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https://www.readbyqxmd.com/read/27912061/tumor-interferon-signaling-regulates-a-multigenic-resistance-program-to-immune-checkpoint-blockade
#1
Joseph L Benci, Bihui Xu, Yu Qiu, Tony J Wu, Hannah Dada, Christina Twyman-Saint Victor, Lisa Cucolo, David S M Lee, Kristen E Pauken, Alexander C Huang, Tara C Gangadhar, Ravi K Amaravadi, Lynn M Schuchter, Michael D Feldman, Hemant Ishwaran, Robert H Vonderheide, Amit Maity, E John Wherry, Andy J Minn
Therapeutic blocking of the PD1 pathway results in significant tumor responses, but resistance is common. We demonstrate that prolonged interferon signaling orchestrates PDL1-dependent and PDL1-independent resistance to immune checkpoint blockade (ICB) and to combinations such as radiation plus anti-CTLA4. Persistent type II interferon signaling allows tumors to acquire STAT1-related epigenomic changes and augments expression of interferon-stimulated genes and ligands for multiple T cell inhibitory receptors...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27872087/tim-3-expression-on-tumor-infiltrating-pd-1-cd8-t-cells-correlates-with-poor-clinical-outcome-in-renal-cell-carcinoma
#2
Clémence Granier, Charles Dariane, Pierre Combe, Virginie Verkarre, Saik Urien, Cecile Badoual, Hélène Roussel, Marion Mandavit, Patrice Ravel, Mathilde Sibony, Lucie Biard, Camelia Radulescu, Emeline Vinatier, Nadine Benhamouda, Michael Peyromaure, Stephane Oudard, Arnaud Méjean, Marc Olivier Timsit, Alain Gey, Eric Tartour
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis...
November 21, 2016: Cancer Research
https://www.readbyqxmd.com/read/27785054/prognostic-value-of-pd-l1-and-pd-1-expression-in-pulmonary-neuroendocrine-tumors
#3
Yangwei Fan, Ke Ma, Chuying Wang, Jing Ning, Yuan Hu, Danfeng Dong, Xuyuan Dong, Qianqian Geng, Enxiao Li, Yinying Wu
PURPOSE: Programmed death 1 (PD-1) receptor and its ligand, programmed death ligand-1 (PD-L1), play critical roles in the immune invasion of various tumors. This study aimed to explore the clinical significance of PD-L1/PD-1 expression in the progression of pulmonary neuroendocrine tumors (PNETs). METHODS: The expression of PD-L1 and PD-1 in 80 patients diagnosed with PNETs were investigated. Immunohistochemical analysis was performed on 80 formalin-fixed paraffin-embedded tissue specimens from PNETs and 20 corresponding cancer-adjacent tissue specimens...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27692305/the-combined-role-of-biomarkers-and-interim-pet-scan-in-prediction-of-treatment-outcome-in-classical-hodgkin-s-lymphoma-a-retrospective-european-multicentre-cohort-study
#4
Claudio Agostinelli, Andrea Gallamini, Luisa Stracqualursi, Patrizia Agati, Claudio Tripodo, Fabio Fuligni, Maria Teresa Sista, Stefano Fanti, Alberto Biggi, Umberto Vitolo, Luigi Rigacci, Francesco Merli, Caterina Patti, Alessandra Romano, Alessandro Levis, Livio Trentin, Caterina Stelitano, Anna Borra, Pier Paolo Piccaluga, Stephen Hamilton-Dutoit, Peter Kamper, Jan Maciej Zaucha, Bogdan Małkowski, Waldemar Kulikowski, Joanna Tajer, Edyta Subocz, Justyna Rybka, Christian Steidl, Alessandro Broccoli, Lisa Argnani, Randy D Gascoyne, Francesco d'Amore, Pier Luigi Zinzani, Stefano A Pileri
BACKGROUND: Early-interim fluorodeoxyglucose (FDG)-PET scan after two ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy courses (PET-2) represents the most effective predictor of treatment outcome in classical Hodgkin's lymphoma. We aimed to assess the predictive value of PET-2 combined with tissue biomarkers in neoplastic and microenvironmental cells for this disease. METHODS: We enrolled 208 patients with classical Hodgkin's lymphoma and treated with ABVD (training set), from Jan 1, 2002, to Dec 31, 2009, and validated the results in a fully matched independent cohort of 102 patients with classical Hodgkin's lymphoma (validation set), enrolled from Jan 1, 2008, to Dec 31, 2012...
