scholarly journals Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Haitao Sun ◽  
Tianzhu Yu ◽  
Xin Li ◽  
Yangyang Lei ◽  
Jianke Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Near Infrared ◽  
Treatment Strategies ◽  
Dendritic Cell Maturation ◽  
System Response ◽  
Toll Like Receptor ◽  
Programmed Death ◽  
Tumor Region ◽  
Thermosensitive Liposomes ◽  
Immune System Response

Abstract Background The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. Results Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with a NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses. Conclusion CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy. Graphical Abstract

scholarly journals Second near-infrared photothermal-amplified immunotherapy using photoactivatable composite nanostimulators

2021 ◽  
Author(s):  
Haitao Sun ◽  
Tianzhu Yu ◽  
Xin Li ◽  
Yangyang Lei ◽  
Jianke Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Near Infrared ◽  
Treatment Strategies ◽  
Dendritic Cell Maturation ◽  
System Response ◽  
Toll Like Receptor ◽  
Programmed Death ◽  
Tumor Region ◽  
Thermosensitive Liposomes ◽  
Immune System Response

Abstract Background The construction of a nanoimmune controlled-release system that spatiotemporally recognizes tumor lesions and stimulates the immune system response step by step is one of the most potent cancer treatment strategies for improving the sensitivity of immunotherapy response. Results Here, a composite nanostimulator (CNS) was constructed for the release of second near-infrared (NIR-II) photothermal-mediated immune agents, thereby achieving spatiotemporally controllable photothermal-synergized immunotherapy. CNS nanoparticles comprise thermosensitive liposomes as an outer shell and are internally loaded with an NIR-II photothermal agent, copper sulfide (CuS), toll-like receptor-9 (TLR-9) agonist, cytosine-phospho-guanine oligodeoxynucleotides, and programmed death-ligand 1 (PD-L1) inhibitors (JQ1). Following NIR-II photoirradiation, CuS enabled the rapid elevation of localized temperature, achieving tumor ablation and induction of immunogenic cell death (ICD) as well as disruption of the lipid shell, enabling the precise release of two immune-therapeutical drugs in the tumor region. Combining ICD, TLR-9 stimulation, and inhibited expression of PD-L1 allows the subsequent enhancement of dendritic cell maturation and increases infiltration of cytotoxic T lymphocytes, facilitating regional antitumor immune responses. Conclusion CNS nanoparticle-mediated photothermal-synergized immunotherapy efficiently suppressed the growth of primary and distant tumors in two mouse models and prevented pulmonary metastasis. This study thus provides a novel sight into photo-controllably safe and efficient immunotherapy.

Beyond dsRNA: Toll-like receptor 3 signalling in RNA-induced immune responses

2014 ◽  
Vol 458 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Megumi Tatematsu ◽  
Tsukasa Seya ◽  
Misako Matsumoto
Keyword(s):  
Immune Responses ◽  
Transmembrane Protein ◽  
Wide Spectrum ◽  
Physiological Role ◽  
Structural Features ◽  
Dendritic Cell Maturation ◽  
Type I ◽  
Toll Like Receptor ◽  
Wide Range ◽  
Infection And Inflammation

The innate immune system recognizes pathogen- and damage-associated molecular patterns using pattern-recognition receptors that activate a wide range of signalling cascades to maintain host homoeostasis against infection and inflammation. Endosomal TLR3 (Toll-like receptor 3), a type I transmembrane protein, senses RNAs derived from cells with viral infection or sterile tissue damage, leading to the induction of type I interferon and cytokine production, as well as dendritic cell maturation. It has been accepted that TLR3 recognizes perfect dsRNA, but little has been addressed experimentally with regard to the structural features of virus- or host-derived RNAs that activate TLR3. Recently, a TLR3 agonist was identified, which was a virus-derived ‘structured’ RNA with incomplete stem structures. Both dsRNA and structured RNA are similarly internalized through clathrin- and raftlin-dependent endocytosis and delivered to endosomal TLR3. The dsRNA uptake machinery, in addition to TLR3, is critical for extracellular viral RNA-induced immune responses. A wide spectrum of TLR3 ligand structures beyond dsRNA and their delivery systems provide new insights into the physiological role of TLR3 in virus- or host-derived RNA-induced immune responses. In the present paper, we focus on the system for extracellular recognition of RNA and its delivery to TLR3.

scholarly journals Association of Toll-Like Cell Receptors TLR2 (p.Arg753GLN) and TLR4 (p.Asp299GLY) Polymorphisms with Indicators of General and Local Immunity in Patients with Atopic Dermatitis

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yury A. Tyurin ◽  
Anton F. Shamsutdinov ◽  
Nikolay N. Kalinin ◽  
Alsou A. Sharifullina ◽  
Irina D. Reshetnikova
Keyword(s):  
Atopic Dermatitis ◽  
Immune Responses ◽  
System Response ◽  
Immunological Parameters ◽  
Local Immunity ◽  
Innate And Adaptive Immunity ◽  
Immune System Response ◽  
Relationship Of ◽  
The Relationship ◽  
Control Study

