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https://www.readbyqxmd.com/read/28546779/emerging-treatment-options-for-the-management-of-hodgkin-s-lymphoma-clinical-utility-of-nivolumab
#1
REVIEW
David A Bond, Lapo Alinari
Classical Hodgkin's lymphoma (cHL) is a B-cell malignancy comprised of pathologic Reed Sternberg cells with a surrounding immune-tolerant inflammatory milieu. RS cells evade immune recognition in part through programmed death ligand 1 (PD-L1) overexpression, which is genetically programmed through copy number alterations, polysomy, and amplification of the 9p24.1 locus encoding PD-L1. By engaging with PD-1+ T-cells, PD-L1 delivers a potent immune suppressive signal promoting immunologic escape of the tumor cell...
2017: Journal of Blood Medicine
https://www.readbyqxmd.com/read/28545567/cancer-immunotherapy-by-targeting-immune-checkpoints-mechanism-of-t-cell-dysfunction-in-cancer-immunity-and-new-therapeutic-targets
#2
REVIEW
Hwei-Fang Tsai, Ping-Ning Hsu
Immune checkpoints or coinhibitory receptors, such as cytotoxic T lymphocyte antigen (CTLA)-4 and programmed death (PD)-1, play important roles in regulating T cell responses, and they were proven to be effective targets in treating cancer. In chronic viral infections and cancer, T cells are chronically exposed to persistent antigen stimulation. This is often associated with deterioration of T cell function with constitutive activation of immune checkpoints, a state called 'exhaustion', which is commonly associated with inefficient control of tumors and persistent viral infections...
May 25, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28545019/circulating-soluble-programmed-death-1-levels-may-differentiate-immune-tolerant-phase-from-other-phases-and-hepatocellular-carcinoma-from-other-clinical-diseases-in-chronic-hepatitis-b-virus-infection
#3
Na Li, Zhihua Zhou, Fang Li, Jiao Sang, Qunying Han, Yi Lv, Wenxuan Zhao, Chunyan Li, Zhengwen Liu
Programmed death-1 (PD-1) is involved in the immune dysfunction of hepatitis B virus (HBV) infection and hepatocellular carcinoma (HCC). This study analyzed the association of circulating soluble PD-1 (sPD-1) levels with the phases and clinical diseases in chronic HBV infection. Serum sPD-1 levels were determined by enzyme linked immunosorbent assay in patients with different phases and liver diseases of chronic HBV infection. The sPD-1 levels in patients with chronic HBV infection were significantly elevated compared with HBV infection resolvers or healthy controls...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28544524/increase-of-cells-expressing-pd-1-and-pd-l1-and-enhancement-of-ifn-%C3%AE-production-via-pd-1-pd-l1-blockade-in-bovine-mycoplasmosis
#4
Shinya Goto, Satoru Konnai, Tomohiro Okagawa, Asami Nishimori, Naoya Maekawa, Satoshi Gondaira, Hidetoshi Higuchi, Masateru Koiwa, Motoshi Tajima, Junko Kohara, Satoshi Ogasawara, Yukinari Kato, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
INTRODUCTION: Bovine mycoplasma, chiefly Mycoplasma bovis, is a pathogen that causes pneumonia, mastitis, arthritis, and otitis media in cattle. This pathogen exerts immunosuppressive effects, such as the inhibition of interferon production. However, the mechanisms involved in bovine mycoplasmosis have not been fully elucidated. In this study, we investigated the role of the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in immunosuppression in bovine mycoplasmosis...
May 24, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28543699/immune-and-molecular-correlates-in-melanoma-treated-with-immune-checkpoint-blockade
#5
REVIEW
Elizabeth H Byrne, David E Fisher
Immunotherapy for metastatic melanoma has a decades-long history, and the relatively recent use of checkpoint inhibitors has revolutionized treatment. Durable and sometimes complete remission of metastatic melanoma is now achievable in some patients who receive checkpoint-blocking therapy. However, it is unclear why some patients fare better than others. This review highlights several molecular indicators of response to checkpoint inhibition in metastatic melanoma, focusing on tumor programmed death ligand 1 expression, major histocompatibility complex class I expression, mutational load in the tumor, and T-cell infiltration into the tumor...
