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https://www.readbyqxmd.com/read/28935468/function-and-regulation-of-lag3-on-cd4-cd25-t-cells-in-non-small-cell-lung-cancer
#1
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...
September 18, 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
#2
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
#3
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
#4
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...
September 8, 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
#5
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
#6
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
#7
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
#8
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 non-small cell lung cancer patients in association with a companion diagnostic assay, the anti-programmed cell death ligand 1 (PD-L1) immunohistochemical (IHC) 22C3 PharmDx (Agilent) using the Dako Autostainer. 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...
August 14, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28803721/conditioning-neoadjuvant-therapies-for-improved-immunotherapy-of-cancer
#9
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...
August 10, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28714780/atezolizumab-for-the-treatment-of-non-small-cell-lung-cancer
#10
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
#11
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
https://www.readbyqxmd.com/read/28700789/hair-repigmentation-during-immunotherapy-treatment-with-an-anti-programmed-cell-death-1-and-anti-programmed-cell-death-ligand-1-agent-for-lung-cancer
#12
Noelia Rivera, Aram Boada, M Isabel Bielsa, M Teresa Fernández-Figueras, Enric Carcereny, M Teresa Moran, Carlos Ferrándiz
Importance: New targeted therapies for cancer have been released in recent years, opening new horizons in the treatment of patients with cancer. However, their related adverse events (AE) are not fully characterized. Hair repigmentation (HR) is a nondescribed effect secondary to anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1 ) therapy for treatment of lung cancer (LC), in opposition to the vitiligo reactions that develop during melanoma treatment...
July 12, 2017: JAMA Dermatology
https://www.readbyqxmd.com/read/28684311/hippo-effector-yap-directly-regulates-the-expression-of-pd-l1-transcripts-in-egfr-tki-resistant-lung-adenocarcinoma
#13
Byung Soo Lee, Dong Il Park, Da Hye Lee, Jeong Eun Lee, Min-Kyung Yeo, Yeon Hee Park, Dae Sik Lim, Wonyoung Choi, Da Hye Lee, Geon Yoo, Han-Byul Kim, Dahyun Kang, Jae Young Moon, Sung Soo Jung, Ju Ock Kim, Sang Yeon Cho, Hee Sun Park, Chaeuk Chung
Developments of EGFR-TKI and immunotherapy targeting the PD1/PD-L1 pathway are considered most important medical breakthroughs in lung cancer treatment. Nowadays, 3rd generation EGFR TKI is widely used for T790M positive 1st and 2nd EGFR-TKI resistant lung cancer patients. Immunotherapy is powerful option for lung cancer patients without drug targets and chemotherapy resistant patients. It also has changed the concept of conventional anti-cancer therapy in the point of regulating tumor microenvironment. There are many studies linking these two important pathways...
September 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28671973/pd-l1-expression-in-pleomorphic-spindle-cell-and-giant-cell-carcinoma-of-the-lung-is-related-to-ttf-1-p40-expression-and-might-indicate-a-worse-prognosis
#14
Violaine Yvorel, Arnaud Patoir, François Casteillo, Claire Tissot, Pierre Fournel, Marie-Laure Stachowicz, Georgia Karpathiou, Olivier Tiffet, Michel Péoc'h, Fabien Forest
Lung sarcomatoid carcinoma of the lung is a rare tumor with a poor prognosis. More than 90% of them are pleomorphic, spindle cell and giant cell carcinoma (PSCGCC). This rare subtype of lung cancer is thought to be more resistant to chemotherapy, and a small subset of them seems to exhibit targetable mutations. Immunotherapy against PD1/PDL-1 is a new emerging treatment, and might be of interest in PSGSCC because they frequently express PD-L1. The aim of our work is to evaluate PD1 and PDL-1 expression in a surgical series of lung PSCGCC and their relationship with morphological and immunohistochemical parameters and prognosis...
2017: PloS One
https://www.readbyqxmd.com/read/28653522/-immunotherapy-and-non-small-cell-lung-cancer-a-r-evolution
#15
T Berghmans, A P Meert
Immunotherapy renews in non-small cell lung cancer. Antibodies directed against PD1 and PD-L1, blocking the relationship between the cancer cells and the immune system, allowed in randomised trials to significantly improve cancer control with an interesting survival impact of treated patients. However, it remains to determine the most benefiting populations from this expensive and potentially toxic therapy.