October 2016: Lancet Haematology
https://www.readbyqxmd.com/read/27676581/p2-47-also-presented-as-pd1-02-the-role%C3%A2-of%C3%A2-pd-l1-expression-as-a-predictive-biomarker-in-advanced-nsclc-an-update-of-a-network-meta-analysis-track-immunotherapy
#5
Pedro Aguiar, Gilberto Lopes, Ilka Santoro, Hakaru Tadokoro, Carmelia Barreto, Ramon De Mello
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27676477/pd1-02-also-presented-as-p2-47-the-role-of-pd-l1-expression-as-a-predictive-biomarker-in-advanced-nsclc-an-update-of-a-network-meta-analysis
#6
Pedro Aguiar, Gilberto Lopes, Ilka Santoro, Hakaru Tadokoro, Carmelia Barreto, Ramon De Mello
No abstract text is available yet for this article.
October 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27663482/immuno-pharmacodynamics-for-evaluating-mechanism-of-action-and-developing-immunotherapy-combinations
#7
REVIEW
Ralph E Parchment, Andrea Regier Voth, James H Doroshow, Jay A Berzofsky
Immunotherapy has become a major modality of cancer treatment, with multiple new classes of immunotherapeutics recently entering the clinic and obtaining market approval from regulatory agencies. While the promise of these therapies is great, so is the number of possible combinations not only with each other but also with small molecule therapeutics. Furthermore, the observation of unusual dose-response relationships suggests a critical dependency of drug effectiveness on the dosage regimen (dose and schedule)...
August 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/27603288/oxidized-lipoproteins-are-associated-with-markers-of-inflammation-and-immune-activation-in-hiv-1-infection
#8
Theodoros Kelesidis, Nicholas Jackson, Grace A McComsey, Xiaoyan Wang, David Elashoff, Michael P Dube, Todd T Brown, Otto O Yang, James H Stein, Judith S Currier
OBJECTIVE: The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized HDL and LDL (HDLox and LDLox) contribute to HIV-1-related immune dysfunction. STUDY: In the AIDS Clinical Trials Group A5260, 234 HIV-infected antiretroviral therapy (ART)-naive participants were randomized to receive tenofovir-emtricitabine and protease inhibitors or raltegravir and had HIV-1 RNA less than 50 copies/ml by week 24 and thereafter...
November 13, 2016: AIDS
https://www.readbyqxmd.com/read/27591097/investigation-of-pd-l1-biomarker-testing-methods-for-pd-1-axis-inhibition-in-non-squamous-non-small-cell-lung-cancer
#9
Brandon S Sheffield, Regan Fulton, Steve E Kalloger, Katy Milne, Georgia Geller, Martin Jones, Celine Jacquemont, Susanna Zachara, Eric Zhao, Erin Pleasance, Janessa Laskin, Steven J M Jones, Marco A Marra, Stephen Yip, Brad H Nelson, Allen M Gown, Cheryl Ho, Diana N Ionescu
Inhibitors of the programmed cell death 1 (PD-1) signaling axis have recently demonstrated efficacy and are rapidly being incorporated into the treatment of non-small cell lung cancers (NSCLCs). Despite clear benefits to certain patients, the association of these responses with a predictive biomarker remains uncertain. Several different biomarkers have been proposed, with differing results and conclusions. This study compares multiple methods of biomarker testing for treatment of NSCLCs with PD1-axis inhibitors...
October 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
https://www.readbyqxmd.com/read/27539246/emerging-monoclonal-antibodies-for-the-treatment-of-renal-cell-carcinoma-rcc
#10
Michael B Atkins, George K Philips
INTRODUCTION: Advanced renal cell carcinoma (RCC) was considered refractory to most cancer therapies until the 1980s, after which immune modulating agents and targeted agents were developed. Recently the rapid development of therapeutic monoclonal antibodies targeting immune checkpoint pathways has provided significant clinical benefit in patients with many distinct cancer types. Nivolumab, an anti-PD1 monoclonal antibody showed improvement in response rate and overall survival in patients with previously treated RCC and received US FDA approval in late 2015...
