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https://read.qxmd.com/read/30711957/cancer-site-and-adverse-events-induced-by-immune-checkpoint-inhibitors-a-retrospective-analysis-of-real-life-experience-at-a-single-institution
#1
Ammar Sukari, Misako Nagasaka, Roba Alhasan, Dhaval Patel, Antoinette Wozniak, Radhakrishnan Ramchandren, Ulka Vaishampayan, Amy Weise, Lawrence Flaherty, Hyejeong Jang, Seongho Kim, Shirish Gadgeel
BACKGROUND: Data on the characteristics of patients who are likely to experience adverse events, both immune-related and non-immune-related, from programmed cell death-1 (PD1) inhibitors are limited. PATIENTS AND METHODS: Data from patients who received ≥1 dose of single-agent PD1 inhibitor between August 3, 2011 and August 31, 2016 were obtained from our Institution's pharmacy database. AEs were graded using Common Terminology Criteria for Adverse Events version 4...
February 2019: Anticancer Research
https://read.qxmd.com/read/30686563/-can-nivolumab-be-used-safely-in-idiopathic-pulmonary-fibrosis
#2
B Duchemann, M Didier, M-C Pailler, P-Y Brillet, M Kambouchner, Y Uzunhan, O Freynet, K Chouahnia, L Zelek, H Nunes
Anti-PD1 immunotherapies have become an essential treatment for bronchial cancer. According to published studies, PD1 and PD-L1 inhibitors have a better toxicity profile than chemotherapy. Nevertheless, some immune related toxicities can be potentially severe, such as induced interstitial lung disease (ILD). Currently, ILD patients are excluded from clinical trials using immunotherapy in lung cancer. IPF is the most frequent and severe form of ILD. Lung cancer represents a major complication of this disease and to date few data exist on the safety of immunotherapy in this context...
January 24, 2019: Revue des Maladies Respiratoires
https://read.qxmd.com/read/30686251/efficacy-and-safety-of-addition-of-anti-pd1-to-chemotherapy-in-treatment-of-non-small-cell-lung-cancer
#3
Chu-Hui Ru, Yan-Bing Zhuang
BACKGROUND: Patients with previously treated non-small-cell lung cancer (NSCLC) have limited treatment options. A novel treatment based on programed death 1 (PD-1)/programed death ligand 1 (PD-L1) inhibitors has emerged as promising therapeutic options for advanced NSCLC. We assessed oncological outcomes of PD-L1 antibody versus docetaxel in previously treated NSCLC. OBJECTIVES: The purpose of this meta-analysis was to analysis the oncological outcomes of anti-PD1 to chemotherapy in treatment of non-small-cell lung cancer...
January 25, 2019: Combinatorial Chemistry & High Throughput Screening
https://read.qxmd.com/read/30639618/prognostic-impact-of-tumor-cell-pd-l1-expression-and-immune-cell-infiltration-in-nsclc
#4
Karolina Edlund, Katrin Madjar, Johanna S M Mattsson, Dijana Djureinovic, Cecilia Lindskog, Hans Brunnström, Hirsh Koyi, Eva Brandén, Karin Jirström, Fredrik Pontén, Jörg Rahnenführer, Patrick Micke, Jan G Hengstler
INTRODUCTION: Infiltration of T and B/plasma cells has been linked to non-small cell lung cancer (NSCLC) prognosis, but this has not been thoroughly investigated in relation to the expression of programmed cell death ligand 1 (PD-L1). Here, we determine the association of lymphocytes and PD-L1 with overall survival (OS) in two retrospective cohorts of operated NSCLC patients, who were not treated with checkpoint inhibitors targeting the PD1/PD-L1 axis. Moreover, we evaluate how PD-L1 positivity and clinicopathological factors affect the prognostic association of lymphocytes...
