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https://www.readbyqxmd.com/read/28217128/tumor-associated-lymphatic-vessels-upregulate-pdl1-to-inhibit-t-cell-activation
#1
Lothar C Dieterich, Kristian Ikenberg, Timur Cetintas, Kübra Kapaklikaya, Cornelia Hutmacher, Michael Detmar
Tumor-associated lymphatic vessels (LVs) play multiple roles during tumor progression, including promotion of metastasis and regulation of antitumor immune responses by delivering antigen from the tumor bed to draining lymph nodes (LNs). Under steady-state conditions, LN resident lymphatic endothelial cells (LECs) have been found to maintain peripheral tolerance by directly inhibiting autoreactive T-cells. Similarly, tumor-associated lymphatic endothelium has been suggested to reduce antitumor T-cell responses, but the mechanisms that mediate this effect have not been clarified...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28214182/opportunistic-autoimmunity-secondary-to-cancer-immunotherapy-oasi-an-emerging-challenge
#2
M Kostine, L Chiche, E Lazaro, P Halfon, C Charpin, D Arniaud, F Retornaz, P Blanco, N Jourde-Chiche, C Richez, C Stavris
With "checkpoint inhibitors" targeting PD1/PD-1-ligands or CTLA-4/CD28 pathways, immunotherapy has profoundly modified therapeutic strategies in oncology. First approved in refractory metastatic neoplasms (melanoma and lung adenocarcinoma), it is now being tested broadly in other cancers and/or as adjuvant treatment. For a significant proportion of patients, immunotherapy is responsible for "immunological" events, identified as Immune-Related Adverse Events (irAEs). Owing to the increasing number of prescriptions, identification and management of specific immunological side effects is crucial and requires close collaboration between oncologists and internists and/or other organ specialists...
February 14, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28209473/analysis-of-peripheral-t-cell-lymphoma-diagnostic-workup-in-the-united-states
#3
Eric D Hsi, Steven M Horwitz, Kenneth R Carson, Lauren C Pinter-Brown, Steven T Rosen, Barbara Pro, Massimo Federico, Christian Gisselbrecht, Marc Schwartz, Lisa A Bellm, Mark Acosta, Angela M Collie, Aaron M Gruver, Bartosz J Grzywacz, Samir Turakhia, Andrei R Shustov, Ranjana H Advani, Tatyana Feldman, Mary Jo Lechowicz, Sonali M Smith, Frederick Lansigan, Anil Tulpule, Michael D Craig, John P Greer, Brad S Kahl, Joseph W Leach, Neil Morganstein, Carla Casulo, Steven I Park, Francine M Foss
BACKGROUND: With increased understanding of the unique entities, subtype-specific approaches for peripheral T-cell lymphoma (PTCL) are emerging, and more precise diagnoses are becoming increasingly important. PATIENTS AND METHODS: We analyzed the approach to the histopathologic diagnosis of PTCL using data from the comprehensive oncology measures of peripheral T-cell lymphoma (COMPLETE) study. The COMPLETE trial is a large prospective cohort study of patients with newly diagnosed PTCL in the United States...
January 10, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28199983/a-versatile-system-for-rapid-multiplex-genome-edited-car-t-cell-generation
#4
Jiangtao Ren, Xuhua Zhang, Xiaojun Liu, Chongyun Fang, Shuguang Jiang, Carl H June, Yangbing Zhao
The therapeutic potential of CRISPR system has already been demonstrated in many instances and begun to overlap with the rapidly expanding field of cancer immunotherapy, especially on the production of genetically modified T cell receptor or chimeric antigen receptor (CAR) T cells. Efficient genomic disruption of multiple gene loci to generate universal donor cells, as well as potent effector T cells resistant to multiple inhibitory pathways such as PD-1 and CTLA4 is an attractive strategy for cell therapy...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#5
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#6
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28194020/cd103-lung-dendritic-cells-ldcs-induce-stronger-th1-th17-immunity-to-a-bacterial-lung-infection-than-cd11b-hi-ldcs
#7
Sudhanshu Shekhar, Ying Peng, Shuhe Wang, Xi Yang
Recent studies suggest differential roles for CD103+ and CD11b(hi) lung dendritic cells (LDCs) in host defense against viral and bacterial infections. In this study, we examined the contribution of these LDC subsets in protective immunity to chlamydial lung infection using a Chlamydia muridarum mouse infection model. We found that CD103+ LDCs showed higher expression of costimulatory molecules (CD40, CD80 and CD86) and increased production of cytokines (IL-12p70, IL-10, IL-23 and IL-6) compared with CD11b(hi) LDCs, but the expression of programmed death-ligand 1 (PD-L1) was similar between the two subsets...
