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pd1 AND lung cancer

Marion Ferreira, Eric Pichon, Delphine Carmier, Emilie Bouquet, Cécile Pageot, Theodora Bejan-Angoulvant, Marion Campana, Emmanuelle Vermes, Sylvain Marchand-Adam
Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood...
July 13, 2018: Targeted Oncology
Sebastian Kobold, Angela Krackhardt, Hans Schlösser, Dominik Wolf
Pioneering work has unraveled the role of the immune system in the development and control of cancer. This knowledge has set the basis for the successful implementation of immunotherapy into the standard of care for a large number of cancer types. Based on response rates and prolongation of overall survival, immunotherapeutic approaches have been approved in a growing number of tumor diseases. Activation or therapeutic utilization of T cells represent the basis of these concepts. Checkpoint inhibitory antibodies inhibiting CTLA-4, PD1 and PD-L1 receptors and ligands induce long-term clinical tumor control in a significant number of cancer patients including metastatic melanoma and non-small cell lung cancer...
July 2018: Deutsche Medizinische Wochenschrift
Jesus Miranda Poma, Lorena Ostios Garcia, Julia Villamayor Sanchez, Gabriele D'errico
Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs)...
July 5, 2018: Allergologia et Immunopathologia
Gianpiero Fasola, Elisa De Carlo, Francesco Grossi
The checkpoint inhibitors opened a new era in the treatment of advanced non-small-cell lung cancer (NSCLC) initially by replacing second-line standard chemotherapy with docetaxel and subsequently by replacing platinum-based chemotherapy in the first line, albeit in patients selected for a high expression of PD-L1. The decision algorithm has therefore been radically modified for patients who do not have activating mutations. However, we are only at the beginning of a new era from which we expect in the near future the use of immunotherapy in most patients as a first line treatment in substitution or in combination with chemotherapy...
June 2018: Recenti Progressi in Medicina
Jin-Hua Chen, Jia-Lian Yang, Che-Yi Chou, Jiun-Yi Wang, Chin-Chuan Hung
In this study, we conducted an indirect comparison analysis to compare the efficacy and safety of immune checkpoint inhibitors with those of antiangiogenic therapy-two effective treatment methods for advanced non-small-cell lung cancer (NSCLC). Eligible randomised control trials of immune checkpoint inhibitors, antiangiogenic therapy, and doublet platinum-based therapy published up to July 2017 were comprehensively analysed. Through the indirect comparison analysis of 37 trials involving 16810 patients, treatments were compared for overall survival (OS) and grade 3-5 adverse events...
June 26, 2018: Scientific Reports
Ana M Ramos-Levi, Jacobo Rogado, Jose Miguel Sanchez-Torres, Ramón Colomer, Mónica Marazuela
BACKGROUND: Nivolumab is an anti-cancer monoclonal antibody that inhibits PD1 and modulates T-cell response. It has been shown to significantly improve survival in several types of cancer, but clinical trials have also reported an increased risk of developing immune-related adverse events (IRAEs). Endocrine IRAEs may be particularly relevant. OBJECTIVE: To comprehensively evaluate the clinical presentation of endocrine IRAEs in patients with lung cancer treated with nivolumab...
June 14, 2018: Endocrinología, Diabetes y Nutrición
Yue Wang, Xiaokai Zhang, Liangliang Yang, Jinru Xue, Guangrui Hu
Myeloid derived suppressor cells (MDSC) play a pivotal role in tumor immune evasion and MDSC levels increased in patients with cancer. Studies confirmed the associations between MDSC and various cytokines in the peripheral blood. However, little is known about the association between parenchymal MDSC subsets and cytokines, or the mechanism drawing MDSC into tumor parenchyma. This study was to analyze the correlation between MDSC subsets and CCL2 level in lung cancer model. G-MDSC and M-MDSC from the blood and parenchyma were analyzed by flow cytometry and western blot in the lung tumor model...
June 2018: Journal of Bone Oncology
Elizabeth Ahern, Heidi Harjunpää, Jake S O'Donnell, Stacey Allen, William C Dougall, Michele W L Teng, Mark J Smyth
Receptor activator of NF-κB ligand (RANKL) and its receptor RANK, are members of the tumor necrosis factor and receptor superfamilies, respectively. Antibodies targeting RANKL have recently been evaluated in combination with anti-CTLA4 in case reports of human melanoma and mouse models of cancer. However, the efficacy of anti-RANKL in combination with antibodies targeting other immune checkpoint receptors such as PD1 has not been reported. In this study, we demonstrated that blockade of RANKL improves anti-metastatic activity of antibodies targeting PD1/PD-L1 and improves subcutaneous growth suppression in mouse models of melanoma, prostate and colon cancer...