June 1, 2017: Cancer
https://www.readbyqxmd.com/read/28537531/clinical-features-of-nivolumab-induced-thyroiditis-a-case-series-study
#6
Ichiro Yamauchi, Yoriko Sakane, Yorihide Fukuda, Toshihito Fujii, Daisuke Taura, Masakazu Hirata, Keisho Hirota, Yohei Ueda, Yugo Kanai, Yui Yamashita, Eri Kondo, Masakatsu Sone, Akihiro Yasoda, Nobuya Inagaki
BACKGROUND: The programmed cell death-1 (PD-1) pathway is a novel therapeutic target in immune checkpoint therapy for cancer. It consists of the PD-1 receptor and its two ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Nivolumab is an anti-PD-1 monoclonal antibody approved for malignant melanoma, advanced non-small cell lung cancer, and advanced renal cell carcinoma in Japan. Thyrotoxicosis and hypothyroidism have both been reported in international phase 3 studies and national postmarketing surveillance of nivolumab in Japan...
May 24, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28535626/-expression-and-prognostic-significance-of-microenvironment-related-prognostic-factors-in-patients-with-classical-hodgkin-s-lymphoma
#7
T T Wang, S X Li, B Xia, H F Zhao, W Xu, H L Yang, X F Wang, Y Yu, B C Sun, Y Z Zhang
Objective: To observe the expression of three microenvironment related prognostic factors, i. e. programmed death 1 (PD-1), forkhead box protein 3(FOXP3) and colony-stimulating factor 1 receptor(CSF-1R) protein in classical Hodgkin's lymphoma (CHL) patients, and to explore the correlation between the protein expression and the prognosis of the patients. Methods: A total of 45 cases of CHL patients, who had been admitted to the Tianjin Medical University Cancer Institute and Hospital and Chinese PLA General Hospital from February 2005 to August 2010 were analyzed, including clinical features, prognostic factors, and treatment regimens...
May 16, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28535114/association-of-pd-1-5-c-t-but-not-pd-1-3-g-a-with-malignant-and-benign-brain-tumors-in-iranian-patients
#8
Fatemeh Namavar Jahromi, Morteza Samadi, Zahra Mojtahedi, Mohammad Reza Haghshenas, Mosa Taghipour, Nasrollah Erfani
Programmed death-1 (PD-1) negatively regulates the immune response. The aims of this study were to assess the association of two single nucleotide polymorphisms in the PD-1 gene, PD-1.5 (+7785 C/T-rs2227981) and PD-1.3 (+7146 G/A- rs11568821), with benign and malignant brain tumors. Patients with brain tumors (96 patients with benign and 56 with malignant brain tumors) and 150 healthy control individuals were included. PCR-RFLP was performed for genotyping. It was revealed that the genotype and allele frequencies of PD-1...
May 23, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28534248/immune-checkpoint-inhibitor-therapy-what-line-of-therapy-and-how-to-choose
#9
REVIEW
Chethan Ramamurthy, James L Godwin, Hossein Borghaei
Immunotherapy is now an established part of the treatment paradigm for advanced non-small cell lung cancer (NSCLC), but the line of therapy and the sequence of agents are still in flux. In this time when much is to be learned, the optimal therapy for most patients in both the first-line and previously treated settings is in the context of a clinical trial. For standard therapy, however, there are good data to support the practice of programmed death-ligand 1 (PD-L1) testing in the front-line advanced setting and to use pembrolizumab as first-line therapy for those with ≥50% PD-L1 expression...