January 9, 2019: Journal of Thoracic Oncology
https://read.qxmd.com/read/30637710/the-role-of-immunotherapy-in-small-cell-lung-cancer
#5
REVIEW
A Calles, G Aguado, C Sandoval, R Álvarez
Despite decades of research, prognosis for SCLC patients remains poor, and treatment options limited. SCLC is an immunogenic tumor with high somatic mutation rates due to tobacco exposure resulting in potential neo-antigens, the presence of suppressed immune responses, and occurrence of paraneoplastic disorders. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients...
January 12, 2019: Clinical & Translational Oncology
https://read.qxmd.com/read/30584321/efficacy-and-safety-of-pd1-pdl1-blockades-versus-docetaxel-in-patients-with-pretreated-advanced-non-small-cell-lung-cancer-a-meta-analysis
#6
Jixiang Liu, Yulan Zhong, Shanshan Peng, Xiangxiang Zhou, Xin Gan
Background: PD1/PDL1 blockade is a promising treatment for patients with non-small-cell lung cancer (NSCLC). Here, we employed meta-analysis to evaluate the efficacy and safety of PD1/PDL1 blockades for previously treated NSCLC patients. Methods: Randomized clinical trials were retrieved by searching electronic databases. Data for HRs, 95% CIs for overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were extracted and pooled. Results: A total of five randomized controlled trials including 2,910 patients were included in this meta-analysis...
2018: OncoTargets and Therapy
https://read.qxmd.com/read/30541742/dynamics-of-tumor-and-immune-responses-during-immune-checkpoint-blockade-in-non-small-cell-lung-cancer
#7
Valsamo Anagnostou, Patrick M Forde, James R White, Noushin Niknafs, Carolyn Hruban, Jarushka Naidoo, Kristen A Marrone, I K Ashok Sivakumar, Daniel C Bruhm, Samuel Rosner, Jillian Phallen, Alessandro Leal, Vilmos Adleff, Kellie N Smith, Tricia R Cottrell, Lamia Rhymee, Doreen N Palsgrove, Christine L Hann, Benjamin Levy, Josephine Feliciano, Christos Georgiades, Franco Verde, Peter Illei, Qing Kay Li, Edward Gabrielson, Malcolm V Brock, James M Isbell, Jennifer L Sauter, Janis Taube, Robert B Scharpf, Rachel Karchin, Drew M Pardoll, Jamie E Chaft, Matthew D Hellmann, Julie R Brahmer, Victor E Velculescu
Despite the initial successes of immunotherapy, there is an urgent clinical need for molecular assays that identify patients more likely to respond. Here we report that ultrasensitive measures of circulating tumor DNA (ctDNA) and T cell expansion can be used to assess responses to immune checkpoint blockade in metastatic lung cancer patients (N=24). Patients with clinical response to therapy had a complete reduction in ctDNA levels after initiation of therapy whereas, non-responders had no significant changes or an increase in ctDNA levels...
December 12, 2018: Cancer Research
https://read.qxmd.com/read/30529597/brief-report-pembrolizumab-in-combination-with-erlotinib-or-gefitinib-as-first-line-therapy-for-advanced-non-small-cell-lung-cancer-with-sensitizing-egfr-mutation
#8
James Chih-Hsin Yang, Shirish M Gadgeel, Lecia Van Dam Sequist, Chien-Liang Wu, Vassiliki A Papadimitrakopoulou, Wu-Chou Su, Joseph Fiore, Sanatan Saraf, Harry Raftopoulos, Amita Patnaik
INTRODUCTION: Anti-EGFR agents are standard treatments for patients with EGFR-mutant advanced NSCLC. The feasibility of combining erlotinib or gefitinib with anti-PD1 immunotherapy pembrolizumab was evaluated in the phase 1/2 KEYNOTE-021 (NCT02039674) study. METHODS: Adults with previously untreated stage IIIB/IV EGFR-mutant NSCLC were treated with pembrolizumab 2 mg/kg IV every 3 weeks plus oral erlotinib 150 mg daily in cohort E or oral gefitinib 250 mg daily in cohort F, using a 3+3 design with cohort expansion...
