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https://www.readbyqxmd.com/read/29757416/early-changes-in-cd4-t-cell-activation-following-blood-stage-plasmodium-falciparum-infection
#1
Chelsea L Edwards, Susanna S Ng, Dillon Corvino, Marcela Montes de Oca, Fabian de Labastida Rivera, Katia Nones, Vanessa Lakis, Nicola Waddell, Fiona H Amante, James S McCarthy, Christian R Engwerda
We examined transcriptional changes in CD4+ T cells during blood-stage Plasmodium falciparum infection in individuals without a history of previous parasite exposure. CD4+ T cell CXCL8 gene (encoding IL-8) transcription was identified as an early biomarker of sub-microscopic P. falciparum infection, with predictive power for parasite growth. Following anti-parasitic drug treatment, a CD4+ T cell regulatory phenotype developed. PD1 expression on CD49b+ CD4+ T (putative type I regulatory (Tr1)) cells after drug treatment negatively correlated with earlier parasite growth...
May 11, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29679564/frequencies-and-expression-levels-of-programmed-death-ligand-1-pd-l1-in-circulating-tumor-rna-ctrna-in-various-cancer-types
#2
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzales, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
April 27, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29645384/liquid-biopsy-zur-%C3%A3-berwachung-von-melanompatienten
#3
REVIEW
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
In den letzten sechs Jahren wurden verschiedene innovative systemische Therapien zur Behandlung des metastasierten malignen Melanoms (MM) entwickelt. Die konventionelle Chemotherapie wurde durch neuartige Primärtherapien abgelöst, darunter systemische Immuntherapien (Anti-CTLA4- und Anti-PD1-Antikörper; Zulassung von Anti-PDL1-Antikörpern erwartet) und Therapien, die gegen bestimmte Mutationen gerichtet sind (BRAF, NRAS und c-KIT). Daher stehen die behandelnden Ärzte neuen Herausforderungen gegenüber, beispielsweise der Stratifizierung von Patienten für geeignete Behandlungen und der Überwachung von Langzeit-Respondern auf Progression...
April 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29575535/inhibition-of-yes-associated-protein-down-regulates-pd-l1-cd274-expression-in-human-malignant-pleural-mesothelioma
#4
Ping-Chih Hsu, Jinbai Miao, Yu-Cheng Wang, Wen-Qian Zhang, Yi-Lin Yang, Chih-Wei Wang, Cheng-Ta Yang, Zhen Huang, Joanna You, Zhidong Xu, David M Jablons, Liang You
Although tumour PD-L1 (CD274) expression had been used as a predictive biomarker in checkpoint immunotherapy targeting the PD1/PD-L1 axis in various cancers, the regulation of PD-L1 (CD274) expression is unclear. Yes-associated protein (YAP), an important oncogenic protein in Hippo signalling pathway, reportedly promotes cancer development. We investigated whether inhibition of YAP down-regulates PD-L1 (CD274) in human malignant pleural mesothelioma (MPM). Western blotting showed that 2 human MPM cell lines (H2052 and 211H) had increased PD-L1 protein expression compared to H290, MS-1 and H28 cells...
March 24, 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29534331/two-independent-studies-show-blood-follicular-t-cell-subsets-allow-the-stratification-of-sj%C3%A3-gren-s-syndrome-patients
#5
Valter R Fonseca, Vasco C Romão, Ana Agua-Doce, João Eurico Fonseca, Luis Graca
We are excited to find that most of our conclusions (1) were replicated in an independent larger primary Sjögren's syndrome (pSS) cohort, as reported by Verstappen et al in their Letter (Verstappen G et al, Arthritis & Rheumatology, in press). Indeed, our colleagues were also able to demonstrate that the ratio of blood T follicular regulatory (Tfr) / T follicular helper (Tfh) cells were increased in pSS patients, and specifically within pSS patients with focus score (FS) ≥ 1, supporting its discriminative value for the diagnosis of pSS...
