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pd-1 and cancer

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https://www.readbyqxmd.com/read/28430626/expression-of-pd-l1-and-prognosis-in-breast-cancer-a-meta-analysis
#1
Minghui Zhang, Houbin Sun, Shu Zhao, Yan Wang, Haihong Pu, Yan Wang, Qingyuan Zhang
The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest. However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to assess the association between PD-L1 protein expression and clinicopathological features and the impact of this relationship on breast cancer survival. We performed a systematic search of the PubMed, EMBASE, and Cochrane Library databases to determine the correlations among PD-L1 expression, clinicopathological features and overall survival (OS)...
February 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430587/parkin-regulates-translesion-dna-synthesis-in-response-to-uv-radiation
#2
Xuefei Zhu, Xiaolu Ma, Yingfeng Tu, Min Huang, Hongmei Liu, Fengli Wang, Juanjuan Gong, Jiuqiang Wang, Xiaoling Li, Qian Chen, Hongyan Shen, Shu Zhu, Yun Wang, Yang Liu, Caixia Guo, Tie-Shan Tang
Deficiency of Parkin is a major cause of early-onset Parkinson's disease (PD). Notably, PD patients also exhibit a significantly higher risk in melanoma and other skin tumors, while the mechanism remains largely unknown. In this study, we show that depletion of Parkin causes compromised cell viability and genome stability after ultraviolet (UV) radiation. We demonstrate that Parkin promotes efficient Rad18-dependent proliferating cell nuclear antigen (PCNA) monoubiquitination by facilitating the formation of Replication protein A (RPA)-coated ssDNA upon UV radiation...
April 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#3
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28428879/a-systems-biology-approach-to-investigating-the-influence-of-exercise-and-fitness-on-the-composition-of-leukocytes-in-peripheral-blood
#4
Michael P Gustafson, Ara Celi DiCostanzo, Courtney M Wheatley, Chul-Ho Kim, Svetlana Bornschlegl, Dennis A Gastineau, Bruce D Johnson, Allan B Dietz
BACKGROUND: Exercise immunology has become a growing field in the past 20 years, with an emphasis on understanding how different forms of exercise affect immune function. Mechanistic studies are beginning to shed light on how exercise may impair the development of cancer or be used to augment cancer treatment. The beneficial effects of exercise on the immune system may be exploited to improve patient responses to cancer immunotherapy. METHODS: We investigated the effects of acute exercise on the composition of peripheral blood leukocytes over time in a male population of varying fitness...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428785/interferon-gamma-induces-changes-in-natural-killer-nk-cell-ligand-expression-and-alters-nk-cell-mediated-lysis-of-pediatric-cancer-cell-lines
#5
Arianexys Aquino-López, Vladimir V Senyukov, Zlatko Vlasic, Eugenie S Kleinerman, Dean A Lee
Natural killer (NK) cells have therapeutic potential for cancer due to their capacity for targeting tumor cells without prior sensitization. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion that secret 20 times the amount of interferon gamma (IFNγ) than resting NK cells. IFNγ can upregulate major histocompatibility complex (MHC)-class I, an inhibitory ligand for NK cells, but can also upregulate intercellular adhesion molecule 1 (ICAM-1) which promotes NK:target cell interaction for an efficient lysis...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28427522/the-role-of-anti-pd-1-and-anti-pd-l1-agents-in-the-treatment-of-diffuse-large-b-cell-lymphoma-the-future-is-now
#6
REVIEW
Luis Miguel Juárez-Salcedo, Jose Sandoval-Sus, Lubomir Sokol, Julio C Chavez, Samir Dalia
Immune checkpoints inhibitors have been incorporated into standard treatment protocols for advanced solid tumors. The aim of T-cell-based immune therapy in cancer has been to generate durable clinical benefits for patients, paired with enhanced side effect profiles. The beneficial antitumoral activity of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has been thoroughly demonstrated in certain metastatic malignancies (e.g. melanoma, non-small cell lung cancer, renal cell carcinoma); however, the therapeutic role in lymphoid cancers is complex...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28427226/microrna-152-regulates-immune-response-via-targeting-b7-h1-in-gastric-carcinoma
#7
Yaxin Wang, Di Wang, Gengchen Xie, Yuping Yin, Ende Zhao, Kaixiong Tao, Ruidong Li
MiR-152 has been reported may be involved in carcinogenesis in gastric cancer. However, its role has not been comprehensively investigated in gastric cancer. We found miR-152 in human gastric cancer tissues were significantly lower than that in matched adjacent normal tissues. Meanwhile, lower miR-152 was also found in gastric cancer cell lines. The stage, tumor size and lymph node metastasis rate were significant higher in low-miR-152 group in clinical patients. Furthermore, there was a marked correlation between the levels of miR-152 and B7-H1 mRNA in gastric cancer tissues...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423520/prognostic-role-of-programmed-death-ligand-1-pd-l1-expressing-tumor-infiltrating-lymphocytes-in-testicular-germ-cell-tumors