December 4, 2018: Journal of Thoracic Oncology
https://read.qxmd.com/read/30524886/an-observational-study-of-concomitant-immunotherapies-and-denosumab-in-patients-with-advanced-melanoma-or-lung-cancer
#9
Alexander Liede, Rohini K Hernandez, Sally W Wade, Ronghai Bo, Nathan C Nussbaum, Elizabeth Ahern, William C Dougall, Mark J Smyth
After a case report of profound clinical response in a melanoma patient following treatment with an immune checkpoint inhibitor (ICI) and RANK-ligand inhibitor denosumab, we identified similar patients from electronic health records (EHR) and described patient characteristics and outcomes. This 2017 observational study used Flatiron Health's EHR database from ~255 US cancer clinics. Included were advanced melanoma or non-small-cell lung cancer (NSCLC) patients who received denosumab within 30 days of CTLA-4 (ipilimumab) or PD1 (pembrolizumab, nivolumab) inhibitors start with a minimum of 6 months of follow up...
2018: Oncoimmunology
https://read.qxmd.com/read/30470260/peripheral-blood-biomarkers-correlate-with-outcomes-in-advanced-non-small-cell-lung-cancer-patients-treated-with-anti-pd-1-antibodies
#10
Aixa E Soyano, Bhagirathbhai Dholaria, Julian A Marin-Acevedo, Nancy Diehl, David Hodge, Yan Luo, Rami Manochakian, Saranya Chumsri, Alex Adjei, Keith L Knutson, Yanyan Lou
BACKGROUND: Anti-programmed cell death 1 (PD-1) antibodies have demonstrated improved overall survival (OS) and progression-free survival (PFS) in a subset of patients with metastatic or locally advanced non-small cell lung cancer (NSCLC). To date, no blood biomarkers have been identified in NSCLC to predict clinical outcomes of treatment with anti-PD-1 antibodies. PATIENT AND METHODS: We performed an analysis of retrospectively registered data of 157 patients with advanced NSCLC treated with anti-PD-1 antibodies at Mayo Clinic in Florida and Rochester...
November 23, 2018: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/30348714/radiological-features-of-programmed-cell-death-ligand-2-positive-lung-adenocarcinoma-a-single-institution-retrospective-study
#11
Kazuki Takada, Gouji Toyokawa, Koichi Azuma, Shinkichi Takamori, Tomoko Jogo, Fumihiko Hirai, Tetsuzo Tagawa, Akihiko Kawahara, Jun Akiba, Isamu Okamoto, Yoichi Nakanishi, Yoshinao Oda, Tomoaki Hoshino, Yoshihiko Maehara
AIM: Programmed cell death-ligand 1 and 2 (PD-L1 and PD-L2) are ligands of the programmed cell death-1 (PD1) receptor. PD1/PD-L1 inhibitors have shown clinical efficacy in non-small cell lung cancer (NSCLC). However, relatively little is known about the expression of PD-L2, or its association with the clinicopathological features of NSCLC. Here, the radiological features of PD-L2-positive lung adenocarcinoma were evaluated. MATERIALS AND METHODS: PD-L1 and PD-L2 expression were evaluated by immunohistochemical staining of surgically-resected specimens from 393 patients with primary lung adenocarcinoma who underwent preoperative thin-section computed tomography (CT), 222 of whom also underwent 18 F-fluorodeoxyglucose positron-emission tomography/CT (18 F-FDG-PET/CT)...
