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https://www.readbyqxmd.com/read/29241546/neutrophils-and-snail-orchestrate-the-establishment-of-a-pro-tumor-microenvironment-in-lung-cancer
#1
Julien Faget, Svenja Groeneveld, Gael Boivin, Martial Sankar, Nadine Zangger, Miguel Garcia, Nicolas Guex, Inti Zlobec, Loïc Steiner, Alessandra Piersigilli, Ioannis Xenarios, Etienne Meylan
Understanding the immune compartment of tumors facilitates the development of revolutionary new therapies. We used a Kras(G12D)-driven mouse model of lung cancer to establish an immune signature and identified a contribution of Gr1+ neutrophils to disease progression. Depletion experiments showed that Gr1+ cells (1) favor tumor growth, (2) reduce T cell homing and prevent successful anti-PD1 immunotherapy, and (3) alter angiogenesis, leading to hypoxia and sustained Snail expression in lung cancer cells. In turn, Snail accelerated disease progression and increased intratumoral Cxcl2 secretion and neutrophil infiltration...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29241019/quantitative-analysis-of-a-multiplexed-immunofluorescence-panel-in-t-cell-lymphoma
#2
Siok-Bian Ng, Shuangyi Fan, Shoa-Nian Choo, Michal Hoppe, Hoang Mai Phuong, Sanjay De Mel, Anand D Jeyasekharan
Immunohistochemistry (IHC) provides clinically useful information on protein expression in cancer cells. However, quantification of colocalizing signals using conventional IHC and visual scores is challenging. Here we describe the application of quantitative immunofluorescence in angioimmunoblastic T-cell lymphoma (AITL), a peripheral T-cell lymphoma characterized by cellular heterogeneity that impedes IHC interpretation and quantification. A multiplexed immunofluorescence (IF) panel comprising T- and B-lymphocyte markers along with T-follicular helper (TFH) markers was validated for appropriate cellular localization in sections of benign tonsillar tissue and tested in two samples of AITL, using a Vectra microscope for spectral imaging and InForm software for analysis...
December 1, 2017: SLAS Technology
https://www.readbyqxmd.com/read/29239195/-immunotherapy-of-colorectal-and-anal-carcinoma
#3
J Tomášek, I Kiss
BACKGROUND: The lower part of the digestive tract includes the large intestine, rectum and anus. Treatment algorithms of cancers in these localities have significant differences in both early and advanced stages. The vast majority of metastatic cases are incurable. A few years ago, it was generally accepted that gastrointestinal tumors are poorly immunogenic and modern immunotherapy would not work in gastrointestinal cancers. The breakthrough has become the recognition of the mismatch repair system (MMR) that affects the microsatellite instability (MSI) and its role in the development of colorectal carcinoma (CRC)...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29239193/-checkpoint-inhibitors-in-the-treatment-of-upper-gastrointestinal-tract-tumors
#4
R Obermannova
Chemotherapy prolongs overall survival (OS) in esophageal (EC) and gastric cancer (GC). Unsatisfactory results of systemic therapy initiated a search for new treatment options. In metastatic disease, a number of targeted drugs were tested; however, several phase III studies assessing receptor tyrosin kinase-related signaling pathways, such as EGFR, MET/HGF or mTOR, failed. Trastuzumab remains the only targeted drug with a known molecular predictor, which extended the OS in metastatic gastric adenocarcinoma and adenocarcinoma of esophago-gastric junction...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/29228696/mp0250-a-vegf-and-hgf-neutralizing-darpin%C3%A2-molecule-shows-high-anti-tumor-efficacy-in-mouse-xenograft-and-patient-derived-tumor-models
#5
Ulrike Fiedler, Savira Ekawardhani, Andreas Cornelius, Pat Gilboy, Talitha R Bakker, Ignacio Dolado, Michael T Stumpp, Keith M Dawson
