TLR9 expression is associated with PD-L1 expression and indicates a poor prognosis in patients with peripheral T-cell lymphomas

Qian, Jingrong; Meng, Hongxue; Lv, Bowen; Wang, Jie; Lu, Yingying; Li, Wenhui; Song, Zhao

doi:10.1016/j.prp.2019.152703

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…Thus, it may be leading to the increase in EBI3 ( 72 ) and PD-L1 ( 73 ) expression. TLR9 – a receptor for CpG – has also been shown to promote IL10 ( 65 ), EBI3 ( 74 ), and PD-L1 ( 75 ) expression ( Figure 5 ).…”

Section: Discussionmentioning

confidence: 99%

Differentially activated B cells develop regulatory phenotype and show varying immunosuppressive features: a comparative study

Zheremyan,

Ustiugova,

Uvarova

et al. 2023

Front. Immunol.

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Regulatory B lymphocytes (Bregs) are B cells with well-pronounced immunosuppressive properties, allowing them to suppress the activity of effector cells. A broad repertoire of immunosuppressive mechanisms makes Bregs an attractive tool for adoptive cell therapy for diseases associated with excessive activation of immune reactions. Such therapy implies Breg extraction from the patient’s peripheral blood, ex vivo activation and expansion, and further infusion into the patient. At the same time, the utility of Bregs for therapeutic approaches is limited by their small numbers and extremely low survival rate, which is typical for all primary B cell cultures. Therefore, extracting CD19+ cells from the patient’s peripheral blood and specifically activating them ex vivo to make B cells acquire a suppressive phenotype seems to be far more productive. It will allow a much larger number of B cells to be obtained initially, which may significantly increase the likelihood of successful immunosuppression after adoptive Breg transfer. This comparative study focuses on finding ways to efficiently manipulate B cells in vitro to differentiate them into Bregs. We used CD40L, CpG, IL4, IL21, PMA, and ionomycin in various combinations to generate immunosuppressive phenotype in B cells and performed functional assays to test their regulatory capacity. This work shows that treatment of primary B cells using CD40L + CpG + IL21 mix was most effective in terms of induction of functionally active regulatory B lymphocytes with high immunosuppressive capacity ex vivo.

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Section: Discussionmentioning

confidence: 99%

Differentially activated B cells develop regulatory phenotype and show varying immunosuppressive features: a comparative study

Zheremyan,

Ustiugova,

Uvarova

et al. 2023

Front. Immunol.

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“…TLR9 expression was also found to be associated with PD-L1 expression in peripheral T cell lymphoma. Elevated TLR9 and PD-L1 expressions were unfavorable prognostic factors for patients with peripheral T cell lymphoma [79]. In prostate cancer, high expression of TLR9 was associated with an increased likelihood of lymph node metastasis and poor prognosis.…”

Section: Tlr5mentioning

confidence: 97%

Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

Yang,

Jin,

Yeo

et al. 2024

Journal of Immunology Research

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Toll-like receptors (TLRs) belong to a germline-encoded protein family. These are pattern recognition receptors. They sense pathogen-associated molecular patterns (PAMPs). When this occurs, activation of the NF-ĸB pathway follows. This triggers the innate immune response of the host. The consequent inflammatory cytokine response usually contributes to the elimination of the pathogen. Activation of TLRs also induces an adaptive immune response by a cross-prime mechanism. This mechanism is employed in cancer immunotherapy. Using TLR ligands as adjuvants induces upregulation of costimulatory signals which in turn activates a cytotoxic leukocyte response against cancer cells. However, TLRs are also overexpressed in human cancer cells resulting in increased cell proliferation, migration, invasion, and angiogenesis. An intracellular adaptor, myeloid differentiation factor 88 (MyD88) probably mediates this process. MyD88 is intimately involved with all TLRs except TLR3. One consequence of the interaction between a TLR and MyD88 is activation of NF-ĸB. In this context of a variety of proinflammtory cytokines being produced, chronic inflammation may result. Inflammation is an important protective mechanism. However, chronic inflammation is also involved in carcinogenesis. Activation of NF-ĸB inhibits apoptosis and under certain circumstances, tumor cell survival. In this review, the potential therapeutic value of TLRs in immunotherapy and its role in oncogenesis are explored. The emerging use of artificial intelligence is mentioned.

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“…MyD88 activation and signaling through IRAK4 suppresses lytic reactivation of Epstein-Barr virus and favors its latency in B-cells [210]. In peripheral T-cell lymphomas, TLR-9 and programmed cell death-ligand 1 (PD-L1) expression are associated with poor survival [211]. Hence, targeting of both TLR-9 and PD-L1 is suggested to induce a sustained anti-tumor immunity [212].…”

Section: Tlr-9mentioning

confidence: 99%

Toll-like Receptors as Pro-Thrombotic Drivers in Viral Infections: A Narrative Review

Panzer

Kopp

Neumayer

et al. 2023

Cells

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Toll-like receptors (TLRs) have a critical role in the pathogenesis and disease course of viral infections. The induced pro-inflammatory responses result in the disturbance of the endovascular surface layer and impair vascular homeostasis. The injury of the vessel wall further promotes pro-thrombotic and pro-coagulatory processes, eventually leading to micro-vessel plugging and tissue necrosis. Moreover, TLRs have a direct role in the sensing of viruses and platelet activation. TLR-mediated upregulation of von Willebrand factor release and neutrophil, as well as macrophage extra-cellular trap formation, further contribute to (micro-) thrombotic processes during inflammation. The following review focuses on TLR signaling pathways of TLRs expressed in humans provoking pro-thrombotic responses, which determine patient outcome during viral infections, especially in those with cardiovascular diseases.

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TLR9 expression is associated with PD-L1 expression and indicates a poor prognosis in patients with peripheral T-cell lymphomas

Cited by 9 publications

References 37 publications

Differentially activated B cells develop regulatory phenotype and show varying immunosuppressive features: a comparative study

Differentially activated B cells develop regulatory phenotype and show varying immunosuppressive features: a comparative study

Multiple Factors Determine the Oncolytic or Carcinogenic Effects of TLRs Activation in Cancer

Toll-like Receptors as Pro-Thrombotic Drivers in Viral Infections: A Narrative Review

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