March 13, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29532035/immune-evasion-mediated-by-pd-l1-on-glioblastoma-derived-extracellular-vesicles
#6
Franz L Ricklefs, Quazim Alayo, Harald Krenzlin, Ahmad B Mahmoud, Maria C Speranza, Hiroshi Nakashima, Josie L Hayes, Kyungheon Lee, Leonora Balaj, Carmela Passaro, Arun K Rooj, Susanne Krasemann, Bob S Carter, Clark C Chen, Tyler Steed, Jeffrey Treiber, Scott Rodig, Katherine Yang, Ichiro Nakano, Hakho Lee, Ralph Weissleder, Xandra O Breakefield, Jakub Godlewski, Manfred Westphal, Katrin Lamszus, Gordon J Freeman, Agnieszka Bronisz, Sean E Lawler, E Antonio Chiocca
Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role...
March 2018: Science Advances
https://www.readbyqxmd.com/read/29512873/liquid-biopsy-to-monitor-melanoma-patients
#7
REVIEW
Maria Rita Gaiser, Nikolas von Bubnoff, Christoffer Gebhardt, Jochen Sven Utikal
During the last six years, several innovative, systemic therapies for the treatment of metastatic malignant melanoma (MM) have emerged. Conventional chemotherapy has been superseded by novel first-line therapies, including systemic immunotherapies (anti-CTLA4 and anti-PD1; authorization of anti-PDL1 is anticipated) and therapies targeting specific mutations (BRAF, NRAS, and c-KIT). Thus, treating physicians are confronted with new challenges, such as stratifying patients for appropriate treatments and monitoring long-term responders for progression...
April 2018: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/29501787/genomics-and-emerging-biomarkers-for-immunotherapy-of-colorectal-cancer
#8
REVIEW
Jakob Nikolas Kather, Niels Halama, Dirk Jaeger
Colorectal cancer (CRC) is a common and lethal disease with a high therapeutic need. For most patients with metastatic CRC, chemotherapy is the only viable option. Currently, immunotherapy is restricted to the particular genetic subgroup of mismatch-repair deficient (MMRd)/microsatellite instable (MSI) CRC. Anti-PD1 therapy was recently FDA-approved as a second-line treatment in this subgroup. However, in a metastatic setting, these MMRd/MSI tumors are vastly outnumbered by mismatch-repair proficient (MMRp)/microsatellite stable (MSS) tumors...
March 1, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29489025/expression-of-pd-l1-indoleamine-2-3-dioxygenase-and-the-immune-microenvironment-in-gastric-adenocarcinoma
#9
Pallavi A Patil, Andrew M Blakely, Kara A Lombardo, Jason T Machan, Thomas J Miner, Li-Juan Wang, Alexander S Marwaha, Andres Matoso
AIMS: The tumour microenvironment is increasingly important in several tumours. We studied the relationship of key players of immune microenvironment with clinicopathological parameters in gastric adenocarcinomas. METHODS AND RESULTS: Tissue microarrays were constructed from gastrectomy specimens, 2004-13. Immunohistochemistry was performed for programmed cell death ligand 1 (PD-L1), indoleamine 2,3-dioxygenase (IDO), tryptophanyl-tRNA synthetase (WARS), guanylate-binding protein 5 (GBP5), tumour-infiltrating lymphocytes (TIL) expressing CD3/CD8/FoxP3/PD1 and mismatch repair proteins (MMRs) MLH1, PMS2, MSH2 and MSH6...
February 28, 2018: Histopathology
https://www.readbyqxmd.com/read/29423108/cancer-immunogenomic-approach-to-neoantigen-discovery-in-a-checkpoint-blockade-responsive-murine-model-of-oral-cavity-squamous-cell-carcinoma
#10
Paul Zolkind, Dariusz Przybylski, Nemanja Marjanovic, Lan Nguyen, Tianxiang Lin, Tanner Johanns, Anton Alexandrov, Liye Zhou, Clint T Allen, Alexander P Miceli, Robert D Schreiber, Maxim Artyomov, Gavin P Dunn, Ravindra Uppaluri
Head and neck squamous cell carcinomas (HNSCC) are an ideal immunotherapy target due to their high mutation burden and frequent infiltration with lymphocytes. Preclinical models to investigate targeted and combination therapies as well as defining biomarkers to guide treatment represent an important need in the field. Immunogenomics approaches have illuminated the role of mutation-derived tumor neoantigens as potential biomarkers of response to checkpoint blockade as well as representing therapeutic vaccines...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29405038/systemic-treatments-for-metastatic-cutaneous-melanoma
#11
REVIEW
Sandro Pasquali, Andreas V Hadjinicolaou, Vanna Chiarion Sileni, Carlo Riccardo Rossi, Simone Mocellin
BACKGROUND: The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000. OBJECTIVES: To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma...
