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https://www.readbyqxmd.com/read/29345283/regulation-of-programmed-death-ligand-in-the-human-head-and-neck-squamous-cell-carcinoma-microenvironment-is-mediated-through-matrix-metalloproteinase-mediated-proteolytic-cleavage
#1
Mayuko Hira-Miyazawa, Hiroyuki Nakamura, Mariko Hirai, Yutaka Kobayashi, Hiroko Kitahara, George Bou-Gharios, Shuichi Kawashiri
Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) is a devastating malignancy with a poor prognosis. According to recent clinical studies, tumour growth can be effectively reduced and survival can be improved by blocking the programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD‑L1) pathway. PD-L1 expression has been proposed as a potential causative mechanism, as HNSCC is highly immunosuppressive. However, anti-PD-1 treatment is beneficial only for certain patients...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29344609/generalized-lichen-nitidus-following-anti-pd-1-antibody-treatment
#2
Maria Cho, Yumi Nonomura, Yo Kaku, Teruki Dainichi, Atsushi Otsuka, Kenji Kabashima
No abstract text is available yet for this article.
January 17, 2018: JAMA Dermatology
https://www.readbyqxmd.com/read/29343652/painless-thyroiditis-and-fulminant-type-1-diabetes-mellitus-in-a-patient-treated-with-an-immune-checkpoint-inhibitor-nivolumab
#3
Kanako Sakurai, Satsuki Niitsuma, Ryota Sato, Kazuhiro Takahashi, Zenei Arihara
The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. Nivolumab, an anti-PD-1 monoclonal antibody, blocks PD-1 and can restore anti-cancer immune responses by disrupting the signal that inhibits T-cell activation. Nivolumab may induce endocrine-related adverse events, including hypophysitis, autoimmune thyroiditis, and type 1 diabetes mellitus. Here we report a 68-year-old female patient with advanced renal cell carcinoma who was treated with nivolumab...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#4
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#5
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339209/extratumoral-pd-1-blockade-does-not-perpetuate-obesity-associated-inflammation-in-esophageal-adenocarcinoma
#6
Karen C Galvin, Melissa J Conroy, Suzanne L Doyle, Margaret R Dunne, Ronan Fahey, Emma Foley, Katie E O'Sullivan, Derek G Doherty, Justin G Geoghegan, Narayanasamy Ravi, Cliona O'Farrelly, John V Reynolds, Joanne Lysaght
Checkpoint inhibitors, such as anti-PD-1 (Programmed death-1), are transforming cancer treatment for inoperable or advanced disease. As the incidence of obesity-associated malignancies, including esophageal adenocarcinoma (EAC) continue to increase and treatment with checkpoint inhibitors are being FDA approved for a broader range of cancers, it is important to assess how anti-PD-1 treatment might exacerbate pre-existing inflammatory processes at other sites. Outside the EAC tumor, the omentum and liver were found to be enriched with substantial populations of PD-1 expressing T cells...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29337446/-endocrinopathies-induced-by-immune-checkpoint-inhibitors
#7
Jaafar Jaafar, Maria Mavromati, Jacques Philippe
Immune checkpoint Inhibitors are new immunomodulatory treatments that have proven their anti-tumor efficacy in several advanced cancers. Nevertheless, their use has paved the way for multiple immunological adverse effects that affect many systems and organs including endocrine glands such as the pituitary, thyroid, adrenal and pancreas. Hypophysitis is the most common complication of anti-CTLA-4 monoclonal antibodies, while anti-PD-1 and anti-PD-L1 antibodies cause more thyroid complications. Adrenal insufficiency and type 1 diabetes are relatively less common...
January 10, 2018: Revue Médicale Suisse
https://www.readbyqxmd.com/read/29337311/dinaciclib-induces-immunogenic-cell-death-and-enhances-anti-pd-1-mediated-tumor-suppression
#8
Dewan Md Sakib Hossain, Sarah Javaid, Mingmei Cai, Chunsheng Zhang, Anandi Sawant, Marlene Hinton, Manjiri Sathe, Jeff Grein, Wendy Blumenschein, Elaine M Pinheiro, Alissa Chackerian
Blockade of the checkpoint inhibitor programmed death 1 (PD1) has demonstrated remarkable success in the clinic for the treatment of cancer; however, a majority of tumors are resistant to anti-PD1 monotherapy. Numerous ongoing clinical combination therapy studies will likely reveal additional therapeutics that complement anti-PD1 blockade. Recent studies found that immunogenic cell death (ICD) improves T cell responses against different tumors, thus indicating that ICD may further augment antitumor immunity elicited by anti-PD1...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29337305/host-expression-of-pd-l1-determines-efficacy-of-pd-l1-pathway-blockade-mediated-tumor-regression
#9
Heng Lin, Shuang Wei, Elaine M Hurt, Michael D Green, Lili Zhao, Linda Vatan, Wojciech Szeliga, Ronald Herbst, Paul W Harms, Leslie A Fecher, Pankaj Vats, Arul M Chinnaiyan, Christopher D Lao, Theodore S Lawrence, Max Wicha, Junzo Hamanishi, Masaki Mandai, Ilona Kryczek, Weiping Zou
Programmed death-1 receptor (PD-L1, B7-H1) and programmed cell death protein 1 (PD-1) pathway blockade is a promising therapy for treating cancer. However, the mechanistic contribution of host and tumor PD-L1 and PD-1 signaling to the therapeutic efficacy of PD-L1 and PD-1 blockade remains elusive. Here, we evaluated 3 tumor-bearing mouse models that differ in their sensitivity to PD-L1 blockade and demonstrated a loss of therapeutic efficacy of PD-L1 blockade in immunodeficient mice and in PD-L1- and PD-1-deficient mice...
