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Immunotherapy for lung cancer

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https://www.readbyqxmd.com/read/29222126/autoimmune-crmp5-neuropathy-phenotype-and-outcome-defined-from-105-cases
#1
Divyanshu Dubey, Vanda A Lennon, Avi Gadoth, Sean J Pittock, Eoin P Flanagan, John E Schmeling, Andrew McKeon, Christopher J Klein
OBJECTIVE: To establish the phenotype and clinical outcomes of collapsin response-mediator protein-5 (CRMP5) autoimmune neuropathy in comparison with anti-neuronal nuclear antibody type 1 (ANNA1)-immunoglobulin G (IgG) neuropathy. METHODS: Patients with CRMP5-IgG and/or ANNA1-IgGs were identified in our service-line testing, and medical records were reviewed. RESULTS: One hundred five patients with CRMP5-IgG neuropathy (88% smokers; 69% having cancer, most commonly small cell lung cancer [75%]) were identified and compared to 51 patients with ANNA1-IgG neuropathy, 27 with coexisting CRMP5-IgG...
December 8, 2017: Neurology
https://www.readbyqxmd.com/read/29217732/peptide-blocking-of-pd-1-pd-l1-interaction-for-cancer-immunotherapy
#2
Chunlin Li, Nengpan Zhang, Jundong Zhou, Chen Ding, Yaqing Jin, Xueyuan Cui, Kefeng Pu, Yimin Zhu
Immunotherapy has become a promising alternative therapeutic approach for cancer patients. Interruption of immune checkpoints, such as CTLA-4 and PD-1, has been verified to be a successful means for cancer therapy in clinical trials. Monoclonal antibody (mAb) targeting to PD-L1 has been approved to treat urothelial carcinoma, non-small cell lung cancer or merkel cell carcinoma by the Food and Drug Administration (FDA). However, the high cost of the antibody can limit its application. In our study, TPP-1 (targeting PD-L1 peptide), which specifically binds to PD-L1 with high affinity, was identified through bacterial surface display methods...
December 7, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29213088/nsd1-inactivation-defines-an-immune-cold-dna-hypomethylated-subtype-in-squamous-cell-carcinoma
#3
Kevin Brennan, June Ho Shin, Joshua K Tay, Marcos Prunello, Andrew J Gentles, John B Sunwoo, Olivier Gevaert
Chromatin modifying enzymes are frequently mutated in cancer, resulting in widespread epigenetic deregulation. Recent reports indicate that inactivating mutations in the histone methyltransferase NSD1 define an intrinsic subtype of head and neck squamous cell carcinoma (HNSC) that features pronounced DNA hypomethylation. Here, we describe a similar hypomethylated subtype of lung squamous cell carcinoma (LUSC) that is enriched for both inactivating mutations and deletions in NSD1. The 'NSD1 subtypes' of HNSC and LUSC are highly correlated at the DNA methylation and gene expression levels, featuring ectopic expression of developmental transcription factors and genes that are also hypomethylated in Sotos syndrome, a congenital disorder caused by germline NSD1 mutations...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29212506/chromosome-9p-copy-number-gains-involving-pd-l1-are-associated-with-a-specific-proliferation-and-immune-modulating-gene-expression-program-active-across-major-cancer-types
#4
Jan Budczies, Carsten Denkert, Balázs Győrffy, Peter Schirmacher, Albrecht Stenzinger
BACKGROUND: Inhibition of the PD-L1/PD-1 immune checkpoint axis represents one of the most promising approaches of immunotherapy for various cancer types. However, immune checkpoint inhibition is successful only in subpopulations of patients emphasizing the need for powerful biomarkers that adequately reflect the complex interaction between the tumor and the immune system. Recently, recurrent copy number gains (CNG) in chromosome 9p involving PD-L1 were detected in many cancer types including lung cancer, melanoma, bladder cancer, head and neck cancer, cervical cancer, soft tissue sarcoma, prostate cancer, gastric cancer, ovarian cancer, and triple-negative breast cancer...