February 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28188133/pd1-blockade-with-pembrolizumab-is-highly-effective-in-relapsed-or-refractory-nk-t-cell-lymphoma-failing-l-asparaginase
#8
Yok-Lam Kwong, Thomas S Y Chan, Daryl Tan, Seok Jin Kim, Li-Mei Poon, Benjamin Mow, Pek-Lan Khong, Florence Loong, Rex Au-Yeung, Jabed Iqbal, Colin Phipps, Eric Tse
Natural killer (NK)/T-cell lymphomas failing L-asparaginse-regimens have no known salvage and are almost invariably fatal. Seven male NK/T-cell lymphoma patients (age: 49, 31-68, years) failing 2 (1-5) regimens (including L-asparaginase-regimens, and allogeneic hematopoietic stem cell transplantation, HSCT, in 2 cases), were treated with the anti-programmed-death-1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic and molecular (circulating Epstein-Barr virus, EBV, DNA) criteria...
February 10, 2017: Blood
https://www.readbyqxmd.com/read/28186088/current-status-of-immunotherapy-for-gastrointestinal-stromal-tumor
#9
REVIEW
Y Tan, J C Trent, B A Wilky, D A Kerr, A E Rosenberg
Gastrointestinal stromal tumors (GIST) contain tumor-infiltrating immune cells and their presence provides an opportunity and rationale for developing effective forms of immunotherapy. The types of tumor-infiltrating inflammatory cells and relevant immune checkpoint inhibitors are the focus of active investigation. The most numerous tumor-infiltrating inflammatory cells are tumor-associated macrophages (TAMs) and CD3+ T cells. Studies have shown that patients with GISTs that harbor increased numbers of CD3+ T cells have better outcomes...
February 10, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28180998/the-prognostic-value-and-pathobiological-significance-of-glasgow-microenvironment-score-in-gastric-cancer
#10
Zhi-Hua Zhou, Cheng-Dong Ji, Jiang Zhu, Hua-Liang Xiao, Hai-Bin Zhao, You-Hong Cui, Xiu-Wu Bian
PURPOSE: To evaluate the prognostic value and pathobiological significance of Glasgow microenvironment score (GMS), a parameter based on tumor stroma percentage and inflammatory cell infiltration, in gastric cancer. METHODS: A total of 225 cases of gastric cancer were histologically reviewed, and GMS was evaluated for each case. The association between GMS and patients' survival was investigated. Then the relationship between GMS and mismatch repair (MMR) status, Epstein-Barr virus (EBV) infection were determined using immunohistochemistry (IHC) and in situ hybridization, and the expression of PD1/PD-L1 was examined...
February 8, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28180238/atrophic-exocrine-pancreatic-insufficiency-associated-with-anti-pd1-therapy
#11
A Hoadley, N Sandanayake, G V Long
No abstract text is available yet for this article.
November 17, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28179176/peri-srs-administration-of-immune-checkpoint-therapy-for-melanoma-metastatic-to-the-brain-investigating-efficacy-and-the-effects-of-relative-treatment-timing-on-lesion-response
#12
Mehran B Yusuf, Mark J Amsbaugh, Eric Burton, Jason Chesney, Shiao Woo
OBJECTIVE(S): To investigate the efficacy of immune checkpoint therapy (ICT) administered with stereotactic radiosurgery (SRS) and determine the effects of relative treatment timing on lesion response. METHODS: A prospective institutional database of all patients with intact brain metastases treated with SRS from 2007 to 2015 was reviewed for patients diagnosed with malignant melanoma. Lesion response was determined using a modified RECIST v1.1 criteria. Patients were grouped according to if they received ICT and the timing of ICT relative to SRS...
February 4, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28178682/comprehensive-analysis-of-pd-l1-expression-in-glioblastoma-multiforme
#13
Dieter Henrik Heiland, Gerrit Haaker, Daniel Delev, Bianca Mercas, Waseem Masalha, Sabrina Heynckes, Annette Gäbelein, Dietmar Pfeifer, Maria Stella Carro, Astrid Weyerbrock, Marco Prinz, Oliver Schnell
Glioblastoma multiforme are highly malignant brain tumours with frequent genetic and epigenetic alterations. The poor clinical outcome of these tumours necessitates the development of new treatment options. Immunotherapies for glioblastoma multiforme including PD1/PD-L1 inhibition are currently tested in ongoing clinical trials. The purpose of this study was to investigate the molecular background of PD-L1 expression in glioblastoma multiforme and to find associated pathway activation and genetic alterations...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28177321/the-crystal-structure-of-pd1-a-haemophilus-surface-fibril-domain
#14
Jack Wright, Maren Thomsen, Robert Kolodziejczyk, Joshua Ridley, Jessica Sinclair, Glenn Carrington, Birendra Singh, Kristian Riesbeck, Adrian Goldman
The Haemophilus surface fibril (Hsf) is an unusually large trimeric autotransporter adhesin (TAA) expressed by the most virulent strains of H. influenzae. Hsf is known to mediate adhesion between pathogen and host, allowing the establishment of potentially deadly diseases such as epiglottitis, meningitis and pneumonia. While recent research has suggested that this TAA might adopt a novel `hairpin-like' architecture, the characterization of Hsf has been limited to in silico modelling and electron micrographs, with no high-resolution structural data available...