A whole group of polymorphisms of genes involved in the formation of the epidermal barrier, immune responses, and their regulation is important in the formation of atopic phenotype. The purpose of the study is to determine the relationship of polymorphisms of genes of Toll-like receptors TLR2 and TLR4 with clinical and immunological parameters in atopic dermatitis patients in a “case-control” study. Polymorphisms of genes TLR2 (p.Arg753Gln) and TLR4 (Asp299Gly) were detected by PCR. Parameters of the state of innate and adaptive immunity were assessed by the level of local production of sIgA, cytokine profile of blood serum for IL-4, IL-10, and IFN-γ. Biological samples from 50 people with allergic pathology, aged 4.5 to 35 years, and 100 healthy individuals (controls) were analyzed. Observed dysregulation of cytokine production (IL-4, IL-10) in patients with heterozygous polymorphic genotypes probably reflects an imbalance of Th1/Th2/Th17 regulation of immune system response in these individuals.

Near-Infrared-II Nanoparticles for Cancer Imaging of Immune Checkpoint Programmed Death-Ligand 1 and Photodynamic/Immune Therapy

ACS Nano ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 515-525
Author(s):  
Qiang Liu ◽  
Jiangwei Tian ◽  
Ye Tian ◽  
Qinchao Sun ◽  
Dan Sun ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Near Infrared ◽  
Cancer Imaging ◽  
Immune Therapy ◽  
Programmed Death Ligand 1 ◽  
Programmed Death

scholarly journals NCMP-05. DECODING THE IMMUNE SYSTEM RESPONSE TO LEPTOMENINGEAL METASTASIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii124-ii124
Author(s):  
Jan Remsik ◽  
Xinran Tong ◽  
Ugur Sener ◽  
Danille Isakov ◽  
Yudan Chi ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Cells ◽  
Leptomeningeal Metastasis ◽  
System Response ◽  
Idle State ◽  
The Central Nervous System ◽  
Health And Disease ◽  
Immune System Response ◽  
Therapeutic Protocols ◽  
Brain And Spinal Cord

Abstract For decades, the central nervous system was considered to be an immune privileged organ with limited access to systemic immunity. However, the leptomeninges, the cerebrospinal fluid (CSF)-filled anatomical structure that protects the brain and spinal cord, represent a relatively immune-rich environment. Despite the presence of immune cells, complications in the CSF, such as infectious meningitis and a neurological development of cancer known as leptomeningeal metastasis, are difficult to treat and are frequently fatal. We show that immune cells entering the CSF are held in an ‘idle’ state that limits their cytotoxic arsenal and antigen presentation machinery. To understand this underappreciated neuroanatomic niche, we used unique mouse models and rare patient samples to characterize its cellular composition and critical signaling events in health and disease at a single-cell resolution. Revealing the mediators of CSF immune response will allow us to re-evaluate current therapeutic protocols and employ rational combinations with immunotherapies, therefore turning the patient’s own immune system into an active weapon against pathogens and cancer.

scholarly journals An amphiphilic dendrimer as a light-activable immunological adjuvant for in situ cancer vaccination

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yongchao Wang ◽  
Ningqiang Gong ◽  
Chi Ma ◽  
Yuxuan Zhang ◽  
Hong Tan ◽  
...  
Keyword(s):  
Near Infrared ◽  
Infrared Light ◽  
Immune Memory ◽  
Toll Like Receptor ◽  
Tumour Site ◽  
Adjuvant Effect ◽  
Cancer Vaccination ◽  
Tumour Metastasis

AbstractImmunological adjuvants are essential for successful cancer vaccination. However, traditional adjuvants have some limitations, such as lack of controllability and induction of systemic toxicity, which restrict their broad application. Here, we present a light-activable immunological adjuvant (LIA), which is composed of a hypoxia-responsive amphiphilic dendrimer nanoparticle loaded with chlorin e6. Under irradiation with near-infrared light, the LIA not only induces tumour cell lysis and tumour antigen release, but also promotes the structural transformation of 2-nitroimidazole containing dendrimer to 2-aminoimidazole containing dendrimer which can activate dendritic cells via the Toll-like receptor 7-mediated signaling pathway. The LIA efficiently inhibits both primary and abscopal tumour growth and induces strong antigen-specific immune memory effect to prevent tumour metastasis and recurrence in vivo. Furthermore, LIA localizes the immunological adjuvant effect at the tumour site. We demonstrate this light-activable immunological adjuvant offers a safe and potent platform for in situ cancer vaccination.

Induction of dendritic cell maturation and modulation of dendritic cell-induced immune responses by prostaglandins

2000 ◽  
Vol 292 (9) ◽  
pp. 437-445 ◽  
Author(s):  
K. Steinbrink ◽  
L. Paragnik ◽  
H. Jonuleit ◽  
T. Tüting ◽  
J. Knop ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Immune Responses ◽  
Dendritic Cell Maturation ◽  
Cell Maturation
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