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pd1 AND lung cancer

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https://www.readbyqxmd.com/read/29127022/genetic-and-immune-profiles-of-solid-predominant-lung-adenocarcinoma-reveal-potential-immunotherapeutic-strategies
#1
Zhong-Yi Dong, Chao Zhang, Yu-Fa Li, Jian Su, Zhi Xie, Si-Yang Liu, Li-Xu Yan, Zhi-Hong Chen, Xue-Ning Yang, Jun-Tao Lin, Hai-Yan Tu, Jin-Ji Yang, Qing Zhou, Yue-Li Sun, Wen-Zhao Zhong, Yi-Long Wu
BACKGROUND: Subtype classification of lung adenocarcinoma (LUAD) divides different survivals and therapeutic vulnerabilities, while the underlying molecular mechanism is little to be known. This study sought to determine the genetic and immune profiles of histologic subtypes and identify the evidence for adjuvant immunotherapy. PATIENTS AND METHODS: We performed an integrated analysis on multidimensional data from a discovery set including cohorts of The Cancer Genome Atlas (TCGA) and the Broad set from the LUAD public database, and a validation set from the Guangdong Lung Cancer Institute (GLCI)...
November 7, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29110262/mutational-diversity-of-lung-cancer-and-associated-lymph-nodes-an-exploratory-prospective-study-of-4-resected-ciiia-n2
#2
Antoine Legras, Hélène Roussel, Giuseppe Mangiameli, Alex Arame, Bertrand Grand, Ciprian Pricopi, Alain Badia, Laure Gibault, Cécile Badoual, Elizabeth Fabre, Pierre Laurent-Puig, Hélène Blons, Françoise Le Pimpec-Barthes
Mutational heterogeneity could explain different metastatic patterns among IIIA-N2 lung cancer and influence prognosis. The identification of subclonal mutations using deep sequencing to evaluate the degree of molecular heterogeneity may improve IIIA-N2 classification. The aim of this prospective study was to assess mutational and immunohistochemical characteristics in primary tumours and involved lymph nodes (LN) in operated patients. Four patients operated for primary lung carcinoma and unisite N2 mediastinal involvement were consecutively selected...
November 6, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29096940/anti-pd1-pdl1-induced-psoriasis
#3
Dimitra Voudouri, Vasiliki Nikolaou, Konstantinos Laschos, Andriani Charpidou, Nikolaos Soupos, Ioanna Triantafyllopoulou, Ioanna Panoutsopoulou, Gerasimos Aravantinos, K Syrigos, A Stratigos
BACKGROUND: Immune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported. METHODS: We present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy...
October 18, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29082853/cancer-gene-profiling-in-non-small-cell-lung-cancers-reveals-activating-mutations-in-jak2-and-jak3-with-therapeutic-implications
#4
Shuyu D Li, Meng Ma, Hui Li, Aneta Waluszko, Tatyana Sidorenko, Eric E Schadt, David Y Zhang, Rong Chen, Fei Ye
BACKGROUND: Next-generation sequencing (NGS) of cancer gene panels are widely applied to enable personalized cancer therapy and to identify novel oncogenic mutations. METHODS: We performed targeted NGS on 932 clinical cases of non-small-cell lung cancers (NSCLCs) using the Ion AmpliSeq™ Cancer Hotspot panel v2 assay. RESULTS: Actionable mutations were identified in 65% of the cases with available targeted therapeutic options, including 26% of the patients with mutations in National Comprehensive Cancer Network (NCCN) guideline genes...
October 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/29069958/pd-l1-immunohistochemistry-for-non-small-cell-lung-carcinoma-which-strategy-should-be-adopted
#5
Paul Hofman
PD-L1 detection with immunohistochemistry (IHC) is the only predictive biomarker available to date for PD-L1/PD1 immunotherapy in thoracic oncology. While many studies have been published on this biomarker, they raise a number of questions concerning mainly, i) the type of antibody for use and its condition of utilization, ii) the threshold to be used, iii) the message and information to communicate to the thoracic oncologist and, iv) the adoption of this methodology as part of the daily practices of a pathology laboratory...