November 2018: In Vivo
https://read.qxmd.com/read/30337201/-biomarkers-predictive-of-pd1-pd-l1-immunotherapy-in-non-small-cell-lung-cancer
#12
A Lupo, M Alifano, M Wislez, G Boulle, Y Velut, J Biton, I Cremer, F Goldwasser, K Leroy, D Damotte
Immune checkpoint inhibitors (ICI), targeting the PD1/PD-L1 axis has shown their efficacy in lung cancer but only in a restricted population of patients, thus it is mandatory to identify biomarkers predicting the clinical benefit. In this article we will describe and analyzed biomarkers already published, from protein, to RNA and at last DNA markers, discussing each markers feasibility and interest. In the future, combined analysis of several markers will probably be proposed, particularly with the increasing complexity of therapy schema with molecules association...
October 15, 2018: Revue de Pneumologie Clinique
https://read.qxmd.com/read/30323751/nivolumab-induced-impressive-response-of-refractory-pulmonary-sarcomatoid-carcinoma-with-brain-metastasis
#13
Massimiliano Salati, Cinzia Baldessari, Fiorella Calabrese, Giulio Rossi, Elisa Pettorelli, Giulia Grizzi, Massimo Dominici, Fausto Barbieri
Background: Pulmonary sarcomatoid carcinoma is a rare, poorly differentiated, and highly aggressive type of non-small cell lung cancer. High tumor mutational burden and PD-L1 overexpression make it an excellent candidate for immunotherapy. Objectives and Method: We presented the case of a patient who underwent left inferior lobectomy with concurrent right paravertebral muscular metastasectomy for an infiltrative neoplastic mass, whose final diagnosis was consistent with stage IV pulmonary sarcomatoid carcinoma...
September 2018: Case Reports in Oncology
https://read.qxmd.com/read/30305853/the-protein-expression-of-pdl1-is-highly-correlated-with-those-of-eif2-%C3%AE-and-atf4-in-lung-cancer
#14
Liang-Che Chang, Tzu-Ping Chen, Wei-Ke Kuo, Chung-Ching Hua
Introduction: The expression of programmed death 1 (PD1) and programmed death ligand 1 (PDL1) can be induced by the interferon (IFN)/signal transducer and activator of transcription (STAT) pathway. The PD1/PDL1 reverse signaling can activate the eukaryotic translation initiation factor 2 (eIF2 α )/activating transcription factor 4 (ATF4) pathway which in turn regulates the expression of IFN regulatory factor (IRF) 7 and IFN α . The eIF2 α /ATF4 pathway is responsible for the integrated stress response (ISR) of unfolded protein response (UPR) which can affect immune cell function in tumor microenvironment...
2018: Disease Markers
https://read.qxmd.com/read/30288347/combination-with-sgt-53-overcomes-tumor-resistance-to-a-checkpoint-inhibitor
#15
Sang-Soo Kim, Joe B Harford, Manish Moghe, Antonina Rait, Esther H Chang
The tumor suppressor p53 responds to genotoxic and oncogenic stresses by inducing cell cycle arrest and apoptosis. Recent studies suggest that p53 also participates in the regulation of cellular immune responses. Here, we have investigated the potential of p53 gene therapy to augment immune checkpoint inhibition by combining an anti-programmed cell death protein 1 (PD1) antibody with SGT-53, our investigational nanomedicine carrying a plasmid encoding human wild-type p53. In three syngeneic mouse tumor models examined including a breast cancer, a non-small cell lung carcinoma, and a glioblastoma, SGT-53 sensitized otherwise refractory tumors to anti-PD1 antibody...
2018: Oncoimmunology
https://read.qxmd.com/read/30268773/targeting-programmed-cell-death-1-pd-1-and-ligand-pd-l1-a-new-era-in-cancer-active-immunotherapy
#16
REVIEW
Anastasia Constantinidou, Constantinos Alifieris, Dimitrios T Trafalis
Improved understanding of the immune system and its role in cancer development and progression has led to impressive advances in the field of cancer immunotherapy over the last decade. Whilst the field is rapidly evolving and the list of drugs receiving regulatory approval for the treatment of various cancers is fast growing, the group of PD1- PDL-1 inhibitors is establishing a leading role amongst immunomodulatory agents. PD1- PDL-1 inhibitors act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade...
