Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity

Álvarez‐Sierra, Daniel; Marín-Sánchez, Ana; Ruiz-Blazquez, Paloma; Jesús‐Gil, Carmen de; Iglesias-Felip, Carmela; González, O.; Casteràs, Anna; Costa, Roser Ferrer; Nuciforo, Paolo; Colobran, Roger; Pujol-Borrell, Ricardo

doi:10.1016/j.jaut.2019.05.013

Cited by 68 publications

(59 citation statements)

References 53 publications

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“…These therapeutic drugs included PD-1 inhibitors Nivolumab (Opdivo) [ 8 , 9 ] as well as Pembrolizumab (Keytruda) [ 10 , 11 ], and PD-L1 inhibitors Atezolizumab (Tecentriq) [ 12 ], Durvalumab (Imfinzi) [ 13 ] and Avelumab (Bavencio) [ 14 ]. Previous data indicated that cancer cells derived PD-L1 regulated the activity of CD8 + T cell activity [ 15 , 16 ], which was a pivotal component of the cellular immune response in tumor development [ 17 , 18 ]. Mechanistically, cancer cells derived PD-L1 induced dysfunctions of CD8 + T cell contributed to immune evasion and disabled immune surveillance [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Hong

Xue

Jiang

et al. 2020

J Exp Clin Cancer Res

250

194

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Background Non-small cell lung cancer (NSCLC) cells derived intracellular and extracellular programmed cell death ligand 1 (PD-L1) promoted cancer progression and drug resistance, and facilitated tumor immune evasion. However, the detailed molecular mechanisms are still largely unknown. In the present study, we aimed to explore the role of circular RNA circ-CPA4/let-7 miRNA/PD-L1 axis in the regulation of NSCLC progression, drug resistance and tumor immune microenvironment. Methods Real-Time qPCR and Western Blot analysis were conducted to examine gene expressions at transcriptional and translated levels, respectively. The regulatory mechanisms of circ-CPA4, let-7 miRNA and PD-L1 were validated by dual-luciferase reporter gene system and RNA pull-down assay. Cell growth and apoptosis were determined by CCK-8 assay, colony formation assay and Annexin V-FITC/PI double staining assay. Cell mobility was evaluated by transwell assay. Results Circ-CPA4 and PD-L1 were high-expressed, while let-7 miRNA was low-expressed in NSCLC cells and cancer tissues compared to the human bronchial epithelial (HBE) cells and their paired clinical normal adjacent tissues, respectively. Besides, knock-down of circ-CPA4 inhibited cell growth, mobility and epithelial-mesenchymal transition (EMT), and promoted cell death in NSCLC cells by downregulating PD-L1 through serving as a RNA sponge for let-7 miRNA. In addition, the NSCLC cells derived PD-L1-containing exosomes promoted cell stemness and increased resistance of NSCLC cells to cisplatin. Notably, by co-culturing the NSCLC cells with CD8 + T cells isolated from human peripheral blood mononuclear cells (hPBMCs) in a transwell co-culturing system, we found that NSCLC cells inactivated CD8 + T cells in a secreted PD-L1-dependent manner. Further results suggested that circ-CPA4 also positively regulated exosomal PD-L1, and the NSCLC cells with circ-CPA4 ablation re-activated CD8 + T cells in the co-culturing system. Conclusion Taken together, circ-CPA4 regulated cell growth, mobility, stemness and drug resistance in NSCLC cells and inactivated CD8 + T cells in the tumor immune microenvironment through let-7 miRNA/PD-L1 axis.

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Section: Introductionmentioning

confidence: 99%

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Hong

Xue

Jiang

et al. 2020

J Exp Clin Cancer Res

250

194

View full text Add to dashboard Cite

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“…A recent study showed that PD‐1 + CD4 + T cells were remarkably increased among intrathyroidal lymphocytes of Graves’ disease patients. Furthermore, programmed cell death ligand‐1 (PD‐L1) was expressed in epithelial thyroid follicular cell clusters in their thyroid tissues. These findings suggest that the PD‐1/PD‐L1 pathway plays an important role in regulating thyroid autoimmunity, including Graves’ disease.…”

