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Immunotherapy lung cancer

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https://www.readbyqxmd.com/read/29468660/spatiotemporal-homogeneity-and-distinctness-of-the-t-cell-receptor-%C3%AE-chain-repertoires-in-epstein-barr-virus-associated-primary-and-metastatic-nasopharyngeal-carcinomas
#1
Yih-Lin Chung, Mei-Ling Wu
Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated lymphoepithelioma. The aim of the present study was to characterize the homogeneity and distinctness of the T-cell repertoires within and between primary and metastatic NPCs. We used ultra-deep sequencing of the hypervariably rearranged antigen-binding CDR3 regions of T-cell receptor beta (TCRbeta ) to comprehensively profile the T-cell repertoires in NPC patients receiving definitive chemoradiotherapy with long-term follow-up. We observed not only various spatially heterogeneous patient-specific TCRbeta clone compositions that changed with time but also several commonly enriched TCRbeta subclones that were constantly shared between primary NPCs in the head and neck regions, locally recurrent tumors after treatment, and later-developed distant metastatic tumors in the liver, lung and bone...
February 22, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29464405/the-role-of-circulating-tumor-dna-in-renal-cell-carcinoma
#2
REVIEW
Paulo G Bergerot, Andrew W Hahn, Cristiane Decat Bergerot, Jeremy Jones, Sumanta Kumar Pal
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a novel technology that can complement tumor tissue NGS and has the potential to influence diagnosis and treatment of both localized and metastatic renal cell carcinoma (mRCC). ctDNA NGS is an attractive alternative to tumor tissue NGS because it circumvents the need for repeated, invasive tissue biopsies while providing a contemporary mutational profile of a patient's tumors. While the role of ctDNA NGS in non-small cell lung cancer and colorectal cancer is well established, studies of ctDNA NGS in mRCC are only hypothesis-generating to date...
February 20, 2018: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29464099/implications-of-kras-mutations-in-acquired-resistance-to-treatment-in-nsclc
#3
REVIEW
Marzia Del Re, Eleonora Rofi, Giuliana Restante, Stefania Crucitta, Elena Arrigoni, Stefano Fogli, Massimo Di Maio, Iacopo Petrini, Romano Danesi
Rationale: KRAS is the most common and, simultaneously, the most ambiguous oncogene implicated in human cancer. Despite KRAS mutations were identified in Non Small Cell Lung Cancers (NSCLCs) more than 20 years ago, selective and specific inhibitors aimed at directly abrogating KRAS activity are not yet available. Nevertheless, many therapeutic approaches have been developed potentially useful to treat NSCLC patients mutated for KRAS and refractory to both standard chemotherapy and targeted therapies...
January 19, 2018: Oncotarget
https://www.readbyqxmd.com/read/29456881/multimodality-treatment-of-advanced-non-small-cell-lung-cancer-where-are-we-with-the-evidence
#4
REVIEW
Christopher M Jones, Alessandro Brunelli, Matthew E Callister, Kevin N Franks
Purpose of review: The majority of patients with non-small cell lung cancer (NSCLC) present with advanced disease and overall survival rates are poor. This article outlines the current and outstanding evidence for the use of multimodality treatment in this group of patients, including in combination with an increasing number of treatment options, such as immunotherapy and genotype-targeted small molecule inhibitors. Recent findings: Optimal therapy for surgically resectable stage III disease remains debatable and currently the choice of treatment reflects each individual patient's disease characteristics and the expertise and opinion of the thoracic multi-disciplinary team...
2018: Current Surgery Reports
https://www.readbyqxmd.com/read/29455650/management-of-acquired-resistance-to-egfr-tki-targeted-therapy-in-advanced-non-small-cell-lung-cancer
#5
REVIEW
Shang-Gin Wu, Jin-Yuan Shih
Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29454155/immune-checkpoint-inhibitors-in-non-small-cell-lung-cancer-nsclc-approaches-on-special-subgroups-and-unresolved-burning-questions
#6
REVIEW
J Remon, N Vilariño, N Reguart
Immune checkpoint inhibitors (ICIs) have been incorporated in the treatment strategy of advanced non-small cell lung cancer (NSCLC). Beyond the already approved indications in first- and second-line setting of advanced NSCLC, new data has recently emerged demonstrating its efficacy in locally advanced disease as maintenance after chemo-radiotherapy and currently several trials are also exploring its efficacy in earlier stages of the disease to evaluate whether these results could be extrapolated to the adjuvant setting...
