Decreased expression of programmed death-1 on CD8+ effector memory T lymphocytes correlates with the pathogenesis of type 1 diabetes

Shan, Yimei; Kong, Yinghong; Zhou, Yan; Guo, Jingjing; Shi, Qiyun; Li, Sicheng; Guo, Heming; Huang, Yi‐Ting; Ding, Sisi; Liu, Cuiping; Cao, Lei; Huang, Yun; Chen, Fang; Hu, Ji

doi:10.1007/s00592-021-01711-z

Cited by 2 publications

(2 citation statements)

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“…The first evidence of the expression of PD-1 on CD8+ T exhausted memory (Tem) cells in patients with T1DM came from the study of Shan et al that demonstrated: (i) a significant reduction in frequencies of PD-1+ CD8+ Tem in peripheral blood mononuclear cells (PBMCs) of patients with T1DM (40.73% ± 12.72 versus (vs.) 47.43 ± 15.56, p < 0.05); (ii) a significant reduction in PD-1+ CD8+ Tem cells in patients with T1DM with positivity for two or more types of islet autoantibodies compared to patients with positivity for one type of islet autoantibody (13.46% vs. 46.95 ± 12.72%, p < 0.05); (iii) a significant reduction in PD-1+ CD8+ central memory T (Tcm) cells in patients with two or more types of autoantibodies compared to other groups [43]. Additional findings from the study of Shan et al were: (i) positive correlation of the frequencies of PD-1+CD8+ Tem cells with fasting serum C-peptide levels (r = 0.4308, p < 0.05) and C-peptide levels 2 h after meal in T1DM patients (r = 0.5723, p < 0.01); (ii) negative correlation of the frequencies of PD-1+CD8+ Tem cells with the levels of glycated hemoglobulin (HbA1c) (r = −0.2992, p < 0.05); (iii) significant reduction in frequencies of PD-1+CD8+ Tem in the intervention group treated with anti-PD-1 mAbs compared to the control group (14.22 ± 6.455% vs. 27.69 ± 9.837%, p < 0.05) [43].…”

Section: The Role Of the Disinhibition Of Pd-1/pd-l1 Interaction In T...mentioning

confidence: 98%

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Deligiorgi

Trafalis

2023

IJMS

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The rubric of immune-related (ir) diabetes mellitus (DM) (irDM) encompasses various hyperglycemic disorders related to immune checkpoint inhibitors (ICPis). Beyond sharing similarities with conventional DM, irDM is a distinct, yet important, entity. The present narrative review provides a comprehensive overview of the literature regarding irDM published in major databases from January 2018 until January 2023. Initially considered rare, irDM is increasingly being reported. To advance the knowledge of irDM, the present review suggests a concerted vision comprising two intertwined aspects: a scientific-centered and a patient-centered view. The scientific-centered aspect addresses the pathophysiology of irDM, integrating: (i) ICPi-induced pancreatic islet autoimmunity in genetically predisposed patients; (ii) altered gut microbiome; (iii) involvement of exocrine pancreas; (iv) immune-related acquired generalized lipodystrophy. The patient-centered aspect is both nurtured by and nurturing the four pillars of the scientific-centered aspect: awareness, diagnosis, treatment, and monitoring of irDM. The path forward is a multidisciplinary initiative towards: (i) improved characterization of the epidemiological, clinical, and immunological profile of irDM; (ii) standardization of reporting, management, and surveillance protocols for irDM leveraging global registries; (iii) patient stratification according to personalized risk for irDM; (iv) new treatments for irDM; and (v) uncoupling ICPi efficacy from immunotoxicity.

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Section: The Role Of the Disinhibition Of Pd-1/pd-l1 Interaction In T...mentioning

confidence: 98%

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Deligiorgi

Trafalis

2023

IJMS

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“…PD-1 deficiency specifically accelerates the development of subacute T1D in NOD mice ( 136 , 138 , 139 ). Downregulation of PD-1/PD-L1 on CD4+ and CD8+ T cells in patients with T1D is dynamically recovered in partial remission but decreased again after the partial remission phase ( 140 , 141 ). Thus, the above-mentioned results suggest that PD-1/PD-L1 may be a potential target for T1D therapy.…”

Section: Potential Clinical Application Of Immune Checkpoint Molecule...mentioning

confidence: 99%

Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes

Ding

Yang²,

Lin³

et al. 2023

Front. Endocrinol.

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BackgroundConsidered a significant risk to health and survival, type 1 diabetes (T1D) is a heterogeneous autoimmune disease characterized by hyperglycemia caused by an absolute deficiency of insulin, which is mainly due to the immune-mediated destruction of pancreatic beta cells.Scope of reviewIn recent years, the role of immune checkpoints in the treatment of cancer has been increasingly recognized, but unfortunately, little attention has been paid to the significant role they play both in the development of secondary diabetes with immune checkpoint inhibitors and the treatment of T1D, such as cytotoxic T-lymphocyte antigen 4(CTLA-4), programmed cell death protein-1(PD-1), lymphocyte activation gene-3(LAG-3), programmed death ligand-1(PD-L1), and T-cell immunoglobulin mucin protein-3(TIM-3). Here, this review summarizes recent research on the role and mechanisms of diverse immune checkpoint molecules in mediating the development of T1D and their potential and theoretical basis for the prevention and treatment of diabetes.Major conclusionsImmune checkpoint inhibitors related diabetes, similar to T1D, are severe endocrine toxicity induced with immune checkpoint inhibitors. Interestingly, numerous treatment measures show excellent efficacy for T1D via regulating diverse immune checkpoint molecules, including co-inhibitory and co-stimulatory molecules. Thus, targeting immune checkpoint molecules may exhibit potential for T1D treatment and improve clinical outcomes.

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Decreased expression of programmed death-1 on CD8+ effector memory T lymphocytes correlates with the pathogenesis of type 1 diabetes

Cited by 2 publications

References 41 publications

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

A Concerted Vision to Advance the Knowledge of Diabetes Mellitus Related to Immune Checkpoint Inhibitors

Mechanisms and therapeutic strategies of immune checkpoint molecules and regulators in type 1 diabetes

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