Section: Discussionmentioning

confidence: 97%

“…The detailed mechanism for the development of anti‐PD‐1 therapy‐associated Graves’ disease remains unknown. A recent study showed that PD‐1 + CD4 + T cells were remarkably increased among intrathyroidal lymphocytes of Graves’ disease patients. Furthermore, programmed cell death ligand‐1 (PD‐L1) was expressed in epithelial thyroid follicular cell clusters in their thyroid tissues.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death‐1 therapy: A case report

Kurihara

Oikawa

Nakajima

et al. 2020

J of Diabetes Invest

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We present the first case of simultaneous development of Graves' disease and type 1 diabetes during anti-programmed cell death 1 therapy. A 48-year-old man with parotid gland adenocarcinoma and lung metastasis had received five courses of nivolumab. Fourteen days after administration of the sixth course, his casual plasma glucose and hemoglobin A1c levels were 379 mg/dL and 7.2%, respectively. Furthermore, thyrotoxicosis was detected with a blood test. Serum total ketone body and thyroid-stimulating hormone receptor antibody levels increased, and serum C-peptide level decreased to 0.01 ng/mL thereafter. Thus, we concluded that he simultaneously developed anti-programmed cell death 1 therapy-associated type 1 diabetes and Graves' disease. Among Japanese patients with autoimmune polyglandular syndrome type III, the frequency of human leukocyte antigen-DRB1*04:05 is higher in those with both type 1 diabetes and Graves' disease. Our case had human leukocyte antigen-DRB1*04:05, which might be associated with the simultaneous development of the two diseases.

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“…[ 79,181,182] FoxP3 D/I Anti-inflammatory gene; the low expression and splice variants of FoxP3 induce Treg function defect and further impair the expression level of CD4 + CD25 + FoxP + cells, which may increase the risk of miscarriage.…”

Section: Immune System Disordersmentioning

confidence: 99%

“…For example, in an animal-based experiment 21 , the augmented coexpression of PD-1 and Tim-3 on CD4 + T cells promoted the predominant production of Th2 cells, and the increased secretion of Th2-type cytokines, such as IL-4 and IL-10, contributed to maintaining normal pregnancy. Although many studies have revealed that PD-1 and programmed cell death-ligand 1 (PD-L1) are highly expressed in HT tissues 34 , 48 , 79 , 80 regardless of whether differentiated thyroid carcinoma (DTC) coexists, it seems to be the response to HT conditions in the immune microenvironment. However, the poor suppressive function of the moderating effect is unable to modify the inflammatory phenomenon in the thyroid and accidentally promotes the metastasis of DTC 80 , 81 .…”

Section: Immune System Disordersmentioning

confidence: 99%

The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities

Min¹,

Wang²,

Chen³

et al. 2020

Int. J. Med. Sci.

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Hashimoto's thyroiditis (HT) is the most prevalent autoimmune thyroid disease (ATD) worldwide and is strongly associated with miscarriage and even recurrent miscarriage (RM). Moreover, with a deepening understanding, emerging evidence has shown that immune dysfunctions caused by HT conditions, including imbalanced subsets of CD4+ T-helper cells, B regulatory (Breg) cells, high expression levels of CD56dim natural killer (NK) cells, and cytokines, possibly play an important role in impairing maternal tolerance to the fetus. In recent years, unprecedented progress has been made in recognizing the specific changes in immune cells and molecules in patients with HT, which will be helpful in exploring the mechanism of HT-related miscarriage. Based on these findings, research investigating some potentially more effective treatments, such as selenium (Se), vitamin D3, and intravenous immunoglobulin (IVIG), has been well developed over the past few years. In this review, we highlight some of the latest advances in the possible immunological pathogenesis of HT-related miscarriage and focus on the efficacies of treatments that have been widely introduced to clinical trials or practice described in the most recent literature.

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Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity

Cited by 68 publications

References 53 publications

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Circular RNA circ-CPA4/ let-7 miRNA/PD-L1 axis regulates cell growth, stemness, drug resistance and immune evasion in non-small cell lung cancer (NSCLC)

Simultaneous development of Graves’ disease and type 1 diabetes during anti‐programmed cell death‐1 therapy: A case report

The exploration of Hashimoto's Thyroiditis related miscarriage for better treatment modalities

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