October 26, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29045514/exploratory-analysis-of-the-association-of-depth-of-response-and-survival-in-patients-with-metastatic-non-small-cell-lung-cancer-treated-with-a-targeted-therapy-or-immunotherapy
#6
C E McCoach, G M Blumenthal, L Zhang, A Myers, S Tang, R Sridhara, P Keegan, R Pazdur, R C Doebele, D Kazandjian
Background: Response Evaluation Criteria in Solid Tumors (RECIST) permits rapid evaluation of new therapeutic strategies in cancer. However, RECIST does not capture the heterogeneity of response in highly active therapies. Depth of tumor response may provide a more granular view of response. We explored the association between, depth of response (DepOR), with overall survival (OS) and progression-free survival (PFS) for patients with NSCLC being treated with an ALK inhibitor (ALKi) or an anti-PD-1 antibody (Ab)...
November 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29016555/interleukin-10-regulated-tumour-tolerance-in-non-small-cell-lung-cancer
#7
Julius Malte Vahl, Juliane Friedrich, Susanne Mittler, Sonja Trump, Lisanne Heim, Katerina Kachler, Liubov Balabko, Nicole Fuhrich, Carol-Immanuel Geppert, Denis Iulian Trufa, Nina Sopel, Ralf Rieker, Horia Sirbu, Susetta Finotto
BACKGROUND: Lung cancer is the most life-threatening cancer type worldwide. Treatment options include surgery, radio- and chemotherapy, as well as the use of immunomodulatory antibodies. Interleukin (IL)-10 is an immunosuppressive cytokine involved in tumour immune escape. METHODS: Immunohistochemistry (IHC) on human lung surgery tissue as well as human tumour cell line cultures, FACS analysis, real-time PCR and experimental lung cancer. RESULTS: Here we discovered a positive correlation between IL-10 and IL-10 receptor (IL-10R) expression in the lung with tumour diameter in patients with lung cancer (non-small cell lung cancer), the most life-threatening cancer type worldwide...
October 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28982616/the-yin-and-yang-of-leukotriene-b4-mediated-inflammation-in-cancer
#8
REVIEW
Venkatakrishna R Jala, Sobha R Bodduluri, Shuchismita R Satpathy, Zinal Chheda, Rajesh K Sharma, Bodduluri Haribabu
The high affinity leukotriene B4 receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB4/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB4/BLT1 axis enabling distinct outcomes toward tumor progression. In a mouse lung tumor model promoted by silicosis-induced inflammation, genetic deletion of BLT1 attenuated neutrophilic inflammation and tumor promotion...
October 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28948509/beyond-the-percentages-of-pd-l1-positive-tumor-cells-induced-versus-constitutive-pd-l1-expression-in-primary-and-metastatic-head-and-neck-squamous-cell-carcinoma
#9
Theresa Scognamiglio, Yao-Tseng Chen
Anti-PD1 antibody has been approved for metastatic squamous cell carcinoma of the head and neck (SCCHN) and objective response rates of approximately 20% have been reported. Defining PD-L1 expression at ≥ 1% tumor cells as positive, PD-L1-positive tumors showed a higher response rate. However, it is unclear whether 1% is the optimal cutoff, and studies on lung cancer suggested 50% cutoff as a stronger predictive biomarker. 96 primary SCCHN from oropharynx and oral cavity and 34 corresponding metastatic lesions were typed for membranous PD-L1 expression...