2018: Oncoimmunology
Edwin R Parra, Pamela Villalobos, Carmen Behrens, Mei Jiang, Apar Pataer, Stephen G Swisher, William N William, Jiexin Zhang, Jack Lee, Tina Cascone, John V Heymach, Marie-Andrée Forget, Cara Haymaker, Chantale Bernatchez, Neda Kalhor, Annikka Weissferdt, Cesar Moran, Jianjun Zhang, Ara Vaporciyan, Don L Gibbons, Boris Sepesi, Ignacio I Wistuba
BACKGROUND: The clinical efficacy observed with inhibitors of programed cell death 1/programed cell death ligand 1 (PD-L1/PD-1) in cancer therapy has prompted studies to characterize the immune response in several tumor types, including lung cancer. However, the immunological profile of non-small cell lung carcinoma (NSCLC) treated with neoadjuvant chemotherapy (NCT) is not yet fully characterized, and it may be therapeutically important. The aim of this retrospective study was to characterize and quantify PD-L1/PD-1 expression and tumor-associated immune cells (TAICs) in surgically resected NSCLCs from patients who received NCT or did not receive NCT (non-NCT)...
June 6, 2018: Journal for Immunotherapy of Cancer
Ronny Ben-Avi, Ronit Farhi, Alon Ben-Nun, Marina Gorodner, Eyal Greenberg, Gal Markel, Jacob Schachter, Orit Itzhaki, Michal J Besser
Adoptive cell therapy (ACT) of tumor infiltration lymphocytes (TIL) yields promising clinical results in metastatic melanoma patients, who failed standard treatments. Due to the fact that metastatic lung cancer has proven to be susceptible to immunotherapy and possesses a high mutation burden, which makes it responsive to T cell attack, we explored the feasibility of TIL ACT in non-small cell lung cancer (NSCLC) patients. Multiple TIL cultures were isolated from tumor specimens of five NSCLC patients undergoing thoracic surgery...
May 29, 2018: Cancer Immunology, Immunotherapy: CII
Pengfei Cui, Zhefeng Liu, Guoqiang Wang, Junxun Ma, Yuanyu Qian, Fan Zhang, Chun Han, Yaping Long, Ye Li, Xuan Zheng, Danyang Sun, Jing Zhang, Shangli Cai, Shunchang Jiao, Yi Hu
Immune checkpoint blockade-related pneumonitis is a rare but potentially life-threatening adverse effect, but its risk factors are not completely understood. This case-control study was conducted to identify pneumonitis risk factors in patients treated with anti-PD1 monoclonal antibodies (mAbs), including all the patients who developed pneumonitis after anti-PD-1 mAbs treatment in the Cancer Center of the Chinese People's Liberation Army from September 2015 to September 2017. Two controls per case were matched according to a propensity-score matching algorithm to account for confounding effects caused by individual baseline variables...
May 23, 2018: Cancer Medicine
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ailin Li, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Taylor R Cushman, Mauricio S Caetano, Xiaohong Wang, David R Valdecanas, Sharareh Niknam, Ahmed I Younes, Guang Li, Wendy A Woodward, Maria Angelica Cortez, James W Welsh
Indoleamine 2,3-dioxygenase 1 (IDO1), involved in the catabolism of tryptophan (Trp) to kynurenine (Kyn) is an important regulator of tumor-mediated immunosuppression implicated in resistance to anti-PD1 immunotherapy. We investigated the role of IDO1 in an anti-PD1-resistant lung cancer model (344SQ_R) compared to the parental 344SQ tumors (344SQ_P). IDO1 was overexpressed in tumor-infiltrating leukocytes, and plasma Kyn levels were increased, in 344SQ_R vs. 344SQ_P. The IDO1 inhibitor INCB023843 retarded tumor growth and reduced lung metastases in 344SQ_R...
May 8, 2018: Cancer Letters
Sharyn I Katz, Mark Hammer, Stephen J Bagley, Charu Aggarwal, Joshua M Bauml, Jeffrey C Thompson, Arun C Nachiappan, Charles B Simone, Corey J Langer
INTRODUCTION: Anti-programmed cell death protein 1 (PD-1) therapy can lead to unconventional tumor responses, including radiologic pseudoprogression. Here we have determined the real-world incidence of radiologic pseudoprogression in advanced NSCLC and compared radiologic response criteria for assessment of disease response. METHODS: The electronic medical records of all patients with NSCLC who were receiving anti-PD-1 therapy at our institution over a 3-year period were retrospectively reviewed, and patients with clinically suspected radiologic pseudoprogression were identified...
July 2018: Journal of Thoracic Oncology
Etienne Giroux Leprieur, Guillaume Herbretau, Coraline Dumenil, Catherine Julie, Violaine Giraud, Sylvie Labrune, Jennifer Dumoulin, Julie Tisserand, Jean-François Emile, Hélène Blons, Thierry Chinet
Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of circulating tumor DNA (ctDNA) on the efficacy of nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of nivolumab and at the first tumor evaluation with nivolumab...