January 16, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29331748/safety-and-efficacy-of-anti-programmed-death-1-antibodies-in-patients-with-cancer-and-pre-existing-autoimmune-or-inflammatory-disease
#10
François-Xavier Danlos, Anne-Laure Voisin, Valérie Dyevre, Jean-Marie Michot, Emilie Routier, Laurent Taillade, Stéphane Champiat, Sandrine Aspeslagh, Julien Haroche, Laurence Albiges, Christophe Massard, Nicolas Girard, Stéphane Dalle, Benjamin Besse, Salim Laghouati, Jean-Charles Soria, Christine Mateus, Caroline Robert, Emilie Lanoy, Aurélien Marabelle, Olivier Lambotte
OBJECTIVE: Patients with autoimmune or inflammatory disease (AID) are susceptible to immune-related adverse events (irAEs) when treated with immune check-point inhibitors (ICIs). We decided to analyse the safety and effectiveness of anti-PD-1 antibodies in AID patients and look for an association between the presence of pre-existing AID and the clinical outcome. METHODS: In a prospective study of the REISAMIC registry of grade ≥2 irAEs occurring in ICI-treated patients, we studied the associations between pre-existing AID on one hand and irAE-free survival, overall survival and best objective response rate on the other...
January 10, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29331646/progress-in-the-management-of-advanced-thoracic-malignancies-in-2017
#11
REVIEW
Roberto Ferrara, Laura Mezquita, Benjamin Besse
The treatment paradigm of non-small cell lung cancer (NSCLC) underwent a major revolution during the course of 2017. Immune checkpoint inhibitors (ICIs) brought remarkable improvements in response and overall survival (OS) both in unselected pretreated patients and in untreated patients with PD-L1 expression ≥50%. Furthermore, compelling preliminary results were reported for new combinations of anti-PD-1/PD-L1 agents with chemotherapy or anti-CTLA4 inhibitors. The success of the ICIs appeared to extend to patients with small cell lung cancer (SCLC), mesothelioma or thymic tumors...
January 10, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29326142/gut-bacteria-shape-response-to-checkpoint-inhibitor-therapy
#12
(no author information available yet)
The composition of patients' gut microbiomes influences whether they will respond to anti-PD-1 therapy, according to a trio of recently published studies. One of the studies also found that using antibiotics can reduce treatment efficacy, presumably by killing important species of gut bacteria. Now researchers are investigating how these findings can be used to increase the proportion of patients who respond to checkpoint inhibitor therapy.
January 11, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29326088/age-effects-of-distinct-immune-checkpoint-blockade-treatments-in-a-mouse-melanoma-model
#13
Álvaro Padrón, Vincent Hurez, Harshita B Gupta, Curtis A Clark, Sri Lakshmi Pandeswara, Bin Yuan, Robert S Svatek, Mary Jo Turk, Justin M Drerup, Rong Li, Tyler J Curiel
Cancer immunotherapy has shown remarkable recent progress. Immune checkpoint blocking antibodies have become the most successful anti-cancer agent class ever developed, with six distinct agents approved since 2011 for a wide variety of cancers. Although age is the biggest risk factor for cancer (aside from selected early-onset pediatric cancers), these agents were tested pre-clinically in young hosts, and there is remarkably little published on the effects of host age on treatment outcomes in pre-clinical studies or human clinical trials...