February 8, 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29454048/new-insights-into-the-molecular-characteristics-of-pulmonary-carcinoids-and-large-cell-neuroendocrine-carcinomas-and-the-impact-on-their-clinical-management
#7
REVIEW
J L Derks, N Leblay, S Lantuejoul, A M Dingemans, E J M Speel, L Fernandez-Cuesta
Carcinoids and large-cell neuroendocrine carcinomas (LCNEC) are rare neuroendocrine lung tumors. Here we provide an overview of the most updated data on the molecular characteristics of these diseases. Recent genomic studies showed that carcinoids generally contain a low mutational burden and few recurrently mutated genes. Most of the reported mutations occur in chromatin-remodeling genes (e.g. MEN1), and few affect genes of the PI3K-AKT-mTOR pathway. Aggressive disease has been related to chromothripsis, DNA-repair gene mutations, loss of OTP/CD44, and upregulation of RET gene expression...
February 14, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29453437/enhancement-of-immunomodulative-effect-of-lactic-acid-bacteria-on-plasmacytoid-dendritic-cells-with-sucrose-palmitate
#8
Masaya Kanayama, Yukiko Kato, Toshikazu Tsuji, Yuki Konoeda, Akiko Hashimoto, Osamu Kanauchi, Toshio Fujii, Daisuke Fujiwara
Plasmacytoid dendritic cells (pDCs) play a key role in the immune response against viruses. In addition, recent research has suggested that pDCs possess direct and indirect tumoricidal activities. We previously found that a lactic acid bacteria strain, Lactococcus lactis JCM 5805 (LC-Plasma), stimulated pDCs and prevented viral infection in mouse and human studies. Meanwhile, emulsifiers have recently been highlighted as candidate adjuvants for some viral vaccines and cancer immunotherapies. In this study, we discovered some specific emulsifiers, mainly consisting of sucrose fatty acid esters, that drastically enhance the potency of LC-Plasma to activate pDCs in vitro...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449898/targeted-therapy-of-brain-metastases-latest-evidence-and-clinical-implications
#9
REVIEW
Rodica Di Lorenzo, Manmeet S Ahluwalia
Brain metastases (BM) occur in 20-40% of patients with cancer and 60-75% of patients with BM become symptomatic. Due to an aging population and advances in the treatment of primary cancers, patients are living longer and are more likely to experience complications from BM. The diagnosis of BM drastically worsens long-term survival rates, with multiple metastases being a poor prognostic factor. Until recently, the mainstay of treatment consisted of stereotactic radiosurgery (SRS), surgical resection, whole brain radiation therapy (WBRT), or a combination of these modalities...
December 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/29448979/cd103-cd8-t-lymphocytes-in-non-small-cell-lung-cancer-are-phenotypically-and-functionally-primed-to-respond-to-pd-1-blockade
#10
Peiliang Wang, Bing Huang, Yi Gao, Jianjian Yang, Zhihui Liang, Ni Zhang, Xiangning Fu, Lequn Li
CD103 + CD8 + tumor infiltrating lymphocytes (TILs) have been linked to prolonged survival in various types of cancer including non-small cell lung cancer (NSCLC). However, the factors associated with the retention of CD103 + CD8 + TILs in lung cancer tissues remain largely unknown. Additionally, the contribution of CD103 + CD8 + TILs to effective PD-1 based immunotherapy has not been fully elucidated. In this study, we identified that the expression levels of E-cadherin and TGF-β were significantly correlated with the distribution and the density of CD103 + TILs in lung cancer tumor tissues...