September 25, 2017: Head and Neck Pathology
https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#10
Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, Xiao-Feng Chen
LAG3 is a surface molecule found on a subset of immune cells. The precise function of LAG3 appears to be context-dependent. In this study, we investigated the effect of LAG3 on CD4(+)CD25(-) T cells from non-small cell lung cancer (NSCLC) patients. We found that in the peripheral blood mononuclear cells of NSCLC patients, LAG3 was significantly increased in CD4(+) T cells directly ex vivo and primarily in the CD4(+)CD25(-) fraction, which was regulated by prolonged TCR stimulation and the presence of IL-27...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28932634/pd1-positive-tumor-infiltrating-lymphocytes-are-associated-with-poor-clinical-outcome-after-pulmonary-metastasectomy-for-colorectal-cancer
#11
Dagmar Kollmann, Thomas Schweiger, Stefan Schwarz, Desislava Ignatova, Yun-Tsan Chang, Gerrit Lewik, Sebastian F Schoppmann, Wolfram Hoetzenecker, Walter Klepetko, Emmanuella Guenova, Konrad Hoetzenecker
Pulmonary metastasectomy (PM) is routinely performed in colorectal cancer (CRC) patients with oligometastatic spreading to the lungs. Patients with an aggressive tumor phenotype should be excluded from PM, since its benefit is outweighed by early tumor recurrence and impaired prognosis. Expression of PD-1 and its ligands are prognostic factors in a variety of primary tumors. However, their impact on patients' outcome in the setting of PM for CRC has not been evaluated before. 53 CRC patients with pulmonary metastases receiving PM with curative intent were included in this study...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28925793/sequential-administration-of-mva-based-vaccines-and-pd-1-pd-l1-blocking-antibodies-confers-measurable-benefits-on-tumor-growth-and-survival-preclinical-studies-with-mva-%C3%AE-gal-and-mva-muc1-tg4010-in-a-murine-tumor-model
#12
Christelle Remy-Ziller, Christine Thioudellet, Julie Hortelano, Murielle Gantzer, Virginie Nourtier, Marie-Christine Claudepierre, Benoit Sansas, Xavier Préville, Kaïdre Bendjama, Eric Quemeneur, Karola Rittner
TG4010, a Modified Vaccinia virus Ankara (MVA) expressing human mucin1 (MUC1) has demonstrated clinical benefit for patients suffering from advanced non-small cell lung cancer (NSCLC) in combination with chemotherapy. To support its development, preclinical experiments were performed with either TG4010 or β-galactosidase-encoding MVA vector (MVA-βgal) in mice presenting tumors in the lung. Tumor growth was obtained after intravenous injection of CT26 murine colon cancer cells, engineered to express either MUC1 or βgal...
September 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28892775/challenges-and-perspectives-in-the-immunotherapy-of-hodgkin-lymphoma
#13
REVIEW
Jean-Marie Michot, Julien Lazarovici, David Ghez, Alina Danu, Christophe Fermé, Amélie Bigorgne, Vincent Ribrag, Aurélien Marabelle, Sandrine Aspeslagh
Hodgkin lymphoma (HL) was one of the first few cancers to be cured first with radiotherapy alone and then with a combination of chemotherapy and radiotherapy. Around 80% of the patients with HL will be cured by first-line therapy. However, the ionising radiation not only produces cytotoxicity but also induces alterations in the microenvironment, and patients often struggle with the long-term consequences of these treatments, such as cardiovascular disorders, lung diseases and secondary malignancies. Hence, it is essential to improve treatments while avoiding delayed side-effects...
November 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28884747/adverse-prognostic-value-of-pd-l1-expression-in-primary-resected-pulmonary-squamous-cell-carcinomas-and-paired-mediastinal-lymph-node-metastases
#14
Manuel D Keller, Christina Neppl, Yasin Irmak, Sean R Hall, Ralph A Schmid, Rupert Langer, Sabina Berezowska
Immunohistochemical assessment of programmed cell death (PD)-ligand 1 (PD-L1) expression in lung cancer in the context of therapeutically targeting the PD1/PD-L1 axis is still controversially discussed. This includes the comparability of antibody clones, prognostic value, and discrepancies between primary tumors and metastases. We assessed tumoral PD-L1 expression using clones E1L3N and SP142 in 372 primary resected pulmonary squamous cell carcinomas, including 40 paired N2 lymph node metastases, in relation with clinico-pathological parameters...
September 8, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28871357/-immunotherapy-as-modern-tumor-treatment
#15
REVIEW
C Grüllich
BACKGROUND: The specific immune system is capable of preventing the development of tumor diseases and stimulation of cytotoxic T‑lymphocytes can repress existing tumors. The activation of T‑lymphocytes is influenced by a new class of antibody-based medication, the immune checkpoint inhibitors. METHODS: Review of the scientific background and the published clinical trials on the activity and approval of immune checkpoint inhibitors for various tumor diseases...