#8
Michal Chovanec, Zuzana Cierna, Viera Miskovska, Katarina Machalekova, Daniela Svetlovska, Katarina Kalavska, Katarina Rejlekova, Stanislav Spanik, Karol Kajo, Pavel Babal, Jozef Mardiak, Michal Mego
PURPOSE: Testicular germ cell tumors (TGCTs) are nearly universally curable malignancies. Nevertheless, standard cisplatin-based chemotherapy is not curative in a small subgroup of patients. Previously, we showed that PD-L1 overexpression is associated with worse prognosis in TGCTs, while tumor infiltrating lymphocytes (TILs) are prognostic in different types of cancer. This study aimed to evaluate the prognostic value of PD-1 and PD-L1 expressing TILs in TGCTs. RESULTS: PD-L1 positive TILs were found significantly more often in seminomas (95...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421161/incidence-of-immune-related-adverse-events-with-program-death-receptor-1-and-program-death-receptor-1-ligand-directed-therapies-in-genitourinary-cancers
#9
REVIEW
Benjamin L Maughan, Erin Bailey, David M Gill, Neeraj Agarwal
Program death receptor-1 (PD-1) and program death receptor-1 ligand (PD-L1) inhibitors are increasingly being used in the clinic to treat a growing number of malignancies, including many genitourinary (GU) malignancies. These immune-based therapies have demonstrated a distinct toxicity profile compared to traditional chemotherapy and the targeted therapies directed at the vascular endothelial growth factor pathway or the mammalian target of rapamycin pathway. Autoimmune toxicity targeting the skin, gastrointestinal tract, or the endocrine organs are some of the more common adverse events (AEs) noted with these therapies...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28420726/intra-and-inter-observer-reproducibility-assessment-of-pd-l1-biomarker-in-non-small-cell-lung-cancer-nsclc
#10
Wendy A Cooper, Prudence A Russell, Maya Cherian, Edwina E Duhig, David Godbolt, Peter J Jessup, Christine Khoo, Connull Leslie, Annabelle Mahar, David F Moffat, Vanathi Sivasubramaniam, Céline Faure, Alena Reznichenko, Amanda Grattan, Stephen B Fox
<br />Reliable and reproducible methods for identifying PD-L1 expression on tumor cells are necessary to identify responders to anti-PD-1 therapy. We tested the reproducibility of the assessment of PD-L1 expression in non-small cell lung cancer (NSCLC) tissue samples by pathologists.<br />Experimental Design: <br />NSCLC samples were stained with PD-L1 22C3 pharmDx™ kit using the Dako Autostainer Link 48 Platform. Two sample sets of 60 samples each were designed to assess inter- and intra-observer reproducibility considering 2 cut-points for positivity: 1% or 50% of PD-L1 stained tumor cells...
April 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28420421/analysis-of-100-000-human-cancer-genomes-reveals-the-landscape-of-tumor-mutational-burden
#11
Zachary R Chalmers, Caitlin F Connelly, David Fabrizio, Laurie Gay, Siraj M Ali, Riley Ennis, Alexa Schrock, Brittany Campbell, Adam Shlien, Juliann Chmielecki, Franklin Huang, Yuting He, James Sun, Uri Tabori, Mark Kennedy, Daniel S Lieber, Steven Roels, Jared White, Geoffrey A Otto, Jeffrey S Ross, Levi Garraway, Vincent A Miller, Phillip J Stephens, Garrett M Frampton
BACKGROUND: High tumor mutational burden (TMB) is an emerging biomarker of sensitivity to immune checkpoint inhibitors and has been shown to be more significantly associated with response to PD-1 and PD-L1 blockade immunotherapy than PD-1 or PD-L1 expression, as measured by immunohistochemistry (IHC). The distribution of TMB and the subset of patients with high TMB has not been well characterized in the majority of cancer types. METHODS: In this study, we compare TMB measured by a targeted comprehensive genomic profiling (CGP) assay to TMB measured by exome sequencing and simulate the expected variance in TMB when sequencing less than the whole exome...
April 19, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28419570/oral-lichenoid-reactions-associated-with-anti-pd-1-pd-l1-therapies-clinicopathological-findings
#12
V Sibaud, C Eid, V R Belum, P Combemale, B Barres, L Lamant, L Mourey, C Gomez-Roca, C L Estilo, R Motzer, E Vigarios, Mario E Lacouture
Immune checkpoint inhibitors targeting the programmed cell death receptor-1 (PD-1) or its ligand (PD-L1) show broad activity across different tumor types and currently represent one of the keystones of cancer management. Dermatologic toxicities are one of the most frequent immune-related adverse events (irAEs) induced by these new monoclonal antibodies. Maculopapular rash, pruritus, exacerbation of psoriasis or more specific autoimmune disorders (e.g. vitiligo, alopecia areata, and bullous pemphigoid) are amongst the most commonly reported AEs...