December 6, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/29209560/pd-l1-and-epithelial-mesenchymal-transition-in-circulating-tumor-cells-from-non-small-cell-lung-cancer-patients-a-molecular-shield-to-evade-immune-system
#5
Cristina Raimondi, Guido Carpino, Chiara Nicolazzo, Angela Gradilone, Walter Gianni, Alain Gelibter, Eugenio Gaudio, Enrico Cortesi, Paola Gazzaniga
The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understanding the events underlying tumor immune resistance. Although the expression of PD-L1 in tumor tissue has been correlated with clinical response to anti PD-1 inhibitors, the ability of this marker to discriminate the subgroup of patients who derive benefit from immunotherapy is suboptimal...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29209070/assessment-of-concordance-between-22c3-and-sp142-immunohistochemistry-assays-regarding-pd-l1-expression-in-non-small-cell-lung-cancer
#6
Haipeng Xu, Gen Lin, Cheng Huang, Weifeng Zhu, Qian Miao, Xirong Fan, Biao Wu, Xiaobing Zheng, Xiandong Lin, Kan Jiang, Dan Hu, Chao Li
Different anti-PD-1 and anti-PD-L1 antibodies bind different epitopes. However, whether the results from the SP142 and 22C3 immunochemistry (IHC) assays can be interchanged to determine patient eligibility for immunotherapy remains largely unknown. Histologic sections from 135 tumor samples were probed with both 22C3 and SP142 antibodies. The concordance of PD-L1 expression determined by the two assays was assessed. Additionally, we evaluated the association of PD-L1 expression detected by different assays with clinicopathological features and prognosis...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29207685/excellent-response-to-chemotherapy-post-immunotherapy
#7
Ashish D Dwary, Samip Master, Abhishek Patel, Constance Cole, Richard Mansour, Glenn Mills, Nebu Koshy, Prakash Peddi, Gary Burton, Dalia Hammoud, Kavitha Beedupalli
Introduction: Immunotherapy in the form of immune checkpoint inhibitors has changed the landscape of cancer treatment. Newer monoclonal antibodies are coming up and are being tested in various cancers during different stages of treatment. With the increasing use of immune checkpoint inhibitors in the management of various types of cancers, the question is raised as to what next can be offered to a patient who has progressed on this newer treatment. Does Sequence matter? There have been reports of improved responses to chemotherapy after immunotherapy in the form of vaccines...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207115/current-status-and-future-prospects-of-the-strategy-of-combining-car%C3%A2-t-with-pd%C3%A2-1-blockade-for-antitumor-therapy-review
#8
Jinjing Xu, Qing Zhang, Kang Tian, Haiyu Wang, Hong Yin, Junnian Zheng
The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients...
November 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29200112/epidemiology-treatment-and-complications-of-central-nervous-system-metastases
#9
Amy A Pruitt
PURPOSE OF REVIEW: Neurologic problems resulting from systemic cancer metastases to brain parenchyma, dura, spinal cord, and leptomeninges are among the most common types of consultations addressed by neurologists. With patients surviving longer from systemic cancer, along with the rapidly evolving therapeutic options, the treatment of these devastating complications has become both more effective and more complicated. This article reviews current patterns of metastatic disease and the increasingly nuanced landscape of evolving therapies, their complications, and their impact on quality of survival...
December 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/29200082/pneumonitis-in-irradiated-lungs-after-nivolumab-a-brief-communication-and-review-of-the-literature
#10
Farkhad Manapov, Olarn Roengvoraphoj, Maurice Dantes, Sebastian Marschner, Minglun Li, Chukwuka Eze
Nivolumab is a feasible therapy option in patients with advanced non-small cell lung cancer (NSCLC) who progress on first-line treatment. However, there is limited information about an overlapping toxicity of PD-1 inhibitors when administered following thoracic radiotherapy (TRT). Three of 25 patients with advanced NSCLC were treated with palliative or curative intent. Nivolumab was initiated as second or third-line therapy after TRT for recurrent or progressive disease. All 3 patients developed grade 3 pneumonitis at some point during nivolumab therapy...