September 2016: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/27496355/validated-programmed-cell-death-ligand-1-immunohistochemistry-assays-e1l3n-and-sp142-reveal-similar-immune-cell-staining-patterns-in-melanoma-when-using-the-same-sensitive-detection-system
#11
Kelly A Schats, Emily A Van Vré, Stefanie De Schepper, Carolien Boeckx, Dorien M Schrijvers, Wim Waelput, Erik Fransen, Isabelle Vanden Bempt, Bart Neyns, Ingrid De Meester, Mark M Kockx
AIMS: Tumour cell and/or immune cell programmed cell death ligand 1 (PD-L1) expression is considered as a potential biomarker for anti-PD1 and anti-PD-L1 immunotherapy. Currently, different PD-L1 assays are used. This study aims to compare the staining patterns of two PD-L1 antibody clones in melanoma metastases and correlate them with PD-L1 mRNA expression. METHODS AND RESULTS: The immunohistochemistry assays were optimized and validated independently on a Ventana Benchmark Ultra (Ventana Medical Systems Inc...
August 6, 2016: Histopathology
https://www.readbyqxmd.com/read/27471580/immune-checkpoint-inhibitors-and-prostate-cancer-a-new-frontier
#12
REVIEW
Alessandra Modena, Chiara Ciccarese, Roberto Iacovelli, Matteo Brunelli, Rodolfo Montironi, Michelangelo Fiorentino, Giampaolo Tortora, Francesco Massari
Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC), agents that provide durable disease control and long-term survival are still needed. It is a fact that a tumor-induced immunosuppressive status (mediated by aberrant activation of inhibitory immune checkpoint pathways as a mechanism to evade host immune surveillance) plays a crucial role in the pathogenesis of cancer, including prostate cancer (PC), making CRPC patients suitable candidates for immunotherapy...
April 15, 2016: Oncology Reviews
https://www.readbyqxmd.com/read/27466509/role-of-genomic-instability-in-immunotherapy-with-checkpoint-inhibitors
#13
George Yaghmour, Manjari Pandey, Catherine Ireland, Kruti Patel, Sara Nunnery, Daniel Powell, Scott Baum, Eric Wiedower, Lee S Schwartzberg, Michael G Martin
AIM: We evaluated whether tumor genome sequencing to detect the number and type of alterations could be used as a valuable biomarker for judging the potential utility of immune checkpoint inhibitors in patients with advanced cancers. MATERIALS AND METHODS: We identified patients with solid tumors who were treated with checkpoint inibitors and had received commercially available next generation sequencing (NGS). Tumors profiled by Caris Life Sciences, Foundation Medicine and Guardant360 between 2013 and 2015...
August 2016: Anticancer Research
https://www.readbyqxmd.com/read/27463642/the-evolving-role-of-monoclonal-antibodies-in-the-treatment-of-patients-with-advanced-renal-cell-carcinoma-a-systematic-review
#14
Giuseppe Di Lorenzo, Sabino De Placido, Martina Pagliuca, Matteo Ferro, Giuseppe Lucarelli, Sabrina Rossetti, Davide Bosso, Livio Puglia, Piero Pignataro, Ilaria Ascione, Ottavio De Cobelli, Michele Caraglia, Michele Aieta, Daniela Terracciano, Gaetano Facchini, Carlo Buonerba, Guru Sonpavde
INTRODUCTION: While the majority of the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors currently used for the therapy of metastatic renal cell carcinoma (mRCC) are small molecule agents inhibiting multiple targets, monoclonal antibodies are inhibitors of specific targets, which may decrease off-target effects while preserving on-target activity. A few monoclonal antibodies have already been approved for mRCC (bevacizumab, nivolumab), while many others may play an important role in the therapeutic scenario of mRCC...
July 27, 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27409159/immunotherapy-for-oesophagogastric-cancer
#15
Michael Davidson, Ian Chau
INTRODUCTION: Gastric and oesophageal cancers are a pressing global health problem with high mortality rates and poor outcomes for advanced disease. The mainstay of treatment in the palliative setting has traditionally been chemotherapy, which accrues only modest survival benefits. As with other cancer types, there is increasing interest in the use of immunotherapy approaches to improve outcomes. AREAS COVERED: This paper reviews the aetiological and genetic characteristics of oesophagogastric (OG) cancers relevant to the application of immunotherapy and outlines the historical, present-day and potential future applications of immunotherapy in their management...
