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PD-1 blockade induces responses by inhibiting adaptive immune resistance
It is shown that pre-existing CD8+ T cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy.
IL-23 induces spondyloarthropathy by acting on ROR-γt+ CD3+CD4−CD8− entheseal resident T cells
- Jonathan P. Sherlock, B. Joyce-shaikh, +13 authors D. Cua
- Biology, MedicineNature Medicine
- 1 July 2012
The spondyloarthropathies are a group of rheumatic diseases that are associated with inflammation at anatomically distal sites, particularly the tendon-bone attachments (entheses) and the aortic…
Phase I Study of Pembrolizumab (MK-3475; Anti–PD-1 Monoclonal Antibody) in Patients with Advanced Solid Tumors
Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors, and Mechanism-based translational models with a focus on intratumor exposure prediction suggested robust clinical activity would be observed at doses ≥2 mg/kg every 3 weeks.
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy
The potential for TMB and a T cell–inflamed GEP to jointly predict clinical response to pembrolizumab was assessed in >300 patient samples with advanced solid tumors and melanoma across 22 tumor types from four KEYNOTE clinical trials.
PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.
- P. Nghiem, S. Bhatia, +28 authors M. Cheever
- MedicineThe New England journal of medicine
- 19 April 2016
First-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56% and effectiveness was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
IFN-g – related mRNA profile predicts clinical response to PD-1 blockade
Programmed death-1–directed (PD-1–directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-g is a critical driver of…
PD-L2 Expression in Human Tumors: Relevance to Anti-PD-1 Therapy in Cancer
- J. Yearley, Christopher Gibson, +10 authors T. Mcclanahan
- MedicineClinical Cancer Research
- 15 June 2017
Clinical response to pembrolizumab in patients with HNSCC with recurrent or metastatic disease may be related partly to blockade of PD-1/PD-L2 interactions, and therapy targeting bothPD-1 ligands may provide clinical benefit in these patients.
Thymic stromal lymphopoietin–elicited basophil responses promote eosinophilic esophagitis
A new mouse model of EoE-like disease that developed independently of IgE, but was dependent on TSLP and basophils is described, suggesting that the T SLP-basophil axis contributes to the pathogenesis of EeE and could be therapeutically targeted to treat this disease.
PD-L1 expression is a favorable prognostic factor in early stage non-small cell carcinoma.
PD-L1 is expressed at high levels in a significant proportion of NSCLC and appears to be a favorable prognostic factor in early stage disease, and further studies are recommended.
A Single Dose of Neoadjuvant PD-1 Blockade Predicts Clinical Outcomes in Resectable Melanoma
A rapid and potent anti-tumor response was identified, with 8 of 27 patients experiencing a complete or major pathological response after a single dose of anti-PD-1, all of whom remain disease free.