June 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/28532535/-tumor-associated-fibroblasts-promote-pd-l1-expression-in-lung-cancer-cells
#10
Haiyang He, Luyu Qi, Yongsheng Xiao, Yiling Hou
BACKGROUND: Tumor-associated fibroblasts (TAF) is an important part of TME, which inhibits the function of immune cells. CD8+ T cells play a significant role in tumor immunity. T-cell membrane possesses a distinct type of molecule with a negative regulatory function. Upon interaction with its corresponding ligand [programmed death factor ligand 1 (PD-L1)], programmed death factor 1 (PD-1) is activated and thus inhibits the kinase activity of T cells. This study aims to explore the possible effects of TAF on PD-L1 expression in lung cancer cells...
May 20, 2017: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
https://www.readbyqxmd.com/read/28531337/correlation-of-immune-phenotype-with-idh-mutation-in-diffuse-glioma
#11
Anna Sophie Berghoff, Barbara Kiesel, Georg Widhalm, Dorothee Wilhelm, Orsolya Rajky, Sebastian Kurscheid, Philip Kresl, Adelheid Wöhrer, Christine Marosi, Monika E Hegi, Matthias Preusser
Background: Tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) are targets of immune checkpoint inhibitors. Methods: Forty-three World Health Organization (WHO) grade II/III gliomas (39 IDH-mutant [mut], 4 IDH-wildtype [wt]) and 14 IDH-mut glioblastomas (GBM) were analyzed for TIL (CD3+; PD1+) infiltration and PD-L1 expression. Results were compared with the data of a previously published series of 117 IDH-wt glioblastomas. PD-L1 gene expression levels were evaluated in 677 diffuse gliomas grades II-IV from The Cancer Genome Atlas (TCGA) database...
May 20, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28530525/cost-effectiveness-of-nivolumab-ipilimumab-combination-therapy-compared-with-monotherapy-for-first-line-treatment-of-metastatic-melanoma-in-the-united-states
#12
Anna Oh, Dang M Tran, Leann C McDowell, Dor Keyvani, Jay Andrew Barcelon, Oscar Merino, Leslie Wilson
BACKGROUND: The approval of new immunotherapies has dramatically changed the treatment landscape of metastatic melanoma. These survival gains come with trade-offs in side effects and costs, as well as important considerations for third-party payer systems, physicians, and patients. OBJECTIVE: To develop a Markov model to determine the cost-effectiveness of nivolumab, ipilimumab, and nivolumab-ipilimumab combination as firstline therapy in metastatic melanoma, while accounting for differential effectiveness in programmed death-ligand 1 (PD-L1) positive and negative patients...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28529902/current-state-of-immunotherapy-for-non-small-cell-lung-cancer
#13
REVIEW
Jyoti Malhotra, Salma K Jabbour, Joseph Aisner
Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%...
April 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28528510/immunogenomics-using-genomics-to-personalize-cancer-immunotherapy
#14
Rance C Siniard, Shuko Harada
While the use of genomic data has the potential to revolutionize patient care, there is still much work to be done with regard to the transformation of host-tumor interactions into favorable clinical outcomes for our patients. High-throughput technologies, such as next-generation sequencing (NGS), have rapidly advanced our understanding of oncology, and we are learning that most tumors do not simply possess consistently mutated genes that are responsible for tumorigenesis, facilitating the need for personalized cancer therapy...