February 6, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29399387/analysis-of-pd1-pdl1-pdl2-expression-and-t-cells-infiltration-in-1014-gastric-cancer-patients
#12
Xiaofang Xing, Jianping Guo, Xianzi Wen, Guangyu Ding, Bo Li, Bin Dong, Qin Feng, Shen Li, Jian Zhang, Xiaojing Cheng, Ting Guo, Hong Du, Ying Hu, Xiaohong Wang, Lin Li, Qingda Li, Meng Xie, Liting Li, Xiangyu Gao, Fei Shan, Ziyu Li, Xiaomin Ying, Tao Zhou, Jiping Wang, Jiafu Ji
Although immune checkpoint blockade have demonstrated promising results, their effects on gastric cancer (GC) are under investigation. Understanding the clinical significance of PD1 and its ligands' expression, together with T cell infiltration might provide clues for biomarkers screening in GC immunotherapy. Immunohistochemistry were performed on a tissue microarray including 1,014 GC specimens using PD1, PDL1 and PDL2 antibodies. T cell markers CD3 and CD8 were also stained and quantified by automated image analysis...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29391205/primary-and-metastatic-brain-cancer-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatment
#13
REVIEW
F Passiglia, C Caglevic, E Giovannetti, J A Pinto, P Manca, S Taverna, A Listì, I Gil-Bazo, L E Raez, A Russo, C Rolfo
Recent studies with immunomodulatory agents targeting both cytotoxic T-lymphocyte protein 4 (CTLA4) and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PDL1) have shown to be very effective in several cancers revealing an unexpected great activity in patients with both primary and metastatic brain tumors. Combining anti-CTLA4 and anti-PD1 agents as upfront systemic therapy has revealed to further increase the clinical benefit observed with single agent, even at cost of higher toxicity. Since the brain is an immunological specialized area it's crucial to establish the specific composition of the brain tumors' microenvironment in order to predict the potential activity of immunomodulatory agents...
January 31, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29388007/the-role-of-tumor-infiltrating-lymphocytes-tils-as-a-predictive-biomarker-of-response-to-anti-pd1-therapy-in-patients-with-metastatic-non-small-cell-lung-cancer-or-metastatic-melanoma
#14
Anton Uryvaev, Maria Passhak, Dov Hershkovits, Edmond Sabo, Gil Bar-Sela
Immunotherapy plays an important role in cancer treatment. Biomarkers that can predict response, including tumor-infiltrating lymphocytes (TILs), are in the spotlight of many studies. This cohort study was designed to evaluate the role of CD4+ and CD8+ TILs as predictive factors for response to anti PD-1 treatment in patients with metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma. We evaluated the expression of CD4+ and CD8+ TILs in tissue samples of 56 patients with metastatic NSCLC or melanoma treated with anti-PD1 immunotherapy...
January 31, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29363363/nivolumab-for-the-treatment-of-urothelial-cancers
#15
Min Yuen Teo, Jonathan E Rosenberg
Advanced urothelial cancer patients had limited therapeutic options following failure of platinum-based chemotherapy. The recognition that anti-PD1/PDL1 immune checkpoint inhibitors lead to dramatic and durable responses in a subset of patients has transformed the therapeutic landscape of these cancers. Since May 2016, five agents targeting this pathway have been approved by the US FDA, including the PD-1 inhibitor nivolumab. Areas covered: The purpose of this paper was to review the safety, activity and efficacy of nivolumab, an anti-PD1 checkpoint inhibitor for the treatment of locally-advanced or metastatic urothelial cancers...