2017: Revue Médicale de Bruxelles
https://www.readbyqxmd.com/read/28636292/-head-and-neck-cancer-promising-results-of-immunotherapy
#16
Aurélie Sivade, Djamila Bensaid, Yan Monnier, Keyvan Shabafrouz, Hanan Bouchaab, Valérie Cristina
Immunotherapy, especially checkpoint inhibitors such as anti-PD1 and anti-PDL1 antibodies, has changed the standard of care and the prognosis of melanoma, but also more recently of lung cancer, renal cancer and Hodgkin lymphoma. Results of preliminary studies in head and neck squamous cell carcinoma (HNSCC) as well as in less frequent tumors of the region, such as nasopharyngeal carcinoma and high grade salivary gland carcinoma, are also promising. Indeed, in a recent phase 3 study, the PD1 inhibitor nivolumab has recently demonstrated a significant improvement in overall survival for platin-resistant recurrent and/or metastatic HNSCC...
May 17, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28616701/predictive-value-of-pd-l1-based-on-mrna-level-in-the-treatment-of-stage-iv-melanoma-with-ipilimumab
#17
C Brüggemann, M C Kirchberger, S M Goldinger, B Weide, A Konrad, M Erdmann, D Schadendorf, R S Croner, L Krähenbühl, K C Kähler, C Hafner, W Leisgang, F Kiesewetter, R Dummer, G Schuler, M Stürzl, L Heinzerling
INTRODUCTION: PD-L1 is established as a predictive marker for therapy of non-small cell lung cancer with pembrolizumab. Furthermore, PD-L1 positive melanoma has shown more favorable outcomes when treated with anti-PD1 antibodies and dacarbazine compared to PD-L1 negative melanoma. However, the role of PD-L1 expression with regard to response to checkpoint inhibition with anti-CTLA-4 is not clear, yet. In addition, the lack of standardization in the immunohistochemical assessment of PD-L1 makes the comparison of results difficult...
June 14, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28613923/the-era-of-checkpoint-blockade-in-lung-cancer-taking-the-brakes-off-the-immune-system
#18
Edmund K Moon, Corey J Langer, Steven M Albelda
Despite recent advances with targeted kinase inhibitors and better-tolerated chemotherapy, the treatment of metastatic non-small-cell lung cancer remains suboptimal. One recent advance that holds great promise is immunotherapy-an approach that enhances a patient's immune system to better recognize and react to abnormal cells. The most successful immunotherapeutic strategy to date uses antibodies to block inhibitory receptors (also called "checkpoints") that are up-regulated on the T cells that infiltrate the tumor...
August 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28601918/osimertinib-reactivated-immune-related-colitis-after-treatment-with-anti-pd1-antibody-for-non-small-cell-lung-cancer
#19
Tomoyoshi Takenaka, Koji Yamazaki, Naoko Miura, Naohiko Harada, Sadanori Takeo
We reported a case of relapsing immune-related colitis (initially caused by nivolumab) following osimertinib therapy for lung adenocarcinoma. A 45-year-old female who had never smoked was diagnosed with adenocarcinoma of the lung and underwent surgical resection. Four years after surgical resection, she was diagnosed with recurrent disease and was eventually treated with nivolumab as third-line therapy. One month after the completion of nivolumab therapy, the patient reported abdominal pain and frequent diarrhea...
June 10, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/28600190/understanding-the-checkpoint-blockade-in-lung-cancer-immunotherapy
#20
REVIEW
Maria Giovanna Dal Bello, Angela Alama, Simona Coco, Irene Vanni, Francesco Grossi
Immunotherapies have changed the treatment strategy of some types of tumor including melanoma and, more recently, non-small-cell lung cancer (NSCLC). Immune checkpoints are crucial for the maintenance of self-tolerance and it is known that some tumors use checkpoint systems to evade antitumor immune response. The treatment of advanced NSCLC by immune-checkpoint blockade targeting the programmed cell death protein-1 (PD1/PDL1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) pathways has led to significant clinical benefit either as monotherapy or in combination therapy...
August 2017: Drug Discovery Today
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