September 28, 2018: Pharmacology & Therapeutics
https://read.qxmd.com/read/30253973/correlation-of-pd-l1-expression-with-tumor-mutation-burden-and-gene-signatures-for-prognosis-in-early-stage-squamous-cell-lung-carcinoma
#17
Hui Yu, Zhengming Chen, Karla V Ballman, Mark A Watson, Ramaswamy Govindan, Irena Lanc, David G Beer, Raphael Bueno, Lucian R Chirieac, Michael Herman Chui, Guoan Chen, Wilbur A Franklin, David R Gandara, Carlo Genova, Kristine A Brovsky, Mary-Beth M Joshi, Daniel T Merrick, William G Richards, Christopher J Rivard, David H Harpole, Ming-Sound Tsao, Adrie van Bokhoven, Frances A Shepherd, Fred R Hirsch
OBJECTIVES: Anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) immunotherapy has demonstrated success in the treatment of advanced NSCLC. Recently, PD-1/PD-L1 blockade also has demonstrated interesting results in small trials of neoadjuvant treatment in stage IB to IIIA NSCLC. In addition, several clinical trials using anti-PD-1/PD-L1 immunotherapy as an adjuvant or neoadjuvant treatment in patients with resectable stage NSCLC are ongoing. However, few analyses of anti-PD-1/PD-L1 immunotherapy-related biomarkers in early-stage squamous cell lung carcinoma (SqCLC) have been reported...
September 22, 2018: Journal of Thoracic Oncology
https://read.qxmd.com/read/30232256/myeloid-derived-suppressor-cells-inhibit-t-cell-activation-through-nitrating-lck-in-mouse-cancers
#18
Shan Feng, Xi Cheng, Lin Zhang, Xuemin Lu, Seema Chaudhary, Ruifang Teng, Christian Frederickson, Matthew M Champion, Ren Zhao, Liang Cheng, Yiyi Gong, Haiteng Deng, Xin Lu
Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs...
October 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/30221050/the-role-of-foxp3-and-tbet-co-expressing-treg-cells-in-lung-carcinoma
#19
Katerina Kachler, Corinna Holzinger, Denis I Trufa, Horia Sirbu, Susetta Finotto
Despite the opposite roles of Tbet and Foxp3 in the immune system as well as in tumour biology, recent studies have demonstrated the presence of of CD4+ T cells, expressing both, Tbet and Foxp3. Although Tbet+ Foxp3+ T cells are currently a subject of intense research, less is known about their biological function especially in cancer. Here we found a considerable accumulation of Tbet+ Foxp3+ CD4+ T cells, mediated by the immunosuppressive cytokine TGFβ in the lungs of tumour bearing mice. This is in line with previous studies, demonstrating the important role of TGFβ for the immunopathogenesis of cancer...
2018: Oncoimmunology
https://read.qxmd.com/read/30194181/radiological-features-of-ido1-pdl1-lung-adenocarcinoma-a-retrospective-single-institution-study
#20
Kazuki Takada, Gouji Toyokawa, Tetsuzo Tagawa, Mototsugu Shimokawa, Kenichi Kohashi, Akira Haro, Atsushi Osoegawa, Yoshinao Oda, Yoshihiko Maehara
AIM: A combination of immune-checkpoint inhibitors that target the programmed cell death 1 (PD1)/programmed cell-death ligand 1 (PDL1) pathway and indoleamine 2,3-dioxygenase 1 (IDO1) is a promising treatment for non-small-cell lung cancer. Herein, we investigated clinical features of IDO1+ /PDL1+ primary lung adenocarcinoma. MATERIALS AND METHODS: IDO1 and PDL1 expression in 388 resected primary lung adenocarcinoma samples was evaluated using immunohistochemistry, and the radiological features of patients with IDO1+ /PDL1+ lung adenocarcinoma were analyzed...
September 2018: Anticancer Research
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