January 8, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29325739/anti-programmed-cell-death-1-ligand-1-pd-1-pd-l1-antibodies-for-the-treatment-of-urothelial-carcinoma-state-of-the-art-and-future-development
#14
REVIEW
Thomas Powles, Andrea Necchi, Galit Rosen, Subramanian Hariharan, Andrea B Apolo
Immunotherapy with programmed cell death 1/ligand 1 (PD-1/PD-L1) checkpoint inhibitors has expanded a previously limited pool of effective treatment options for patients with metastatic urothelial carcinoma, particularly those with recurring or refractory disease and those who are ineligible for cisplatin. This review reports key findings from completed and ongoing clinical trials that highlight the potential of PD-1/PD-L1 blockade in urothelial carcinoma. A literature search was performed of PubMed, Embase, ClinicalTrials...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29318609/the-efficacy-and-safety-of-anti-pd-1-pd-l1-antibodies-combined-with-chemotherapy-or-ctla4-antibody-as-a-first-line-treatment-for-advanced-lung-cancer
#15
Xiaoling Xu, Zhiyu Huang, Lei Zheng, Yun Fan
Checkpoint inhibitors show promising efficacy in advanced lung cancer, especially in non-small cell lung cancer. This meta-analysis was conducted to explore the therapeutic efficacy and safety of anti-PD-1/PD-L1 antibodies combined with chemotherapy or CTLA4 antibody as first-line treatments for patients with advanced lung cancer. A systematic search was performed in databases for this system review and quantitative meta-analysis. Twelve trials were finally enrolled in the meta-analysis. Our analyses revealed that the combined overall response rate (ORR) and disease control rate (DCR) for immune checkpoint inhibitors combined with chemotherapy for the treatment of non-small cell lung cancer (NSCLC) were 47...
January 10, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#16
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313208/perspective-on-immune-oncology-with-liquid-biopsy-peripheral-blood-mononuclear-cells-and-microbiome-with-non-invasive-biomarkers-in-cancer-patients
#17
REVIEW
A Mitsuhashi, Y Okuma
Antibodies against immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) play a key role in the treatment of advanced lung cancer. To examine the clinical benefits of these agents, preclinical and clinical studies have been conducted to identify definitive biomarkers associated with cancer status. Analysis of the blood and feces of tumor patients has attracted attention in recent studies attempting to identify non-invasive biomarkers such as cytokines, soluble PD-L1, peripheral blood mononuclear cells, and gut microbiota...
January 8, 2018: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29309540/radiotherapy-and-anti-pd-1-pd-l1-combinations-in-lung-cancer-building-better-translational-research-platforms
#18
T Kordbacheh, J Honeychurch, F Blackhall, C Faivre-Finn, T Illidge
Despite the unheralded success of immune checkpoint blockade in delivering durable responses for some patients with non-small cell lung cancer (NSCLC), the majority of patients do not respond. PD-L1 tumour expression and pre-existing tumour T-cell infiltration have been correlated with improved clinical outcomes to anti-PD-1/anti-PD-L1. However, patients with tumours that are negative for PD-L1 expression can also respond to treatment. Strategies to combine other treatment modalities like radiotherapy with immune checkpoint inhibitors are being investigated as means of improving the response rates to PD-1/PD-L1 antibody blockade...
December 22, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29309059/high-dimensional-single-cell-analysis-predicts-response-to-anti-pd-1-immunotherapy
#19
Carsten Krieg, Malgorzata Nowicka, Silvia Guglietta, Sabrina Schindler, Felix J Hartmann, Lukas M Weber, Reinhard Dummer, Mark D Robinson, Mitchell P Levesque, Burkhard Becher
Immune-checkpoint blockade has revolutionized cancer therapy. In particular, inhibition of programmed cell death protein 1 (PD-1) has been found to be effective for the treatment of metastatic melanoma and other cancers. Despite a dramatic increase in progression-free survival, a large proportion of patients do not show durable responses. Therefore, predictive biomarkers of a clinical response are urgently needed. Here we used high-dimensional single-cell mass cytometry and a bioinformatics pipeline for the in-depth characterization of the immune cell subsets in the peripheral blood of patients with stage IV melanoma before and after 12 weeks of anti-PD-1 immunotherapy...
January 8, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29308304/pd-1-related-transcriptome-profile-and-clinical-outcome-in-diffuse-gliomas
#20
Shuai Liu, Zheng Wang, Yinyan Wang, Xing Fan, Chuanbao Zhang, Wenbin Ma, Xiaoguang Qiu, Tao Jiang
Background: PD-1 plays a critical part in control of immune response to malignancy. Anti-PD-1 treatment is a hopeful strategy to improve the dismal prognosis of gliomas. To characterize the role of PD-1 in diffuse gliomas, we investigated its related biological process at transcriptome level and its clinical prognostic value. Method and patients: Through Chinese Glioma Genome Atlas and TCGA datasets, we systematically reviewed a total of 994 cases with RNA-seq data and analyzed the functional annotation of PD-1 by Gene ontology (GO) analysis...
2018: Oncoimmunology
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