October 2016: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/27349977/emerging-biomarkers-as-predictors-to-anti-pd1-pd-l1-therapies-in-advanced-melanoma
#16
Kimberly Loo, Adil Daud
Recent advances in the field of cancer immunotherapy have resulted in a surge of new therapies for patients spanning multiple cancer indications. In melanoma alone, several immunotherapies have emerged as promising agents to tackle the aggressive, often refractory disease in the advanced/metastatic setting. The Programmed Cell Death pathway, from which anti-PD-1 and anti-PD-L1 therapies were developed, has shown immense promise. Given the marked success of the PD-1/PD-L1 immunotherapies, several targets have emerged as promising biomarkers, including PD-L1 tumor expression, tumor-infiltrating T-cell markers, dendritic cell markers, TCR sequencing, neoantigens and peripheral blood markers...
June 2016: Immunotherapy
https://www.readbyqxmd.com/read/27237031/clinicopathological-and-prognostic-significance-of-programmed-cell-death-ligand-1-expression-in-lung-adenocarcinoma-and-its-relationship-with-p53-status
#17
Yoon Jin Cha, Hye Ryun Kim, Chang Young Lee, Byoung Chul Cho, Hyo Sup Shim
INTRODUCTION: PD-L1 expression is a predictive biomarker for response to anti-programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors and can be evaluated by immunohistochemistry. Results of the clinicopathologic characteristics of PD-L1-positive lung adenocarcinoma have been inconsistent in previous studies, and there are no reports on the relationship between PD-L1 expression and p53 status in lung adenocarcinoma. METHODS: We examined PD-L1 and p53 expression in a total of 323 surgically resected lung adenocarcinoma cases using anti-PD-L1 (clone SP142) and anti-p53 (clone DO-7) antibodies, and analyzed the clinicopathologic characteristics of PD-L1-positive cases and their relationship with p53 status...
July 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27122549/biomarkers-associated-with-checkpoint-inhibitors
#18
REVIEW
G Manson, J Norwood, A Marabelle, H Kohrt, R Houot
Checkpoint inhibitors (CPI), namely anti-CTLA4 and anti-PD1/PD-L1 antibodies, demonstrated efficacy across multiple types of cancer. However, only subgroups of patients respond to these therapies. Additionally, CPI can induce severe immune-related adverse events (irAE). Biomarkers that predict efficacy and toxicity may help define the patients who may benefit the most from these costly and potentially toxic therapies. In this study, we review the main biomarkers that have been associated with the efficacy (pharmacodynamics and clinical benefit) and the toxicity (irAE) of CPIs in patients...
July 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27111909/preclinical-rationale-and-clinical-considerations-for-radiotherapy-plus-immunotherapy-going-beyond-local-control
#19
Jonathan E Schoenhals, Steven N Seyedin, Chad Tang, Maria A Cortez, Sharareh Niknam, Efrosini Tsouko, Joe Y Chang, Stephen M Hahn, James W Welsh
The use of radiation for cancer therapy has expanded and sparked interest in possible synergistic effects by combining it with current immunotherapies. In this review, we present a case of a patient who responded to programmed cell death 1 (PD1) blockade and radiation therapy and discuss possible mechanisms. We provide background on the blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and PD1 checkpoints and highlight future immune-based therapies that may synergize with radiation, including cytosine-phosphate-guanine vaccines, OX40 agonists, CD40 agonists, regulatory T-cell depletion, and metabolic "rewiring" of cancer cells...
March 2016: Cancer Journal
https://www.readbyqxmd.com/read/27079802/mechanism-driven-biomarkers-to-guide-immune-checkpoint-blockade-in-cancer-therapy
#20
Suzanne L Topalian, Janis M Taube, Robert A Anders, Drew M Pardoll
With recent approvals for multiple therapeutic antibodies that block cytotoxic T lymphocyte associated antigen 4 (CTLA4) and programmed cell death protein 1 (PD1) in melanoma, non-small-cell lung cancer and kidney cancer, and additional immune checkpoints being targeted clinically, many questions still remain regarding the optimal use of drugs that block these checkpoint pathways. Defining biomarkers that predict therapeutic effects and adverse events is a crucial mandate, highlighted by recent approvals for two PDL1 diagnostic tests...
May 2016: Nature Reviews. Cancer
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