September 4, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28870260/programmed-cell-death-ligand-1-cut-point-is-associated-with-reduced-disease-specific-survival-in-resected-pancreatic-ductal-adenocarcinoma
#16
Basile Tessier-Cloutier, Steve E Kalloger, Mohammad Al-Kandari, Katy Milne, Dongxia Gao, Brad H Nelson, Daniel J Renouf, Brandon S Sheffield, David F Schaeffer
BACKGROUND: Programmed cell death 1 (PD1) inhibitors have recently shown promising anti-cancer effects in a number of solid tumor types. A predictive biomarker to this class of drugs has not been clearly identified; however, overexpression of the PD1 ligand (PD-L1) has shown particular promise in lung adenocarcinoma. In this study, we explore the staining characteristics, prevalence, and clinico-molecular correlates of PD-L1 overexpression in pancreatic ductal adenocarcinoma (PDAC). METHODS: A tissue microarray (TMA) was constructed from cases of resected PDAC...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28818609/multicenter-comparison-of-22c3-pharmdx-agilent-and-sp263-ventana-assays-to-test-pd-l1-expression-for-nsclc-patients-to-be-treated-with-immune-checkpoint-inhibitors
#17
Antonio Marchetti, Massimo Barberis, Renato Franco, Graziano De Luca, Maria Vittoria Pace, Stefania Staibano, Marco Volante, Fiamma Buttitta, Elena Guerini-Rocco, Luisella Righi, Tommaso D'antuono, Giorgio V Scagliotti, Carmine Pinto, Gaetano De Rosa, Mauro Papotti
INTRODUCTION: Among the several agents targeting the programmed cell death 1 (PD-1) pathway, pembrolizumab is currently the only one approved for the treatment of patients with NSCLC in association with a companion diagnostic assay, the anti-PD-L1 immunohistochemical (IHC) 22C3 PharmDx (Agilent Technologies, Santa Clara, CA) using the Dako Autostainer (Dako, Carpinteria, CA). However, the Dako platform is not present in each pathology department, and this technical limitation is a major problem for the diffusion of the PD-L1 IHC predictive test for pembrolizumab...
November 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#18
REVIEW
Zachary Benson, Saeed H Manjili, Mehran Habibi, Georgi Guruli, Amir A Toor, Kyle K Payne, Masoud H Manjili
Recent advances in the treatment of melanoma and non-small cell lung cancer (NSCLC) by combining conventional therapies with anti-PD1/PD-L1 immunotherapies, have renewed interests in immunotherapy of cancer. The emerging concept of conventional cancer therapies combined with immunotherapy differs from the classical concept in that it is not simply taking advantage of their additive anti-tumor effects, but it is to use certain therapeutic regimens to condition the tumor microenvironment for optimal response to immunotherapy...
December 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#19
REVIEW
Fernando C Santini, Charles M Rudin
The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology...
September 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28707167/supportive-care-for-patients-undergoing-immunotherapy
#20
Bernardo Leon Rapoport, Ronwyn van Eeden, Vincent Sibaud, Joel B Epstein, Jean Klastersky, Matti Aapro, Devan Moodley
Immune checkpoint inhibitors, a new class of cancer therapeutic agents, play an important role in the management of melanoma, NSCLC, and other malignancies. A workshop organized by three MASCC Study Groups: Oral Care, Skin Toxicities, and Neutropenia, Infection, and Myelosuppression during the MASCC Annual Meeting held in Adelaide, Australia on 23-25 June, 2016 focused on the new class of anti-cancer therapeutic agents. Topics in the workshop included the mechanism of action and clinical uses of immune anti-CTL4 and anti-PD1 antibodies, checkpoint inhibitor toxicities, including skin adverse events, gastrointestinal toxicities, oral complications, pulmonary toxicities, and endocrinological and immune-related infections...
July 13, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
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