April 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/28419539/pd-l1-expression-in-extrahepatic-cholangiocarcinoma
#13
Dirk Walter, Eva Herrmann, Andreas Schnitzbauer, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag, Sylvia Hartmann
AIMS: To investigate expression of programmed cell death 1 (PD-1) receptor / programmed cell death ligand 1 (PD-L1) pathway as well as clinicopathological characteristics in extrahepatic cholangiocarcinoma (eCCA). METHODS: Tissue samples from patients with eCCA (n=69; perihilar CCA=40, distal CCA=29), who underwent surgical resection in the period from 2007 to 2015 were evaluated for PD-1, PD-L1, CD3 and CD163 expression and correlation with clinicopathological characteristics, including survival data, was performed...
April 17, 2017: Histopathology
https://www.readbyqxmd.com/read/28418920/complementary-utility-of-targeted-next-generation-sequencing-and-immunohistochemistry-panels-as-a-screening-platform-to-select-targeted-therapy-for-advanced-gastric-cancer
#14
Hyo Song Kim, Hanna Lee, Su-Jin Shin, Seung-Hoon Beom, Minkyu Jung, Sujin Bae, Eun Young Lee, Kyu Hyun Park, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Yong Chan Lee, Woong Sub Koom, Joon Seok Lim, Hyun Cheol Chung, Sung Hoon Noh, Sun Young Rha, Hyunki Kim, Soonmyung Paik
We tested the clinical utility of combined profiling of Ion Torrent PGM based next-generation sequencing (NGS) and immunohistochemistry (IHC) for assignment to molecularly targeted therapies. A consecutive cohort of 93 patients with advanced/metastatic GC who underwent palliative chemotherapy between March and December 2015 were prospectively enrolled. Formalin fixed paraffin embedded tumor biopsy specimens were subjected to a 10 GC panels [Epstein Barr virus encoding RNA in-situ hybridization, IHC for mismatch repair proteins (MMR; MLH1, PMS2, MSH2, and MSH6), receptor tyrosine kinases (HER2, EGFR, and MET), PTEN, and p53 protein], and a commercial targeted NGS panel of 52 genes (Oncomine Focus Assay)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418918/the-pd-1-pd-l1-expression-and-cd3-t-cell-infiltration-in-relation-to-outcome-in-advanced-gastric-signet-ring-cell-carcinoma-representing-a-potential-biomarker-for-immunotherapy
#15
Shenying Jin, Bo Xu, Lixia Yu, Yao Fu, Hongyan Wu, Xiangshan Fan, Jia Wei, Baorui Liu
Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1(PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in 89 advanced SRCC patients...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418281/programmed-death-ligand-1-pd-l1-expression-in-the-programmed-death-receptor-1-pd-1-pd-l1-blockade-a-key-player-against-various-cancers
#16
Jian Guan, Khin Sandar Lim, Tarek Mekhail, Chung-Che Chang
CONTEXT: - Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy. OBJECTIVE: - To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression...
April 18, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/28418082/non-digestible-carbohydrates-supplementation-increases-mir-32-expression-in-the-healthy-human-colorectal-epithelium-a-randomized-controlled-trial
#17
Fiona C Malcomson, Naomi D Willis, Iain McCallum, Long Xie, Bart Lagerwaard, Seamus Kelly, Michael Bradburn, Nigel J Belshaw, Ian T Johnson, John C Mathers
Colorectal cancer (CRC) risk is modulated by diet and there is convincing evidence of reduced risk with higher non-digestible carbohydrates (NDCs) consumption. Resistant starch (RS), a NDC, positively modulates the expression of oncogenic microRNAs, suggesting that this could be a mechanism through which NDCs protect against CRC. The present study aimed to investigate the effects of supplementation with two NDCs, RS and polydextrose (PD), on microRNA expression in the macroscopically-normal human rectal epithelium using samples from the DISC Study, a randomised, double-blind, placebo-controlled dietary intervention...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28417343/adjuvant-therapy-for-melanoma
#18
REVIEW
Aya Agha, Ahmad A Tarhini
Systemic adjuvant therapy for surgically resected cutaneous melanoma that is at high risk for disease recurrence and death targets residual micrometastatic disease which is the source of future local or distant relapse. Interferon-alfa (IFNα) has been the most extensively studied in regimens that varied by dosage, route of administration, formulation, and duration of therapy. Most regimens have demonstrated improvements in relapse-free survival (RFS), while the regimen administered at high dosage (HDI) showed improvements in overall survival (OS) in two out of three RCTs...
May 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28416578/quantitative-mass-spectrometry-analysis-of-pd-l1-protein-expression-n-glycosylation-and-expression-stoichiometry-with-pd-1-and-pd-l2-in-human-melanoma
#19
Carlos A Morales-Betanzos, Hyoungjoo Lee, Paula I Gonzalez-Ericsson, Justin M Balko, Douglas B Johnson, Lisa J Zimmerman, Daniel C Liebler
Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted mass spectrometry (MS) platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from approximately 0.03 to 1.5 fmol/microgram protein and the PRM data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody...
April 17, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28416123/immune-checkpoint-inhibitors-for-patients-with-advanced-non-small-cell-lung-cancer-a%C3%A2-systematic-review
#20
REVIEW
Peter M Ellis, Emily T Vella, Yee C Ung
Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC...
February 16, 2017: Clinical Lung Cancer
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