Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Dirks, Jan; Egli, Adrian; Sester, Urban; Sester, Martina; Hirsch, Hans H.

doi:10.1111/tid.12025

Cited by 28 publications

(28 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A high percentage of PD1+, CD38+ circulating T cells has also been found in other chronic diseases such as graft-versus-host disease [45] and chronic herpes virus infections [35,36]. In the latter it was linked to a reduced life span of the affected persons [46].…”

Section: Resultsmentioning

confidence: 99%

“…Patients with a monoallergy did not have these CD4+ , CD25 dim , CD38+, and PD-1+ T cells [8]. Initially it was speculated that the continued CD38+ and PD-1+ expression within the CD4+, CD25 dim cell fraction might be due to an ongoing infection by endogenous herpes viruses, as the PD1+/CD38+ phenotype was also observed in chronic herpes virus infections [35,36]. However, a viral analysis of the patients failed to document an ongoing herpes virus (cytomegalovirus and HHV6) infection.…”

Section: Patho-mechanism Of Mdhmentioning

confidence: 99%

See 1 more Smart Citation

Multiple Drug Hypersensitivity

Pichler

Srinoulprasert²,

Yun³

et al. 2017

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Multiple drug hypersensitivity (MDH) is a syndrome that develops as a consequence of massive T-cell stimulations and is characterized by long-lasting drug hypersensitivity reactions (DHR) to different drugs. The initial symptoms are mostly severe exanthems or drug rash with eosinophilia and systemic symptoms (DRESS). Subsequent symptoms due to another drug often appear in the following weeks, overlapping with the first DHR, or months to years later after resolution of the initial presentation. The second DHR includes exanthema, erythroderma, DRESS, Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), hepatitis, and agranulocytosis. The eliciting drugs can be identified by positive skin or in vitro tests. The drugs involved in starting the MDH are the same as for DRESS, and they are usually given in rather high doses. Fixed drug combination therapies like sulfamethoxazole/trimethoprim or piperacillin/tazobactam are frequently involved in MDH, and 30-40% of patients with severe DHR to combination therapy show T-cell reactions to both components. The drug-induced T-cell stimulation appears to be due to the p-i mechanism. Importantly, a permanent T-cell activation characterized by PD-1+/CD38+ expression on CD4+/CD25^low T cells can be found in the circulation of patients with MDH for many years. In conclusion, MDH is a drug-elicited syndrome characterized by a long-lasting hyperresponsiveness to multiple, structurally unrelated drugs with clinically diverse symptoms.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Patho-mechanism Of Mdhmentioning

confidence: 99%

Multiple Drug Hypersensitivity

Pichler

Srinoulprasert²,

Yun³

et al. 2017

Int Arch Allergy Immunol

View full text Add to dashboard Cite

show abstract

“…14,15 The combinatorial use of celecoxib with PD-1 mAb completely suppresses the upregulation of the inflammatory genes, including IL-1b and IL-6, both of which play critical roles in promoting tumor progression. 48,49 This observation provides the additional justification for the combined utilization of these two drugs for treating tumors.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 We next examined the expression of typical inflammatory molecules COX2, IL-1b, IL-6, iNOS and TNF-a, and of the anti-inflammatory molecule IL-10, and VEGF. While anti-PD-1 mAb delivery alone did not change the mRNA levels of iNOS, TNF-a, IL-10 and VEGF (data not shown), and the mRNA levels of COX2, IL-1b, IL-6, were increased ( Fig.…”

Section: Dual Delivery Of Celecoxib and Anti-pd-1 Mab Inhibits Angiogmentioning

confidence: 99%

Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity

et al. 2015

View full text Add to dashboard Cite

Two major challenges facing cancer immunotherapy are the relatively low therapeutic efficacy and the potential side effects. New drug delivery system and efficient drug combination are required to overcome these challenges. We utilize an alginate hydrogel system to locally deliver 2 FDA-approved drugs, celecoxib and programmed death 1 (PD-1) monoclonal antibody (mAb), to treat tumor-bearing mice. In two cancer models, B16-F10 melanoma and 4T1 metastatic breast cancer, the alginate hydrogel delivery system significantly improves the antitumor activities of celecoxib (CXB), PD-1 mAb, or both combined. These effects are associated with the sustained high concentrations of the drugs in peripheral circulation and within tumor regions. Strikingly, the simultaneous dual local delivery of celecoxib and PD-1 from this hydrogel system synergistically enhanced the presence of CD4 C inteferon (IFN)-g C and CD8C IFN-g C T cells within the tumor as well as in the immune system. These effects are accompanied with reduced CD4 C FoxP3 C regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs) in the tumor, reflecting a weakened immuosuppressive response. Furthermore, this combinatorial therapy increases the expression of two anti-angiogenic chemokines C-X-C motif ligand (CXCL) 9 and CXCL10, and suppresses the intratumoral production of interleukin (IL)-1, IL-6, and cycloxygenase-2 (COX2), suggesting a dampened pro-tumor angiogenic and inflammatory microenvironment. This alginate-hydrogel-mediated, combinatorial therapy of celecoxib and PD-1 mAb provides a potential valuable regimen for treating human cancer.

show abstract

“…However, studies have shown that blocking different coinhibitory molecules might exert a synergistic effect on immunotherapy for sepsis. [567273] With respect to the appropriate timing for anti-PD-1/PD-L1 antibody administration, Brahmamdam et al . [51] showed that when the anti-PD-1 antibody was given to mice 24 h after the induction of sepsis, the survival rate increased.…”

Section: Research On the Blockade Of The Programmed Cell Death-1/progmentioning

confidence: 99%

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway

Liu

2017

Chinese Medical Journal

View full text Add to dashboard Cite

Objective:Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment.Data Sources:Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database.Study Selection:English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated.Results:Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells.Conclusions:The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

show abstract

Blockade of programmed death receptor‐1 signaling restores expression of mostly proinflammatory cytokines in anergic cytomegalovirus‐specific T cells

Cited by 28 publications

References 23 publications

Multiple Drug Hypersensitivity

Multiple Drug Hypersensitivity

Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway

Contact Info

Product

Resources

About