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Cancer and immune

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https://www.readbyqxmd.com/read/29351573/multicenter-french-harmonization-study-for-pd-l1-ihc-testing-in-non-small-cell-lung-cancer
#1
J Adam, N Le Stang, I Rouquette, A Cazes, C Badoual, H Pinot-Roussel, L Tixier, C Danel, F Damiola, D Damotte, F Penault-Llorca, S Lantuéjoul
Background: Various PD-L1 immunohistochemistry (IHC) assays have been developed and used in clinical trials in association with different drugs. In order to harmonize and make PD-L1 testing in non-small cell lung cancer (NSCLC) widely available, we conducted a multicenter study comparing PD-L1 standardized assays and laboratory-developed tests (LDT). Methods: IHC with five anti-PD-L1 monoclonal antibodies (28-8, 22C3, E1L3N, SP142 and SP263) was performed concomitantly on 41 NSCLC surgical specimens in 7 centers using Dako Autostainer Link 48 (3 centers), Leica Bond (2 centers) or Ventana BenchMark Ultra (2 centers), platforms...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351464/vitamin-d-and-regulation-of-vascular-cell-function
#2
Nasim Jamali, Christine M Sorenson, Nader Sheibani
Vitamin D deficiency is linked to pathogenesis of many diseases including cardiovascular, cancer, and various eye diseases. In recent years, important roles for vitamin D in regulation of immune function, inflammation, angiogenesis, and aging have been demonstrated. Thus, vitamin D and its analogs have been evaluated for treatment of various types of cancer and chronic diseases. We previously showed that the active form of vitamin D (1, 25(OH)2D3) is a potent inhibitor of angiogenesis. This activity is consistent with the important role proposed for vitamin D and its analogs in the mitigation of tumor growth through inhibition of angiogenesis...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29350913/environmentally-triggerable-retinoic-acid-inducible-gene-i-agonists-using-synthetic-polymer-overhangs
#3
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna M Pyle, John T Wilson
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities...
January 19, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29350712/vaccination-for-human-papillomavirus-immunization-practices-in-the-u-s-military%C3%A2
#4
Jennifer J Buechel
Human papillomavirus (HPV) is the most common sexually transmitted infection and is a leading etiology for cancer. The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination of males and females aged 11-26 years. Studies suggest that U.S. military service members have higher HPV incidence rates and lower vaccination rates compared to the national average. Although the U.S. military enforces many recommended vaccines, the HPV vaccine fails to make the list. 
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February 1, 2018: Clinical Journal of Oncology Nursing
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#5
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#6
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29350049/targeted-and-off-target-bystander-and-abscopal-effects-of-radiation-therapy-redox-mechanisms-and-risk-benefit-analysis
#7
Jean-Pierre Pouget, Alexandros G Georgakilas, Jean-Luc Ravanat
Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29349927/treatment-related-toxicities-of-immune-checkpoint-inhibitors-in-advanced-cancers-a-meta-analysis
#8
Johnathan Man, Georgia Ritchie, Matthew Links, Sally Lord, Chee Khoon Lee
BACKGROUND: We performed a meta-analysis to quantify toxic death, adverse events (AEs) and treatment discontinuation due to AEs from checkpoint inhibitors (CI). METHODS: We searched for randomized trials with adequate reporting for toxicity outcomes. Pooled risk ratios were estimated for CI versus chemotherapy or different combinations of these agents. RESULTS: Twenty trials of five different cancers with 10 794 patients with performance status 0 or 1 were identified...
January 19, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#9
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29348988/anal-squamous-cell-carcinoma-in-a-patient-with-myasthenia-gravis-is-immunosuppression-the-main-underlying-etiology
#10
Muhammad Masab, Muhammad W Saif
Patients who are immunocompromised by diseases such as human immunodeficiency virus (HIV) infection are more prone to develop some malignancies such as Kaposi's sarcoma and central nervous system (CNS) lymphomas. Historically, anal squamous cell carcinoma (SCC) was also included on the list as an acquired immunodeficiency syndrome (AIDs)-defining cancer.  Similarly, compromised immune disorders including severe immunosuppression, haematologic malignancies, and solid organ transplantation have been identified as important risk factors for the development of anal SCC...
November 15, 2017: Curēus
https://www.readbyqxmd.com/read/29348878/identification-of-cancer-prognosis-associated-functional-modules-using-differential-co-expression-networks
#11
Wenshuai Yu, Shengjie Zhao, Yongcui Wang, Brian Nlong Zhao, Weiling Zhao, Xiaobo Zhou
The rapid accumulation of cancer-related data owing to high-throughput technologies has provided unprecedented choices to understand the progression of cancer and discover functional networks in multiple cancers. Establishment of co-expression networks will help us to discover the systemic properties of carcinogenesis features and regulatory mechanisms of multiple cancers. Here, we proposed a computational workflow to identify differentially co-expressed gene modules across 8 cancer types by using combined gene differential expression analysis methods and a higher-order generalized singular value decomposition...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#12
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348630/expression-of-inflammasome-proteins-and-inflammasome-activation-occurs-in-human-but-not-in-murine-keratinocytes
#13
Jennifer Sand, Eric Haertel, Thomas Biedermann, Emmanuel Contassot, Ernst Reichmann, Lars E French, Sabine Werner, Hans-Dietmar Beer
Inflammasomes are multimeric protein complexes that assemble upon sensing of a variety of stress factors. Their formation results in caspase-1-mediated activation and secretion of the pro-inflammatory cytokines pro-interleukin(IL)-1β and -18, which induce an inflammatory response. Inflammation is supported by a lytic form of cell death, termed pyroptosis. Innate immune cells, such as macrophages or dendritic cells, express and activate inflammasomes. However, it has also been demonstrated that human primary keratinocytes activate different types of inflammasomes in vitro, for example, upon UVB irradiation or viral infection...
