 publications

Application of double-negative T cells in haematological malignancies: recent progress and future directions

Application of double-negative T cells in haematological malignancies: recent progress and future directions

Decreased CD73+ Double-Negative T Cells and Elevated Level of Soluble CD73 Correlated With and Predicted Poor Immune Reconstitution in HIV-Infected Patients After Antiretroviral Therapy

Correlation between Peripheral T Cell Subsets and the Activity of Thyroid-Associated Ophthalmopathy

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