scholarly journals Lymphatic Specific Disruption in the Fine Structure of Heparan Sulfate Inhibits Dendritic Cell Traffic and Functional T Cell Responses in the Lymph Node

2014 ◽  
Vol 192 (5) ◽  
pp. 2133-2142 ◽  
Author(s):  
Xin Yin ◽  
Scott C. Johns ◽  
Daniel Kim ◽  
Zbigniew Mikulski ◽  
Catherina L. Salanga ◽  
...  
Keyword(s):  
Fine Structure ◽  
Lymph Node ◽  
T Cell ◽  
Dendritic Cell ◽  
Heparan Sulfate ◽  
T Cell Responses ◽  
Cell Responses

Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses

2020 ◽  
Author(s):  
Runhong Zhou ◽  
Kelvin Kai-Wang To ◽  
Yik-Chun Wong ◽  
Li Liu ◽  
Biao Zhou ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Responses ◽  
Cell Responses

scholarly journals Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity

Gut ◽  
2021 ◽  
pp. gutjnl-2020-322924
Author(s):  
Tuxiong Huang ◽  
Xiang-Yu Tan ◽  
Hui-Si Huang ◽  
Yu-Ting Li ◽  
Bei-Lei Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cell Response ◽  
T Cell Responses ◽  
Tumour Microenvironment ◽  
T Cell Response ◽  
Cell Responses ◽  
Cancer Associated Fibroblast ◽  
Anticancer Immunotherapy ◽  
Novel Therapeutic Strategies

ObjectiveSolid tumours respond poorly to immune checkpoint inhibitor (ICI) therapies. One major therapeutic obstacle is the immunosuppressive tumour microenvironment (TME). Cancer-associated fibroblasts (CAFs) are a key component of the TME and negatively regulate antitumour T-cell response. Here, we aimed to uncover the mechanism underlying CAFs-mediated tumour immune evasion and to develop novel therapeutic strategies targeting CAFs for enhancing ICI efficacy in oesophageal squamous cell carcinoma (OSCC) and colorectal cancer (CRC).DesignAnti-WNT2 monoclonal antibody (mAb) was used to treat immunocompetent C57BL/6 mice bearing subcutaneously grafted mEC25 or CMT93 alone or combined with anti-programmed cell death protein 1 (PD-1), and the antitumour efficiency and immune response were assessed. CAFs-induced suppression of dendritic cell (DC)-differentiation and DC-mediated antitumour immunity were analysed by interfering with CAFs-derived WNT2, either by anti-WNT2 mAb or with short hairpin RNA-mediated knockdown. The molecular mechanism underlying CAFs-induced DC suppression was further explored by RNA-sequencing and western blot analyses.ResultsA negative correlation between WNT2+ CAFs and active CD8+ T cells was detected in primary OSCC tumours. Anti-WNT2 mAb significantly restored antitumour T-cell responses within tumours and enhanced the efficacy of anti-PD-1 by increasing active DC in both mouse OSCC and CRC syngeneic tumour models. Directly interfering with CAFs-derived WNT2 restored DC differentiation and DC-mediated antitumour T-cell responses. Mechanistic analyses further demonstrated that CAFs-secreted WNT2 suppresses the DC-mediated antitumour T-cell response via the SOCS3/p-JAK2/p-STAT3 signalling cascades.ConclusionsCAFs could suppress antitumour immunity through WNT2 secretion. Targeting WNT2 might enhance the ICI efficacy and represent a new anticancer immunotherapy.

scholarly journals Dendritic Cell Targeting Effectively Boosts T Cell Responses Elicited by an HIV Multiepitope DNA Vaccine

2017 ◽  
Vol 8 ◽  
Author(s):  
Juliana de Souza Apostólico ◽  
Victória Alves Santos Lunardelli ◽  
Marcio Massao Yamamoto ◽  
Higo Fernando Santos Souza ◽  
Edecio Cunha-Neto ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Cell Targeting ◽  
Cell Responses

scholarly journals TriMix and tumor antigen mRNA electroporated dendritic cell vaccination plus ipilimumab: link between T-cell activation and clinical responses in advanced melanoma

2020 ◽  
Vol 8 (1) ◽  
pp. e000329 ◽  
Author(s):  
Brenda De Keersmaecker ◽  
Sofie Claerhout ◽  
Javier Carrasco ◽  
Isabelle Bar ◽  
Jurgen Corthals ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Clinical Response ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Advanced Melanoma ◽  
Dendritic Cell Vaccination ◽  
Cell Responses

BackgroundWe previously reported that dendritic cell-based mRNA vaccination plus ipilimumab (TriMixDC-MEL IPI) results in an encouraging rate of tumor responses in patients with pretreated advanced melanoma. Here, we report the TriMixDC-MEL IPI-induced T-cell responses detected in the peripheral blood.MethodsMonocyte-derived dendritic cells electroporated with mRNA encoding CD70, CD40 ligand, and constitutively active TLR4 (TriMix) as well as the tumor-associated antigens tyrosinase, gp100, MAGE-A3, or MAGE-C2 were administered together with IPI for four cycles. For 18/39 patients, an additional vaccine was administered before the first IPI administration. We evaluated tumor-associated antigen specific T-cell responses in previously collected peripheral blood mononuclear cells, available from 15 patients.ResultsVaccine-induced enzyme-linked immunospot assay responses detected after in vitro T-cell stimulation were shown in 12/15 patients. Immune responses detected in patients with a complete or partial response were significantly stronger and broader, and exhibited a higher degree of multifunctionality compared with responses in patients with stable or progressive disease. CD8+ T-cell responses from patients with an ongoing clinical response, either elicited by TriMixDC-MEL IPI or on subsequent pembrolizumab treatment, exhibited the highest degree of multifunctionality.ConclusionsTriMixDC-MEL IPI treatment results in robust CD8+ T-cell responses in a meaningful portion of stage III or IV melanoma patients, and obviously in patients with a clinical response. The levels of polyfunctional and multiantigen T-cell responses measured in patients with a complete response, particularly in patients evidently cured after 5+ years of follow-up, may provide a benchmark for the level of immune stimulation needed to achieve a durable clinical remission.Trial registration numberNCT01302496.

scholarly journals The Heparan Sulfate Mimetic PG545 Modulates T Cell Responses and Prevents Delayed-Type Hypersensitivity

2020 ◽  
Vol 11 ◽  
Author(s):  
Ievgen O. Koliesnik ◽  
Hedwich F. Kuipers ◽  
Carlos O. Medina ◽  
Svenja Zihsler ◽  
Dan Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Heparan Sulfate ◽  
T Cell Responses ◽  
Delayed Type Hypersensitivity ◽  
Cell Responses
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