Background: The VEGF/VEGFR and the HGF/cMET pathways are key mediators of the interplay of tumor cells and their microenvironment. However, inhibition of VEGF has been shown to produce only limited clinical benefit and inhibition of the activation of cMET by HGF has not translated into clinical benefit in pivotal trials. MP0250, a DARPin® molecule that specifically inhibits both VEGF and HGF has been developed to explore the clinical potential of dual inhibition of these pathways. Results: MP0250 binding to VEGF and HGF inhibited downstream signalling through VEGFR2 and cMET resulting in inhibition of proliferation of VEGF- and HGF-dependent cells...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29228559/initial-experience-of-anti-pd1-therapy-with-nivolumab-in-advanced-hepatocellular-carcinoma
#6
Duan Feng, Xie Hui, Lu Shi-Chun, Bai Yan-Hua, Cui Li, Li Xiao-Hui, Yan Jie-Yu
Purpose: To evaluate efficacy and safety of anti-PD1 therapy with nivolumab for treatment of advanced hepatocellular carcinoma (HCC). Methods: From Jan 2016 to Jan 2017, eleven cases of HCC (average age of 51.8-year), 4 at stage B and 7 at stage C, according to Barcelona Clinic Liver Cancer staging, were treated with nivolumab. There were 4 patients with lung metastasis, 1 with portal vein tumor thrombus, 1 with abdominal metastasis and 1 with bone metastasis. The protocol was nivolumab, 3 mg/kg, on day 1, q3w...
November 14, 2017: Oncotarget
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
#7
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...
December 8, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29226090/inhibition-of-il-18-mediated-myeloid-derived-suppressor-cell-accumulation-enhances-anti-pd1-efficacy-against-osteosarcoma-cancer
#8
Ying Guan, Rui Zhang, Zhibin Peng, Daming Dong, Guojun Wei, Yansong Wang
Myeloid derived suppressor cells (MDSC) are very important in tumor immune evasion and they dramatically increased in peripheral blood of patients with osteosarcoma cancer. The association between MDSC and various cytokines has been studied in the peripheral blood. However, little is known about the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and interleukin 18 (IL-18) level in osteosarcoma tumor model and its effect on the immunotherapy. MDSC were isolated from the blood and parenchyma and analyzed in the osteosarcoma tumor model...
November 2017: Journal of Bone Oncology
https://www.readbyqxmd.com/read/29225343/advances-in-the-understanding-and-treatment-of-sepsis-induced-immunosuppression
#9
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...
December 11, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29221649/-two-cases-of-granuloma-annulare-under-anti-pd1-therapy
#10
R Charollais, F Aubin, B Roche-Kubler, E Puzenat
BACKGROUND: Granuloma annulare as a granulomatous cutaneous reaction may be drug-induced. Immune checkpoint inhibitors including programmed death-1 (PD-1) inhibitors show remarkable antitumor activity and are approved for melanoma and other cancers. Different immune-related adverse effects have been described. We report herein a rare adverse effect of anti-PD1 therapy given for metastatic melanoma : granuloma annulare. PATIENTS AND METHODS: Two women receiving pembrolizumab metastatic melanoma presented with granuloma annulare...
December 5, 2017: Annales de Dermatologie et de Vénéréologie
https://www.readbyqxmd.com/read/29217299/high-pd-l1-cd86-mfi-ratio-and-il-10-secretion-characterize-human-regulatory-dendritic-cells-generated-for-clinical-testing-in-organ-transplantation
#11
Alan F Zahorchak, Camila Macedo, David E Hamm, Lisa H Butterfield, Diana M Metes, Angus W Thomson
Human regulatory dendritic cells (DCreg) were generated from CD14 immunobead-purified or elutriated monocytes in the presence of vitamin D3 and IL-10. They exhibited similar, low levels of costimulatory CD80 and CD86, but comparatively high levels of co-inhibitory programed death ligand-1 (PD-L1) and IL-10 production compared to control immature DC (iDC). Following Toll-like receptor 4 ligation, unlike control iDC, DCreg resisted phenotypic and functional maturation and further upregulated PD-L1:CD86 expression...