February 7, 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29444918/immunotherapy-a-new-standard-of-care-in-thoracic-malignancies-a-summary-of-the-european-respiratory-society-research-seminar-of-the-thoracic-oncology-assembly
#11
Adrien Costantini, Marta Grynovska, Francesca Lucibello, Jorge Moisés, Franck Pagès, Ming S Tsao, Frances A Shepherd, Hasna Bouchaab, Marina Garassino, Joachim G J V Aerts, Julien Mazières, Michele Mondini, Thierry Berghmans, Anne-Pascale Meert, Jacques Cadranel
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events...
February 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/29441437/immune-checkpoint-blockade-the-new-frontier-in-cancer-treatment
#12
Jeffrey M Clarke, Daniel J George, Stacey Lisi, April K S Salama
Immune checkpoint blockers have revolutionized cancer treatment in recent years. These agents are now approved for the treatment of several malignancies, including melanoma, squamous and non-squamous non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck squamous cell carcinoma. Studies have demonstrated the significant impact of immunotherapy versus standard of care on patient outcomes, including durable response and extended survival. The use of immunotherapy-based combination therapy has been shown to further extend duration of response and survival...
February 13, 2018: Targeted Oncology
https://www.readbyqxmd.com/read/29440769/epithelial-mesenchymal-transition-emt-signature-is-inversely-associated-with-t-cell-infiltration-in-non-small-cell-lung-cancer-nsclc
#13
Young Kwang Chae, Sangmin Chang, Taeyeong Ko, Jonathan Anker, Sarita Agte, Wade Iams, Wooyoung M Choi, Kyoungmin Lee, Marcelo Cruz
Epithelial-mesenchymal transition (EMT) is able to drive metastasis during progression of multiple cancer types, including non-small cell lung cancer (NSCLC). As resistance to immunotherapy has been associated with EMT and immune exclusion in melanoma, it is important to understand alterations to T-cell infiltration and the tumor microenvironment during EMT in lung adenocarcinoma and squamous cell carcinoma. We conducted an integrated analysis of the immune landscape in NSCLCs through EMT scores derived from a previously established 16 gene signature of canonical EMT markers...
February 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29435295/identification-of-candidate-responders-for-anti-pd-l1-pd-1-immunotherapy-rova-t-therapy-or-ezh2-inhibitory-therapy-in-small-cell-lung-cancer
#14
Motonobu Saito, Katsuharu Saito, Kouya Shiraishi, Daichi Maeda, Hiroyuki Suzuki, Yoshihiro Minamiya, Koji Kono, Takashi Kohno, Akiteru Goto
A useful candidate for small-cell lung cancer (SCLC) therapy is immune checkpoint blockade therapy targeting programmed death-1 (PD-1) and its ligand, PD-L1. Furthermore, rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate, and enhancer of zeste homologue 2 (EZH2) inhibitor are expected to be the first targeted therapy for SCLC. The aim of the present study was to evaluate PD-L1, DLL3 and EZH2 expression in SCLCs to find a candidate responder to those therapies. Immunohistochemical (IHC) staining for PD-L1, DLL3 and EZH2 was performed in 20 patients with SCLC and the clinicopathological characteristics and IHC staining intensity were compared...