January 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29348598/increased-diversity-with-reduced-diversity-evenness-of-tumor-infiltrating-t-cells-for-the-successful-cancer-immunotherapy
#14
Akihiro Hosoi, Kazuyoshi Takeda, Koji Nagaoka, Tamaki Iino, Hirokazu Matsushita, Satoshi Ueha, Shin Aoki, Kouji Matsushima, Masato Kubo, Teppei Morikawa, Kazutaka Kitaura, Ryuji Suzuki, Kazuhiro Kakimi
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348577/targeting-b-cell-receptor-signalling-in-cancer-preclinical-and-clinical-advances
#15
REVIEW
Jan A Burger, Adrian Wiestner
B cell receptor (BCR) signalling is crucial for normal B cell development and adaptive immunity. BCR signalling also supports the survival and growth of malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism of BCR pathway activation in these diseases includes continuous BCR stimulation by microbial antigens or autoantigens present in the tissue microenvironment, activating mutations within the BCR complex or downstream signalling components and ligand-independent tonic BCR signalling...
January 19, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29348572/areca-nut-extracts-mobilize-calcium-and-release-pro-inflammatory-cytokines-from-various-immune-cells
#16
Malika Faouzi, Ram P Neupane, Jian Yang, Philip Williams, Reinhold Penner
Betel nut consumption has significant implications for the public health globally, as the wide-spread habit of Areca chewing throughout Asia and the Pacific is associated with a high prevalence of oral carcinoma and other diseases. Despite a clear causal association of betel nut chewing and oral mucosal diseases, the biological mechanisms that link Areca nut-contained molecules, inflammation and cancer remain underexplored. In this study we show that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various immune cell lines...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348263/phosphoinositide-3-kinase-gamma-inhibition-protects-from-anthracycline-cardiotoxicity-and-reduces-tumor-growth
#17
Mingchuan Li, Valentina Sala, Maria Chiara De Santis, James Cimino, Paola Cappello, Nicola Pianca, Anna Di Bona, Jean Piero Margaria, Miriam Martini, Edoardo Lazzarini, Flora Pirozzi, Luca Rossi, Irene Franco, Julia Bornbaum, Jacqueline Heger, Susanne Rohrbach, Alessia Perino, Carlo G Tocchetti, Braulio H F Lima, Mauro M Teixeira, Paolo E Porporato, Rainer Schulz, Annalisa Angelini, Marco Sandri, Pietro Ameri, Sebastiano Sciarretta, Roberto César P Lima-Júnior, Marco Mongillo, Tania Zaglia, Fulvio Morello, Francesco Novelli, Emilio Hirsch, Alessandra Ghigo
Background -Anthracyclines, such as doxorubicin (DOX), are potent anti-cancer agents for the treatment of solid tumors and hematological malignancies. However, their clinical use is hampered by cardiotoxicity. This study sought to investigate the role of PI3Kγ in DOX-induced cardiotoxicity and the potential cardio-protective and anti-cancer effects of PI3Kγ inhibition. Methods -Mice expressing a kinase-inactive PI3Kγ or receiving PI3Kγ selective inhibitors were subjected to chronic DOX treatment. Cardiac function was analyzed by echocardiography and DOX-mediated signaling was assessed in whole hearts or in isolated cardiomyocytes...
January 18, 2018: Circulation
https://www.readbyqxmd.com/read/29347949/effects-of-surgery-and-anesthetic-choice-on-immunosuppression-and-cancer-recurrence
#18
REVIEW
Ryungsa Kim
BACKGROUND: The relationship between surgery and anesthetic-induced immunosuppression and cancer recurrence remains unresolved. Surgery and anesthesia stimulate the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) to cause immunosuppression through several tumor-derived soluble factors. The potential impact of surgery and anesthesia on cancer recurrence was reviewed to provide guidance for cancer surgical treatment. METHODS: PubMed was searched up to December 31, 2016 using search terms such as, "anesthetic technique and cancer recurrence," "regional anesthesia and cancer recurrence," "local anesthesia and cancer recurrence," "anesthetic technique and immunosuppression," and "anesthetic technique and oncologic surgery...
January 18, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#19
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346528/a-novel-stromal-lncrna-signature-reprograms-fibroblasts-to-promote-the-growth-of-oral-squamous-cell-carcinoma-via-lncrna-caf-interleukin-33
#20
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, Xiaofeng Huang, Qingang Hu, Hui Wang, Yuxian Song, Yanhong Ni, Yayi Hou
Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune cells in the tumor microenvironment (TME). CAFs interact with cancer cells to promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate cell growth, apoptosis, and metastasis of cancer cells, but their role in stromal cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter...
January 13, 2018: Carcinogenesis
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