December 1, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/29199595/epidermal-growth-factor-receptor-tyrosine-kinase-a-potential-target-in-treatment-of-non-small-cell-lung-carcinoma
#11
REVIEW
Venugopal Vinod Prabhu, Niranjali Devaraj
Lung cancer is responsible for 1.6 million deaths. Approximately 80%-85% of lung cancers are of the non-small-cell variety, which includes squamous cell carcinoma, adenocarcinoma, and large-cell carcinoma. Knowing the stage of cancer progression is a requisite for determining which management approach-surgery, chemotherapy, radiotherapy, and/or immunotherapy-is optimal. Targeted therapeutic approaches with antiangiogenic monoclonal antibodies or tyrosine kinase inhibitors are one option if tumors harbor oncogene mutations...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29198327/critical-features-and-challenges-associated-with-imaging-in-patients-undergoing-cancer-immunotherapy
#12
REVIEW
Cinzia Solinas, Michele Porcu, Zuzana Hlavata, Pushpamali De Silva, Marco Puzzoni, Karen Willard-Gallo, Mario Scartozzi, Luca Saba
Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29195578/programmed-death-cell-ligand-1-pd-l1-is-associated-with-survival-in-stage-i-non-small-cell-lung-cancer
#13
Boris Sepesi, Edwin Parra Cuentas, Jaime Rodriguez Canales, Carmen Behrens, Arlene M Correa, Ara Vaporciyan, Annikka Weissferdt, Neda Kalhor, Cesar Moran, Stephen Swisher, Ignacio Wistuba
Programmed cell death ligand (PD-L1) has been studied as a predictive immunotherapy biomarker. We investigated PD-L1 expression in the whole tumor and in tumor-infiltrating macrophages (TIMs) as a prognostic biomarker in surgically resected pathologic stage I non-small cell lung cancer. Pathologic specimen from 113 patients with stage I lung cancer (pT1-2a, N0, M0, tumor size 1-5 cm, 79 adenocarcinoma, 34 squamous cell carcinoma) were analyzed for PD-L1 expression in the tumor and in the TIMs using immunohistochemistry and image analysis...
2017: Seminars in Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/29195503/recent-development-in-clinical-applications-of-pd-1-and-pd-l1-antibodies-for-cancer-immunotherapy
#14
REVIEW
Bingshan Liu, Yongping Song, Delong Liu
Antibodies against programmed death (PD) pathway are revolutionizing cancer immunotherapy. Currently five antibodies against PD-1/PD-L1 have been approved. The clinical use of these antibodies is rapidly expanding. Incorporation of PD antibodies into chemotherapy regimens is in active clinical investigations. The combination of pembrolizumab with carboplatin and pemetrexed has been approved for the first line therapy of metastatic non-squamous non-small cell lung cancer. Combination of PD-1/PD-L1 antibodies with small molecule inhibitors such as tyrosine kinase inhibitors and IDO inhibitors are in active clinical trials...
December 1, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29194117/non-small-cell-lung-cancer-from-hiv-infected-patients-expressed-pd-l1-with-marked-inflammatory-infiltrates
#15
Charlotte Domblides, Martine Antoine, Cécile Hamard, Nathalie Rabbe, Anita Rodenas, Thibault Vieira, Perrine Crequit, Jacques Cadranel, Armelle Lavolé, Marie Wislez
OBJECTIVE: Immunotherapy techniques targeting the programmed cell death protein 1 (PD-1) to PD ligand 1 (PD-L1) checkpoint have improved prognosis in lung cancer. PD-1/PD-L1 status, however, has not been investigated in human immunodeficiency virus (HIV)-positive patients. This study sought to assess PD-L1 status and tumor immune-cell infiltration in non-small cell lung cancer (NSCLC) in HIV patients. METHODS: All consecutive HIV patients treated for NSCLC between 1996 and 2014 were enrolled...
