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PDL-1

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https://www.readbyqxmd.com/read/28522749/expansion-of-tumor-infiltrating-cd8-t-cells-expressing-pd-1-improves-the-efficacy-of-adoptive-t-cell-therapy
#1
Sarita M Fernandez-Poma, Diego Salas-Benito, Teresa Lozano, Noelia Casares, José-Ignacio Riezu-Boj, Uxua Mancheño, Edurne Elizalde, Diego Alignani, Natalia Zubeldia, Itziar Otano, Enrique Conde, Pablo Sarobe, Juan J Lasarte, Sandra Hervas-Stubbs
Recent studies have found that tumor-infiltrating lymphocytes (TIL) expressing PD-1 can recognize autologous tumor cells, suggesting that cells derived from PD-1+ TIL can be used in adoptive T cell therapy (ACT). However, no study thus far has evaluated the antitumor activity of PD-1-selected TIL in vivo. In two mouse models of solid tumors, we show that PD-1 allows identification and isolation of tumor-specific TIL without previous knowledge of their antigen specificities. Importantly, despite the high proportion of tumor-reactive T cells present in bulk CD8 TIL before expansion, only T cell products derived from sorted PD-1+, but not from PD-1- or bulk CD8 TIL, specifically recognized tumor cells...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28488345/patterns-of-pd-1-pd-l1-and-pd-l2-expression-in-pediatric-solid-tumors
#2
Navin Pinto, Julie R Park, Erin Murphy, Jennifer Yearley, Terri McClanahan, Lakshmanan Annamalai, Douglas S Hawkins, Erin R Rudzinski
BACKGROUND: Significant antitumor effects have been observed in a variety of malignancies via blockade of immune checkpoints. Interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 suppresses T-cell function and restricts immune-mediated tumor killing. We examined expression of these proteins in children with solid tumors, as expression may serve as biomarkers of response to this class of drugs. METHODS: Sections cut from formalin-fixed paraffin-embedded (FFPE) tissue blocks were processed and evaluated for PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC) as well as by mRNA expression...
May 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#3
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28403039/pneumotoxicity-associated-with-immune-checkpoint-inhibitor-therapies
#4
Vickie R Shannon
PURPOSE OF REVIEW: Immune checkpoint inhibitor therapies represent a new paradigm in cancer therapeutics, in which the targets are not the cancer cells, but the body's own immune system. Harnessing the immune system to better fight cancer has generated a unique spectrum of immune-related adverse events (IrAEs) that effect virtually every major organ system. Although lung involvement is less common than other forms of IrAEs, its consequences are potentially lethal. This review focuses on the evolving spectrum of lung toxicities associated with the two major classes of immune checkpoint inhibitor therapies, cytotoxic T-cell ligand-4, and programed cell death-1 (PDL-1)...
April 11, 2017: Current Opinion in Pulmonary Medicine
https://www.readbyqxmd.com/read/28391420/a-neuro-oncologist-s-perspective-on-management-of-brain-metastases-in-patients-with-egfr-mutant-non-small-cell-lung-cancer
#5
REVIEW
Tresa McGranahan, Seema Nagpal
Management of non-small cell lung cancer (NSCLC) with brain metastasis (BrM) has been revolutionized by identification of molecular subsets that have targetable oncogenes. Historically, survival for NSCLC with symptomatic BrM was weeks to months. Now, many patients are surviving years with limited data to guide treatment decisions. Tumors with activating mutations in epidermal growth factor receptor (EGFRact+) have a higher incidence of BrM, but a longer overall survival. The high response rate of both systemic and BrM EGFRact+ NSCLC to tyrosine kinase inhibitors (TKIs) has led to the rapid incorporation of new therapies but is outpacing evidence-based decisions for BrM in NSCLC...
April 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28357911/advances-in-urothelial-bladder-cancer-immunotherapy-dawn-of-a-new-age-of-treatment
#6
REVIEW
Fouad Aoun, Elie El Rassy, Tarek Assi, Simone Albisinni, Joseph Katan
Urothelial bladder cancer displays a high number of somatic mutations that render these tumors more responsive to immunotherapy. Several immunotherapeutic agents were examined in patients with advanced stage urothelial bladder cancer and recently atezolizumab - an (PDL-1) immune checkpoint inhibitor antibody - was approved for the treatment of patients with metastatic disease progressing after platinum combination therapy. Despite the great success, there are still some unanswered questions and ongoing trials that are in progress to define the role of combination therapy and sequencing strategies...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#7
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28318336/are-tumor-infiltrating-lymphocytes-protagonists-or-background-actors-in-patient-selection-for-cancer-immunotherapy
#8
Federica Zito Marino, Paolo Antonio Ascierto, Giulio Rossi, Stefania Staibano, Marco Montella, Daniela Russo, Roberto Alfano, Alessandro Morabito, Gerardo Botti, Renato Franco
Tumor-infiltrating lymphocytes (TILs) are frequently observed in several tumors, reflecting the dynamic process of '"cancer immunoediting"'. Prognostic and predictive values of TILs have been demonstrated in different cancers, proving their pivotal role in clinical outcome. In recent years, new therapies targeting immune checkpoint inhibitors, especially CTLA-4 and PD-1/PDL-1 pathways, have been introduced into clinical practice. In this context, TILs may even have a possible utility as a predictive biomarker for immunotherapy response...