March 2018: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/29360924/neopepsee-accurate-genome-level-prediction-of-neoantigens-by-harnessing-sequence-and-amino-acid-immunogenicity-information
#16
S Kim, H S Kim, E Kim, M G Lee, E Shin, S Paik, S Kim
Background: Tumor-specific mutations form novel immunogenic peptides called neoantigens. Neoantigens can be used as a biomarker predicting patient response to cancer immunotherapy. Although a predicted binding affinity (IC50) between peptide and major histocompatibility complex class I (MHC-I) is currently used for neoantigen prediction, large number of false-positives exist. Materials and methods: We developed Neopepsee, a machine learning-based neoantigen prediction program for next-generation sequencing data...
January 19, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29355614/head-and-neck-squamous-cell-carcinoma-genomics-and-emerging-biomarkers-for-immunomodulatory-cancer-treatments
#17
REVIEW
Benjamin Solomon, Richard J Young, Danny Rischin
Head and neck squamous cell carcinoma (HNSCC) comprises a heterogeneous group of tumors that arise from the squamous epithelium of the oral cavity, oropharynx, larynx and hypopharynx. While many HNSCCs are related to classical etiologic factors of smoking and alcohol, a clinically, genomically, and immunologically distinct subgroup of tumors arise from the epithelium of the tonsil and the base of tongue as a result of infection with Human Papilloma Virus (HPV). In this review we describe the genomic and immunologic landscape of HNSCC, highlighting differences between HPV-positive and HPV-negative HNSCC...
January 30, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29327065/blood-predictive-biomarkers-for-nivolumab-in-advanced-melanoma
#18
Edouard Chasseuil, Mélanie Saint-Jean, Hannah Chasseuil, Lucie Peuvrel, Gaëlle Quéreux, Jean-Michel Nguyen, Aurélie Gaultier, Emilie Varey, Amir Khammari, Brigitte Dréno
Nivolumab response rate is 40% in metastatic melanoma. Few studies have evaluated pre-treatment biomarkers predictive of response. The aim of this study was to identify potential peripheral blood biomarkers associated with survival in patients with advanced melanoma treated with nivolumab. All advanced melanoma cases treated with anti-programmed cell death protein 1 (anti-PD1) over a 3-year period in the Dermato-Oncology Department, Nantes, France were identified. For each case, 9 potential blood biomarkers were identified...
December 20, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/29227333/illustrative-cases-for-monitoring-by-quantitative-analysis-of-braf-nras-ctdna-mutations-in-liquid-biopsies-of-metastatic-melanoma-patients-who-gained-clinical-benefits-from-anti-pd1-antibody-therapy
#19
Teofila Seremet, Simon Planken, Max Schreuer, Yanina Jansen, Mélanie Delaunoy, Hakim El Housni, Danielle Lienard, Véronique Del Marmol, Pierre Heimann, Bart Neyns
Anti-programmed death 1 (PD-1) monoclonal antibodies improve the survival of metastatic melanoma patients. Predictive or monitoring biomarkers for response to this therapy could improve the clinical management of these patients. To date, no established biomarkers are available for monitoring the response to immunotherapy. Tumor- specific mutations in circulating tumor DNA (ctDNA) such as BRAF and NRAS mutations for melanoma patients have been proposed for monitoring of immunotherapy response. We present seven illustrative cases for the use of ctDNA BRAF and NRAS mutations' monitoring in plasma...
February 2018: Melanoma Research
https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#20
REVIEW
Fabienne Venet, Guillaume Monneret
Sepsis is defined as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis can induce acute kidney injury and multiple organ failures and represents the most common cause of death in the intensive care unit. Sepsis initiates a complex immune response that varies over time, with the concomitant occurrence of both pro-inflammatory and anti-inflammatory mechanisms. As a result, most patients with sepsis rapidly display signs of profound immunosuppression, which is associated with deleterious consequences...
February 2018: Nature Reviews. Nephrology
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