February 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28162296/-efficacy-of-pd-1-pd-l1%C3%A2-immune-checkpoint-inhibitors-and-pd-l1%C3%A2-testing-in-thoracic-cancers
#15
Michaël Duruisseaux, Isabelle Rouquette, Julien Adam, Alexis Cortot, Aurélie Cazes, Laure Gibault, Diane Damotte, Sylvie Lantuejoul
Tumoral immune environment is a major component of cancer. Its composition and its organization represent a reproducible characteristic of tumors and a validated prognostic factor. In non-small cell lung cancer (NSCLC), cytotoxic T CD8+ lymphocyte density, associated with a Th1 environment and tertiary lymphoid structures impacts survival. Tumor cell-immune cell interaction is targeted by PD1/PD-L1 inhibitors. In advanced NSCLC, PD1/PD-L1 inhibitors are more effective than second-line chemotherapy. Pembrolizumab outperforms first-line chemotherapy in NSCLC strongly positive for PD-L1...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28159404/-pd1-pd-l1-immunohistochemistry-in-thoracic-oncology-where-are-we
#16
Paul Hofman, Marius Ilié, Sandra Lassalle, Elodie Long, Coraline Bence, Catherine Butori, Véronique Hofman
The assays for the assessment of the PD-L1 status by immunohistochemistry are available in clinical studies in thoracic oncology to predict response to immunotherapies targeting the PD-1/PD-L1 pathway. With the arrival of this new class of molecules in second line and very soon in first line of treatment for patients with advanced or metastatic non-small cell lung cancer, these tests will certainly be required in routine once these new drugs will be granted marketing authorization. The rapid introduction of these "companion" or "complementary" tests seems essential to select patients to benefit from these effective but also expensive and sometimes toxic therapies...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28157189/identification-of-cell-type-specific-mutations-in-nodal-t-cell-lymphomas
#17
T B Nguyen, M Sakata-Yanagimoto, Y Asabe, D Matsubara, J Kano, K Yoshida, Y Shiraishi, K Chiba, H Tanaka, S Miyano, K Izutsu, N Nakamura, K Takeuchi, H Miyoshi, K Ohshima, T Minowa, S Ogawa, M Noguchi, S Chiba
Recent genetic analysis has identified frequent mutations in ten-eleven translocation 2 (TET2), DNA methyltransferase 3A (DNMT3A), isocitrate dehydrogenase 2 (IDH2) and ras homolog family member A (RHOA) in nodal T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified. We examined the distribution of mutations in these subtypes of mature T-/natural killer cell neoplasms to determine their clonal architecture. Targeted sequencing was performed for 71 genes in tumor-derived DNA of 87 cases...
January 6, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28152786/first-line-treatment-of-metastatic-nsclc-mnsclc-patients-without-actionable-mutations-in-u-s-community-oncology-clinical-practice
#18
Ashwini Arunachalam, Thomas A Burke, Xiting Cao, Amy P Abernethy, David Paul Carbone
: 307 Background: Benchmarking high quality care requires defining optimally effective practice patterns. As first step, contemporary real-world practice must be detailed. The purpose of this study is to describe patient flow from diagnosis of mNSCLC to initiation of anti-cancer drug therapy in patients without known EGFR/ALK genomic tumor aberrations; the characteristics and first-line (1L) anti-cancer treatment of these patients, including induction and maintenance therapy. METHODS: Retrospective database cohort study using data from an oncology EHR system, representing 17% of incident cancer cases from US community setting...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28151378/checkpoint-inhibition-new-treatment-options-in-urologic-cancer
#19
Daan Joost De Maeseneer, Brant Delafontaine, Sylvie Rottey
Both urothelial (UC) and renal cell cancer (RCC) are highly immunogenic tumours. Recent advances in cellular immunity understanding have resulted in a successful new class of therapeutic agents. Interaction between the programmed cell death 1 (PD1) on regulatory T-cells (Treg) and programmed cell death 1 ligand (PDL1) on cancer cells inhibits an effective immune response and is an important mechanism for cancer cells to evade the immune system. Monoclonal anti-PD1 and anti-PDL1 antibodies inhibit this interaction and are called checkpoint inhibitors...
February 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28145884/the-significance-of-programmed-cell-death-ligand-1-expression-in-resected-lung-adenocarcinoma
#20
Shafei Wu, Xiaohua Shi, Jian Sun, Yuanyuan Liu, Yufeng Luo, Zhiyong Liang, Jinghui Wang, Xuan Zeng
BACKGROUND: Lung adenocarcinoma (AD) is a common variant of non-small cell lung cancer (NSCLC). Programmed cell death protein 1/programmed cell death ligand 1 (PD1/PD-L1) are promising immunotherapy targets and its expression may be an important biomarker of predicting clinical response. In this study, we evaluated PD-L1 expression in conjunction with clinicopathological characteristics and outcomes in resected lung adenocarcinoma. RESULTS: This study included 133 cases of lung adenocarcinoma...
January 27, 2017: Oncotarget
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