June 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28230773/programmed-death-ligand-1-pd-l1-tumor-expression-is-associated-with-a-better-prognosis-and-diabetic-disease-in-triple-negative-breast-cancer-patients
#9
Gerardo Botti, Francesca Collina, Giosuè Scognamiglio, Federica Rao, Valentina Peluso, Rossella De Cecio, Michela Piezzo, Gabriella Landi, Michelino De Laurentiis, Monica Cantile, Maurizio Di Bonito
Triple Negative Breast Cancers (TNBC) subtype is an aggressive disease with poor clinical outcome. The only treatment available is surgery followed by chemotherapy or radiotherapy. Programmed death-ligand 1 (PD-L1) is a trans-membrane protein expressed on a wide variety of cells including immune cells, epithelial and vascular endothelial cells. Recently, PD-1/PD-L1 pathway signaling was described as an adaptive immune resistance mechanism enacted by the tumor cells to evade the immune response. Its presence on tumor cell membranes, acquired for this reason, through time, is an important prognostic value...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28194153/nasal-polyp-derived-mesenchymal-stromal-cells-exhibit-lack-of-immune-associated-molecules-and-high-levels-of-stem-progenitor-cells-markers
#10
Pedro Wey Barbosa de Oliveira, Rogério Pezato, Juan Sebastian Henao Agudelo, Claudina Angela Perez-Novo, Wim Vanden Berghe, Niels Olsen Câmara, Danilo Candido de Almeida, Luís Carlos Gregorio
Mesenchymal stromal cells (MSCs) are considered adult progenitor stem cells and have been studied in a multitude of tissues. In this context, the microenvironment of nasal polyp tissue has several inflammatory cells, but their stroma compartment remains little elucidated. Hence, we isolated MSCs from nasal polyps Polyp-MSCs (PO-MSCs) and compared their molecular features and gene expression pattern with bone marrow-derived MSCs (BM-MSCs). Initially, both PO-MSCs and BM-MSCs were isolated, cultivated, and submitted to morphologic, differentiation, phenotypic, immunosuppressive, and gene expression assays...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28186730/engineered-hydrogen-bonded-glycopolymer-capsules-and-their-interactions-with-antigen-presenting-cells
#11
Kristian Kempe, Sue D Xiang, Paul Wilson, Md Arifur Rahim, Yi Ju, Michael R Whittaker, David M Haddleton, Magdalena Plebanski, Frank Caruso, Thomas P Davis
Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC)...
February 22, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28185198/validation-of-anti-mouse-pdl-1-goat-polyclonal-antibody-staining-with-mouse-pdl-1-in-situ-hybridization-on-adjacent-sections-of-cell-pellets-and-mouse-tumors
#12
Jacob Ricca, Mesruh Turkekul, Afsar Barlas, Dmitry Yarilin, Sho Fujisawa, Ning Fan, Matthew Brendel, Dmitriy Zamarin, Jedd D Wolchok, Katia Manova-Todorova
Finding a valid antibody to detect mouse programmed death ligand 1 (PDL-1) by immunohistochemistry or immunofluorescence staining has been notoriously difficult. Successful validation of an antibody requires the use of multiple detection methods with the ability to compare appropriate positive and negative controls. Here, we describe in detail the protocols used to validate a mouse-specific PDL-1 antibody used in immunohistochemistry staining with an mRNA in situ hybridization on adjacent sections of mouse B16 tumor...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27911476/nd-yag-and-pulsed-dye-laser-therapy-in-infantile-haemangiomas-a-retrospective-analysis-of-271-treated-haemangiomas-in-149-children
#13
F Hartmann, A Lockmann, L-L Grönemeyer, H A Haenssle, M Zutt, H von Fintel, I Kühnle, M P Schön, K-M Thoms
BACKGROUND: Infantile haemangiomas (IH) are common benign tumours in infancy. Most IH resolve spontaneously, but some require treatment due to ulceration, functional impairment or cosmetic disfiguration. While systemic propranolol is effective in many cases, laser therapy may be a safe topical alternative. OBJECTIVE: To assess the efficacy of combined Nd:YAG/pulsed dye laser (PDL) or PDL alone for therapy of IH. PATIENTS AND METHODS: A total of 271 IH in 149 infants were treated with combined Nd:YAG/PDL or PDL alone...