September 14, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29214427/characterization-of-pd-l1-expression-in-chinese-non-small-cell-lung-cancer-patients-with-pten-expression-as-a-means-for-tissue-quality-screening
#12
Xu-Chao Zhang, Xu Cao, Chun Sun, Zhi Xie, Jian-Jun Guo, Jin-Ji Yang, Xue-Ning Yang, Hang-Jun Dai, Su-Chun Li, Xin-Ran Xu, Yun-Xia Zuo, Meng Chen, Hartmut Koeppen, Jing He, Astrid Kiermaier, David Shames, Gang Cheng, Yi-Long Wu
The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay...
December 6, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29208646/a-serum-protein-signature-associated-with-outcome-after-anti-pd1-therapy-in-metastatic-melanoma
#13
Mario Sznol, Ryan J Sullivan, Shauna Blackmon, Genevieve Boland, Harriet M Kluger, Ruth Halaban, Antonella Bacchiocchi, Paolo A Ascierto, Marilena Capone, Carlos Oliveira, Krista Meyer, Julia Grigorieva, Senait G Asmellash, Joanna Roder, Heinrich Roder, Jeffrey S Weber
A mass spectrometry analysis was performed using serum from patients receiving checkpoint inhibitors to define baseline protein signatures associated with outcome in metastatic melanoma. Pre-treatment serum was obtained from a development set of 119 melanoma patients on a trial of nivolumab with or without a multi-peptide vaccine and from patients receiving pembrolizumab, nivolumab, ipilimumab, or both nivolumab and ipilimumab. Spectra were obtained using matrix assisted laser desorption/ionization time of flight mass spectrometry...
December 5, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29206680/immune-therapies-in-acute-myeloid-leukemia-a-focus-on-monoclonal-antibodies-and-immune-checkpoint-inhibitors
#14
Rita Assi, Hagop Kantarjian, Farhad Ravandi, Naval Daver
PURPOSE OF REVIEW: This review discusses the rationale, efficacy, and toxicity of a variety of immune approaches being evaluated in the therapy of acute myeloid leukemia (AML) including naked and conjugated monoclonal antibodies, bispecific T-cell engager antibodies, and immune checkpoint blockade via antibodies targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed-death 1 (PD-1). RECENT FINDINGS: The stellar success of immune therapies that harness the power of T cells in solid tumors and an improved understanding of the immune system in patients with hematologic malignancies have resulted in major efforts to develop immune therapies for the treatment of patients with AML...
December 4, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29202855/soluble-cd73-as-biomarker-in-patients-with-metastatic-melanoma-patients-treated-with-nivolumab
#15
Silvana Morello, Mariaelena Capone, Claudia Sorrentino, Diana Giannarelli, Gabriele Madonna, Domenico Mallardo, Antonio M Grimaldi, Aldo Pinto, Paolo Antonio Ascierto
BACKGROUND: Nivolumab is an anti-PD1 checkpoint inhibitor active in patients with advanced melanoma and as adjuvant therapy in high-risk metastatic melanoma patients. METHODS: In this single-center retrospective analysis, we investigated the CD73 enzyme activity in patients with metastatic melanoma stage IV and its correlation with the response to nivolumab. The soluble CD73 (sCD73) enzyme activity was measured in the serum of 37 melanoma patients before receiving nivolumab and the Harrel's C index was used to find the best cut-off for this biomarker...
December 4, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29194117/non-small-cell-lung-cancer-from-hiv-infected-patients-expressed-pd-l1-with-marked-inflammatory-infiltrates
#16
Charlotte Domblides, Martine Antoine, Cécile Hamard, Nathalie Rabbe, Anita Rodenas, Thibault Vieira, Perrine Crequit, Jacques Cadranel, Armelle Lavolé, Marie Wislez
OBJECTIVE: Immunotherapy techniques targeting the programmed cell death protein 1 (PD-1) to PD ligand 1 (PD-L1) checkpoint have improved prognosis in lung cancer. PD-1/PD-L1 status, however, has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study sought to assess PD-L1 status and tumor immune-cell infiltration in non-small cell lung cancer (NSCLC) in HIV patients. METHODS: All consecutive HIV patients treated for NSCLC between 1996 and 2014 were enrolled...