May 20, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28524161/efficacy-of-anti-pd-1-therapy-in-patients-with-melanoma-brain-metastases
#15
Sagun Parakh, John J Park, Shehara Mendis, Rajat Rai, Wen Xu, Serigne Lo, Martin Drummond, Catherine Rowe, Annie Wong, Grant McArthur, Andrew Haydon, Miles C Andrews, Jonathan Cebon, Alex Guminski, Richard F Kefford, Georgina V Long, Alexander M Menzies, Oliver Klein, Matteo S Carlino
BACKGROUND: There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic. METHOD: We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS)...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28522811/pd-l1-expression-in-xp11-2-translocation-renal-cell-carcinoma-indicator-of-tumor-aggressiveness
#16
Kun Chang, Yuanyuan Qu, Bo Dai, Jian-Yuan Zhao, Hualei Gan, Guohai Shi, Yiping Zhu, Yijun Shen, Yao Zhu, Hailiang Zhang, Dingwei Ye
Programmed death ligand-1 (PD-L1), a promising antitumor target, has proven clinical value against many malignancies. However, the PD-L1 content of Xp11.2 translocation renal cell carcinoma (Xp11.2 RCC) and its correlation with clinical outcomes remain unclear. This study aimed to investigate PD-L1 expression in Xp11.2 RCC and to assess its prognostic value. Formalin-fixed paraffin-embedded specimens from 36 adult patients that were histologically confirmed (by fluorescence in situ hybridization) were subjected to immunohistochemical analysis...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522738/imaging-of-programmed-death-ligand-1-pd-l1-impact-of-protein-concentration-on-distribution-of-anti-pd-l1-spect-agent-in-an-immunocompetent-melanoma-murine-model
#17
Jessie R Nedrow, Anders Josefsson, Sunju Park, Sagar Ranka, Sanchita Roy, George Sgouros
Programmed cell Death Ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy targeting immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects (irAEs). Recently, we developed an antibody based PD-L1-targeted imaging agent to identify PD-L1 positive tumors in vivo...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28522460/soluble-pd-l1-as-a-biomarker-in-malignant-melanoma-and-checkpoint-blockade
#18
Jun Zhou, Kathleen M Mahoney, Anita Giobbie-Hurder, Fengmin Zhao, Sandra Lee, Xiaoyun Liao, Scott Rodig, Jingjing Li, Xinqi Wu, Lisa H Butterfield, Matthias Piesche, Michael P Manos, Lauren M Eastman, Glenn Dranoff, Gordon J Freeman, F Stephen Hodi
Blockade of the pathway including Programmed death-ligand 1 (PD-L1) and its receptor Programmed cell death protein 1 (PD-1) has produced clinical benefits in patients with a variety of cancers.  Elevated levels of soluble PD-L1 (sPD-L1) have been associated with worse prognosis in renal cell carcinoma and multiple myeloma.  However, the regulatory roles and function of sPD-L1 particularly in connection with immune checkpoint blockade treatment are not fully understood.  We identified four splice variants of PD-L1 in melanoma cells, and all of them are secreted...
May 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28515919/programmed-death-ligand-1-expression-is-associated-with-fibrosarcomatous-transformation-of-dermatofibrosarcoma-protuberans
#19
Kenji Tsuchihashi, Hitoshi Kusaba, Yuichi Yamada, Yuta Okumura, Hozumi Shimokawa, Masato Komoda, Keita Uchino, Tomoyasu Yoshihiro, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kyoko Inadomi, Mamoru Ito, Kosuke Sagara, Michitaka Nakano, Kenta Nio, Shuji Arita, Hiroshi Ariyama, Kenichi Kohashi, Ryuji Tominaga, Yoshinao Oda, Koichi Akashi, Eishi Baba
Dermatofibrosarcoma protuberans (DFSP) is a locally invading tumor, characterized by the presence of the collagen type I α 1 (COL1A1)-platelet-derived growth factor (PDGF) β fusion gene. We herein report the case of a 31-year-old man with a history of resection of an abdominal wall DFSP. The patient presented with chest pain and a computed tomography scan revealed a large mass in the posterior mediastinum and another mass in the right lung. The mediastinal mass was a sarcomatous lesion expressing the COL1A1-PDGFβ fusion gene, suggesting that it represented a metastasis of the DFSP following fibrosarcomatous (FS) transformation...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28515246/immunotherapies-for-lung-cancer
#20
Matthew A Gubens
In 2017, immunotherapy is the standard of care for patients with non-small cell lung cancer (NSCLC) either in the first or second line depending on programmed death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab is currently the standard of care for patients whose tumors express PD-L1 >50%. All patients with NSCLC should undergo PD-L1 testing before initiating treatment on pembrolizumab. For patients not eligible in the first line, immunotherapy is the standard of care for most in the second line...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
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