November 30, 2017: AIDS
https://www.readbyqxmd.com/read/29194007/product-review-on-the-anti-pd-l1-antibody-atezolizumab
#16
Neil J Shah, William J Kelly, Stephen V Liu, Karin Choquette, Alexander Spira
Immunotherapy as a therapeutic strategy has seized the narrative throughout clinical oncology over the past few years. Once considered a niche treatment for rare cancers, immunotherapy has quickly emerged as the standard of care for many common cancer types. The remarkable rise is largely due to the development of novel checkpoint inhibitors, specifically, antibodies targeting PD-1 and PD-L1. Offering promising efficacy with a favorable toxicity profile, these agents have been approved for use in several malignancies and are under investigation for many more...
December 1, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29191606/response-rates-to-single-agent-chemotherapy-after-exposure-to-immune-checkpoint-inhibitors-in-advanced-non-small-cell-lung-cancer
#17
Gustavo Schvartsman, S Andrew Peng, Giorgios Bis, J Jack Lee, Marcelo F K Benveniste, Jianjun Zhang, Emily B Roarty, Lara Lacerda, Stephen Swisher, John V Heymach, Frank V Fossella, William N William
INTRODUCTION: Exploratory analysis of clinical trials in various tumor types have demonstrated potential improvements in overall response rate (ORR) to chemotherapy after exposure to vaccine-based immunotherapy. The objective of this retrospective study was to determine if single-agent chemotherapy (3rd-line or beyond) would yield improved ORR when given after exposure to programmed death-(ligand)1 inhibitors (anti-PD1) in metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We queried the Thoracic GEMINI database of MD Anderson Cancer Center for patients treated between 06/12 and 11/16 who received at least one single-agent chemotherapy as 3rd-line or beyond, following progression after platinum-based chemotherapy and anti-PD1...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29191604/mhc-class-ii-expression-in-lung-cancer
#18
Yayi He, Leslie Rozeboom, Christopher J Rivard, Kim Ellison, Rafal Dziadziuszko, Hui Yu, Caicun Zhou, Fred R Hirsch
BACKGROUND: Immunotherapy is an exciting development in lung cancer research. In this study we described major histocompatibility complex (MHC) Class II protein expression in lung cancer cell lines and patient tissues. METHODS: We studied MHC Class II (DP, DQ, DR) (CR3/43, Abcam) protein expression in 55 non-small cell lung cancer (NSCLC) cell lines, 42 small cell lung cancer (SCLC) cell lines and 278 lung cancer patient tissues by immunohistochemistry (IHC). RESULTS: Seven (12...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29191596/pd-l1-expression-in-advanced-nsclc-insights-into-risk-stratification-and-treatment-selection-from-a-systematic-literature-review
#19
REVIEW
Robert Brody, Yiduo Zhang, Marc Ballas, Mohd Kashif Siddiqui, Palvi Gupta, Craig Barker, Anita Midha, Jill Walker
Tumors can evade immune detection by exploiting inhibitory immune checkpoints such as the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathway. Antibodies that block this pathway offer a promising new approach to treatment in advanced/metastatic non-small cell lung cancer (NSCLC). A systematic review of the literature was conducted to assess the association of PD-L1 with important patient and disease characteristics, the prognostic significance of PD-L1 expressing NSCLC tumors, and the value of PD-L1 as a predictive biomarker of response to anti-PD-1/PD-L1 treatments in advanced/metastatic NSCLC...
October 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29187357/iap-antagonists-enhance-cytokine-production-from-mouse-and-human-inkt-cells
#20
Eleanor Clancy-Thompson, Lestat Ali, Patrick T Bruck, Mark A Exley, Richard S Blumberg, Glenn Dranoff, Michael Dougan, Stephanie K Dougan
Inhibitor of apoptosis protein (IAP) antagonists are in clinical trials for a variety of cancers, and mouse models show synergism between IAP antagonists and anti-PD-1 immunotherapy. Although IAP antagonists affect the intrinsic signaling of tumor cells, their most pronounced effects are on immune cells and the generation of antitumor immunity. Here we examined the effects of IAP antagonism on T-cell development using mouse fetal thymic organ culture and observed a selective loss of iNKT cells, an effector cell type of potential importance for cancer immunotherapy...
November 29, 2017: Cancer Immunology Research
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