December 2, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/27816392/assessing-pdl-1-and-pd-1-in-non-small-cell-lung-cancer-a-novel-immunoscore-approach
#14
Erna-Elise Paulsen, Thomas K Kilvaer, Mehrdad Rakaee Khanehkenari, Samer Al-Saad, Sigurd M Hald, Sigve Andersen, Elin Richardsen, Nora Ness, Lill-Tove Busund, Roy M Bremnes, Tom Donnem
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC...
March 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27806346/cross-talk-between-microbiota-and-immune-fitness-to-steer-and-control-response-to-anti-pd-1-pdl-1-treatment
#15
REVIEW
Andrea Botticelli, Ilaria Zizzari, Federica Mazzuca, Paolo Antonio Ascierto, Lorenza Putignani, Luca Marchetti, Chiara Napoletano, Marianna Nuti, Paolo Marchetti
Immune Checkpoint Inhibitors (ICIs) are improving the survival of cancer patients, however only the 20-30% of treated patients present clinical benefits. Toxicity represents the major cause of reduced dosage, delayed drug administration and therapy discontinuation. Hence in the context of multiple treatment possibilities, the identification of predictive markers of response and toxicity is a challenging approach for drug selection in order to obtain the best clinical benefit while minimizing the side effects...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27803174/the-third-signal-cytokine-il-12-rather-than-immune-checkpoint-inhibitors-contribute-to-the-functional-restoration-of-hepatitis-d-virus-specific-t-cells
#16
Thomas Schirdewahn, Jan Grabowski, Solomon Owusu Sekyere, Birgit Bremer, Anika Wranke, Sebastian Lunemann, Verena Schlaphoff, Janina Kirschner, Svenja Hardtke, Michael Peter Manns, Markus Cornberg, Heiner Wedemeyer, Pothakamuri Venkata Suneetha
BACKGROUND:  Hepatitis D virus (HDV) infection affects 15-20 million individuals world-wide and causes severely progressive hepatitis. It is unknown to what extent cellular immune responses contribute to liver disease and control of viral replication in HDV infection. METHODS:  Immune cell frequencies and phenotypes were determined in 49 HDV-infected patients, 25 HBV-monoinfected individuals and 18 healthy controls. T-cell proliferative and cytokine-producing capacities were analysed by stimulation with overlapping peptides spanning the large HDV antigen...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27721403/cxcl2-mif-cxcr2-signaling-promotes-the-recruitment-of-myeloid-derived-suppressor-cells-and-is-correlated-with-prognosis-in-bladder-cancer
#17
H Zhang, Y-L Ye, M-X Li, S-B Ye, W-R Huang, T-T Cai, J He, J-Y Peng, T-H Duan, J Cui, X-S Zhang, F-J Zhou, R-F Wang, J Li
The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33(+) MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0...
April 2017: Oncogene
https://www.readbyqxmd.com/read/27707883/protein-kinase-ck2-controls-t-cell-polarization-through-dendritic-cell-activation-in-response-to-contact-sensitizers
#18
Marie de Bourayne, Yann Gallais, Zeina El Ali, Philippe Rousseau, Marie-Hélène Damiens, Claude Cochet, Odile Filhol, Sylvie Chollet-Martin, Marc Pallardy, Saadia Kerdine-Römer
Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO4 and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 effector T cells...
October 5, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27695530/nivolumab-in-the-treatment-of-advanced-renal-cell-carcinoma-clinical-trial-evidence-and-experience
#19
REVIEW
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27522179/hedgehog-signaling-regulates-pdl-1-expression-in-cancer-cells-to-induce-anti-tumor-activity-by-activated-lymphocytes
#20
Hideya Onishi, Akiko Fujimura, Yasuhiro Oyama, Akio Yamasaki, Akira Imaizumi, Makoto Kawamoto, Mitsuo Katano, Masayo Umebayashi, Takashi Morisaki
We investigated whether hypoxia-induced activation of Hh signaling contributes to PDL-1 expression in cancer and whether it affects the anti-tumor function of activated lymphocytes. Hypoxia augmented PDL-1 expression and inhibition of Hh signaling reduced PDL-1 expression under hypoxia. When activated lymphocytes were cocultured with cancers treated with a Hh inhibitor, activated lymphocyte cell numbers increased under hypoxia. In contrast, this increase was abrogated when cancer cells were treated with a PDL-1 neutralizing antibody...
August 8, 2016: Cellular Immunology
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