November 30, 2017: AIDS
https://www.readbyqxmd.com/read/29191606/response-rates-to-single-agent-chemotherapy-after-exposure-to-immune-checkpoint-inhibitors-in-advanced-non-small-cell-lung-cancer
#17
Gustavo Schvartsman, S Andrew Peng, Giorgios Bis, J Jack Lee, Marcelo F K Benveniste, Jianjun Zhang, Emily B Roarty, Lara Lacerda, Stephen Swisher, John V Heymach, Frank V Fossella, William N William
INTRODUCTION: Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in overall response rate (ORR) to chemotherapy after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if single-agent chemotherapy (3rd-line or beyond) would yield improved ORR when given after exposure to programmed death-(ligand)1 inhibitors (anti-PD1) in metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We queried the Thoracic GEMINI database of MD Anderson Cancer Center for patients treated between 06/12 and 11/16 who received at least one single-agent chemotherapy as 3rd-line or beyond, following progression after platinum-based chemotherapy and anti-PD1...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29189265/development-of-a-diagnostic-programmed-cell-death-1-ligand-1-immunohistochemistry-assay-for-nivolumab-therapy-in-melanoma
#18
Therese Phillips, Molly M Millett, Xiaoling Zhang, Malinka Jansson, Rachel Cleveland, Pauline Simmons, Gregory Cherryholmes, Josette Carnahan, Josette William, Betsy Spaulding, Ilana R Satnick, H David Inzunza, Clive Taylor, John Cogswell, James Novotny, Emin Oroudjev, Henrik Winther
Nivolumab is a monoclonal antibody that blocks the interaction between programmed cell death 1 (PD1) and programmed cell death 1-ligand 1 (PD-L1), resulting in enhanced antitumor activity by the immune system. Nivolumab is currently approved by the US Food and Drug Administration (FDA) for melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, squamous cell carcinoma of the head and neck, and urothelial carcinoma. PD-L1 IHC 28-8 pharmDx is FDA-approved as a complementary diagnostic for immunohistochemical (IHC) detection of PD-L1 in non-squamous NSCLC and melanoma...
October 20, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/29174566/the-roles-of-pathology-in-targeted-therapy-of-women-with-gynecologic-cancers
#19
Rajmohan Murali, Rachel N Grisham, Robert A Soslow
The role of the pathologist in the multidisciplinary management of women with gynecologic cancer has evolved substantially over the past decade. Pathologists' evaluation of parameters such as pathologic stage, histologic subtype, grade and microsatellite instability, and their identification of patients at risk for Lynch syndrome have become essential components of diagnosis, prognostic assessment and determination of optimal treatment of affected women. Despite the use of multimodality treatment and combination cytotoxic chemotherapy, the prognosis of women with advanced-stage gynecologic cancer is often poor...
November 23, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29173980/-allogeneic-haematopoietic-cell-transplantation-for-diffuse-large-b-cell-lymphoma-guidelines-from-the-francophone-society-of-bone-marrow-transplantation-and-cellular-therapy-sfgm-tc
#20
Jordan Gauthier, Sylvain Chantepie, Krimo Bouabdallah, Edgar Jost, Stéphanie Nguyen, Anne-Claire Gac, Gandhi Damaj, Rémy Duléry, Mauricette Michallet, Jérémy Delage, Philippe Lewalle, Franck Morschhauser, Gilles Salles, Ibrahim Yakoub-Agha, Jérôme Cornillon
Despite great improvements in the outcome of patients with lymphoma, some may still relapse or present with primary refractory disease. In these situations, allogeneic hematopoietic cell transplantation is a potentially curative option, this is true particularly in the case of after autologous stem cell transplantation if remission can be achieved. Recently, novel agents such as anti-PD1 and BTK inhibitors have started to challenge the use of allogeneic hematopoietic cell transplantation for relapsed or refractory lymphoma...
November 22, 2017: Bulletin du Cancer
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