2018: Oncoimmunology
Enrico Munari, Giuseppe Zamboni, Gianluigi Lunardi, Luigi Marchionni, Marcella Marconi, Marco Sommaggio, Matteo Brunelli, Guido Martignoni, George J Netto, Mohammad O Hoque, Francesca Moretta, Maria Cristina Mingari, Maria Cristina Pegoraro, Alessandro Inno, Simona Paiano, Alberto Terzi, Alberto Cavazza, Giulio Rossi, Francesca Romana Mariotti, Paola Vacca, Lorenzo Moretta, Giuseppe Bogina
INTRODUCTION: Determination of programmed death ligand 1 (PD-L1) expression defines eligibility for treatment with pembrolizumab in patients with advanced NSCLC. This study was designed to better define which value across core biopsy specimens from the same case more closely reflects the PD-L1 expression status on whole sections and how many core biopsy specimens are needed for confident classification of tumors in terms of PD-L1 expression. METHODS: We built tissue microarrays as surrogates of biopsies collecting five cores per case from 268 cases and compared PD-L1 staining results obtained by using the validated clone SP263 with the results obtained by using whole tumor sections...
April 25, 2018: Journal of Thoracic Oncology
Ahmed Mekki, Laurent Dercle, Philip Lichtenstein, Aurélien Marabelle, Jean-Marie Michot, Olivier Lambotte, Jérôme Le Pavec, Eleonora De Martin, Corinne Balleyguier, Stéphane Champiat, Samy Ammari
BACKGROUND: Programmed death receptor-1 blocking antibodies (anti-PD1) are a new standard of care in many cancer types. Patients benefit from improved survival but have the risk of immune-related adverse events (irAE). We evaluated if medical imaging procedures, used for anti-tumour response assessment, can detect irAEs. MATERIALS AND METHODS: All consecutive patients treated with anti-PD1 and with a medical imaging acquisition performed within 2 weeks with irAEs ≥2 were retrospectively included...
June 2018: European Journal of Cancer
Joseph A Pinto, Carlos S Vallejos, Luis E Raez, Luis A Mas, Rossana Ruiz, Junior S Torres-Roman, Zaida Morante, Jhajaira M Araujo, Henry L Gómez, Alfredo Aguilar, Denisse Bretel, Claudio J Flores, Christian Rolfo
Background: There are well-known differences in gender outcome in non-small cell lung cancer (NSCLC) and other cancers. In this work, we evaluated several randomised clinical trials to explore the gender influence in the outcome of patients with NSCLC treated with targeted therapy and immunotherapy. Methods: We performed a series of meta-analysis to compare the gender outcome in the routine setting for overall survival and progression-free survival (PFS) in phase III randomised clinical trials comparing EGFR inhibitors versus chemotherapy (OPTIMAL, LUX-lung 3, LUX-lung 6, EURTAC, ENSURE and WTJOG); ALK inhibitors versus chemotherapy (ASCEND 4, ASCEND 5, PROFILE 1014 and NCT009323893) and anti-PD1 checkpoint inhibitors versus chemotherapy (CheckMate 017, CheckMate 026, CheckMate 057, KEYNOTE 010 and KEYNOTE 024)...
2018: ESMO Open
Toshiyuki Ishiba, Andreas-Claudius Hoffmann, Joshua Usher, Yahya Elshimali, Todd Sturdevant, Mai Dang, Yolanda Jaimes, Rama Tyagi, Ronald Gonzales, Mary Grino, Jacek K Pinski, Afsaneh Barzi, Luis E Raez, Wilfried E Eberhardt, Dirk Theegarten, Heinz-Josef Lenz, Hiroyuki Uetake, Peter V Danenberg, Kathleen Danenberg
BACKGROUND: Precision medicine and prediction of therapeutic response requires monitoring potential biomarkers before and after treatment. Liquid biopsies provide noninvasive prognostic markers such as circulating tumor DNA and RNA. Circulating tumor RNA (ctRNA) in blood is also used to identify mutations in genes of interest, but additionally, provides information about relative expression levels of important genes. In this study, we analyzed PD-L1 expression in ctRNA isolated from various cancer types...
June 7, 2018: Biochemical and Biophysical Research Communications
Sandrine Niyongere, Andreas Saltos, Jhanelle E Gray
Immune checkpoint inhibitors enhance the activation and antitumor activity of the immune system, resulting in durable response rates in a select group of patients. Cytotoxic T lymphocyte antigen 4 (CTLA4) inhibitors target the inhibitory interaction between CTLA4 and CD80 or CD86. Programmed death 1 (PD1) inhibitors target the interaction between PD1 receptors on T-cells and PD-ligand 1 (PD-L1) and PD-ligand 2, blocking the inhibitory signaling and resulting in activation of T-cell effector function. These therapeutic drugs were originally evaluated in patients with metastatic melanoma before expansion to all tumor types, including non-small cell lung cancer (NSCLC) with promising results...
February 2018: Journal of Thoracic Disease
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