February 2018: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/29435172/promiximab-duocarmycin-a-new-cd56-antibody-drug-conjugates-is-highly-efficacious-in-small-cell-lung-cancer-xenograft-models
#15
Lin Yu, Ying Lu, Yuqin Yao, Yu Liu, Yuxi Wang, Qinhuai Lai, Ruirui Zhang, Wenting Li, Ruixue Wang, Yuyin Fu, Yiran Tao, Shuli Yi, Lantu Gou, Ligong Chen, Jinliang Yang
Small cell lung cancer (SCLC) is of a highly invasive and metastatic lung cancer subtype and there had not been effective targeted therapies. CD56, a cell surface marker highly expressed on most SCLC, is a promising therapeutic target for treatment of this aggressive cancer. In this study, we generated a novel anti-CD56 antibody named promiximab, characterized by high affinity, internalization and tumor specificity. Then, the promiximab was conjugated with a potent DNA alkylating agent duocarmycin via reduced interchain disulfides to yield the promiximab-Duocarmycin (promiximab-DUBA) conjugates...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435154/efficacy-of-granulocyte-macrophage-colony-stimulating-factor-combined-with-metronomic-paclitaxel-in-the-treatment-of-lewis-lung-carcinoma-transplanted-in-mice
#16
Nengping Zhu, Rongsheng Qin, Qin Zhang, Shaozhi Fu, Shanshan Liu, Yue Chen, Juan Fan, Yunwei Han
Metronomic chemotherapy in combination with immunotherapy is an attractive approach in cancer therapy. The purpose of the present study was to investigate the anti-tumor effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with metronomic paclitaxel (MET PTX) on Lewis lung carcinoma transplanted in mice. In the present study, tumor-bearing mice survival time and tumor growth were monitored. The day after the end of the treatment, white blood cells were counted, and the number and maturation of dendritic cell were determined by flow cytometry...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435109/clinical-and-molecular-features-of-innate-and-acquired-resistance-to-anti-pd-1-pd-l1-therapy-in-lung-cancer
#17
Shalin Shah, Kevin Wood, Brian Labadie, Brian Won, Ryan Brisson, Theodore Karrison, Thomas Hensing, Mark Kozloff, Riyue Bao, Jyoti D Patel, Jason J Luke
Hypothesis: The majority of non-small cell lung cancer (NSCLC) patients treated with anti-PD-1/PD-L1 therapy develop either innate or acquired resistance. Across tumor types, the "T cell-inflamed" tumor microenvironment correlates with clinical response to immunotherapy. We hypothesize that clinical characteristics may be predictive of resistance and that "T cell-inflamed" NSCLC tumors can be identified by gene expression profiling. Results: Of 93 patients, 36 (38...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29426340/pd-l1-diagnostic-tests-a-systematic-literature-review-of-scoring-algorithms-and-test-validation-metrics
#18
REVIEW
Margarita Udall, Maria Rizzo, Juliet Kenny, Jim Doherty, SueAnn Dahm, Paul Robbins, Eric Faulkner
BACKGROUND: The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer types express PD-L1 and evade immune recognition via the PD-1/PD-L1 interaction. Precision therapies targeting the PD-1/PD-L1 pathway have the potential to improve response and thereby offer a novel treatment avenue to some patients with cancer. However, this new therapeutic approach requires reliable methods for identifying patients whose cancers are particularly likely to respond...
February 9, 2018: Diagnostic Pathology
https://www.readbyqxmd.com/read/29425685/out-of-the-darkness-and-into-the-light-new-strategies-for-improving-treatments-for-locally-advanced-non-small-cell-lung-cancer
#19
Yun Zhang, Qin Lin, Ting Xu, Weiye Deng, Jinming Yu, Zhongxing Liao, Jinbo Yue
The standard treatment for locally advanced non-small cell lung cancer (LA NSCLC) includes surgery, radiotherapy, chemotherapy, or some combination of these modalities. Many clinical trials have been conducted in attempts to intensify treatment for LA NSCLC, but with little improvement. A therapeutic plateau had been reached, with no major progress in extending survival for patients with this disease. However, several recent trials of newer targeted therapies and immunotherapies may shed new light on potential therapeutic breakthroughs...
February 6, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29423109/hla-class-i-loss-and-pd-l1-expression-in-lung-cancer-impact-on-t-cell-infiltration-and-immune-escape
#20
Francisco Perea, Abel Sánchez-Palencia, Mercedes Gómez-Morales, Mónica Bernal, Ángel Concha, Míguela Méndez García, Amanda Rocío González-Ramírez, Martin Kerick, Javier Martin, Federico Garrido, Francisco Ruiz-Cabello, Natalia Aptsiauri
Immune-checkpoint inhibitors show encouraging results in cancer treatment, but the clinical benefit is limited exclusively to a subset of patients. We analyzed the density and composition of tumor T-cell infiltration in non-small-cell lung carcinoma (NSCLC) in relation to PD-L1 and HLA class I (HLA-I) expression. We found that positive HLA-I expression, independently on PD-L1 status, is the key factor determining the increased density of the immune infiltrate. When both markers were analyzed simultaneously, we identified four phenotypes of HLA-I and PD-L1 co-expression...
January 9, 2018: Oncotarget
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