Read by QxMD icon Read

pd1 AND lung cancer

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
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
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
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
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
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
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
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
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
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
Alok Mishra, Mukesh Verma
Utilizing biology of PD-1: PD-L1 interaction related pathways for cancer immunotherapy is an emerging concept in cancer research. However, there is limited literature on epigenetic regulation of PD1 gene (PDCD1). Promising data from clinical trials of PD/PDl-1 immunotherapy in melanoma, renal cancers, colorectal and lung cancers has generated a lot of hope for successful treatment of patients. Immunotherapy in cancers has a significant role in strategizing NCI's Cancer Moonshot Program of US NIH and FDA policies...
2018: Methods in Molecular Biology
Rilan Bai, Naifei Chen, Jiuwei Cui
In recent years, epidermal growth factor receptor tyrosine kinase inhibitors have been recommended by many guidelines as first-line drugs for advanced non-small cell lung cancer (NSCLC) with EGFR gene mutations and no resistance. However, with the prolongation of medication time, most appear acquired resistance. In recent years, breakthroughs in inhibitors of programmed death-1 (PD-1) and its ligand (PD1 ligand, PD-L1) have rapidly changed the therapeutic model of NSCLC. Recent studies have shown that the efficacy of immune checkpoint inhibitors in EGFR-mutant NSCLC patients is not satisfactory, which might be caused by low PD-L1 expression, inhibitory immune microenvironment and low tumor mutation load...
August 20, 2018: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Myra O Villareal, Yuki Sato, Kyoko Matsuyama, Hiroko Isoda
BACKGROUND: Melanoma is one of the most invasive and aggressive types of cancer with a very poor prognosis. Surgery remains the most efficient treatment prior melanoma invasion and metastasis formation. However, therapy becomes a challenge once the cancer cells colonized other tissues. At present, there are two main classes of therapies acting with a certain efficiency on metastatic melanoma: immune check point inhibitors (anti-PD1/PDL1) and targeted therapy such as Vemurafenib. Unfortunately, these therapies are not fully responsive, induce resistance and/or generate unwanted side effects...
August 29, 2018: BMC Cancer
David A Fabrizio, Thomas J George, Richard F Dunne, Garrett Frampton, James Sun, Kyle Gowen, Mark Kennedy, Joel Greenbowe, Alexa B Schrock, Aram F Hezel, Jeffrey S Ross, Phillip J Stephens, Siraj M Ali, Vincent A Miller, Marwan Fakih, Samuel J Klempner
Background: The clinical application of PD1/PD-L1 targeting checkpoint inhibitors in colorectal cancer (CRC) has largely focused on a subset of microsatellite instable (MSI-high) patients. However, the proposed genotype that sensitizes these patients to immunotherapy is not captured by MSI status alone. Estimation of tumor mutational burden (TMB) from comprehensive genomic profiling is validated against whole exome sequencing and linked to checkpoint response in metastatic melanoma, urothelial bladder cancer and non-small cell lung carcinoma...
August 2018: Journal of Gastrointestinal Oncology
Keith E Steele, Charles Brown
Multiplex immunohistochemistry allows the demonstration of multiple protein antigens in individual histological sections of formalin-fixed paraffin-embedded tumors or other types of tissue. Carefully designed and optimized immunohistochemistry (IHC) assays not only maximize the information available from limited tissues, but also enable a higher level interpretation of that information by demonstrating the histo-anatomical relationships among key cell types which express the included biomarkers. Programmable automated IHC instruments support the development and application of complicated multiplex IHC protocols, help save time and effort, and enhance immunostaining quality and reproducibility...
2018: Methods in Molecular Biology
Nataly Manjarrez-Orduño, Laurence C Menard, Selena Kansal, Paul Fischer, Bijal Kakrecha, Can Jiang, Mark Cunningham, Danielle Greenawalt, Vishal Patel, Minghui Yang, Ryan Golhar, Julie A Carman, Sergey Lezhnin, Hongyue Dai, Paul S Kayne, Suzanne J Suchard, Steven H Bernstein, Steven G Nadler
Agents targeting the PD1-PDL1 axis have transformed cancer therapy. Factors that influence clinical response to PD1-PDL1 inhibitors include tumor mutational burden, immune infiltration of the tumor, and local PDL1 expression. To identify peripheral correlates of the anti-tumor immune response in the absence of checkpoint blockade, we performed a retrospective study of circulating T cell subpopulations and matched tumor gene expression in melanoma and non-small cell lung cancer (NSCLC) patients. Notably, both melanoma and NSCLC patients whose tumors exhibited increased inflammatory gene transcripts presented high CD4+ and CD8+ central memory T cell (CM) to effector T cell (Eff) ratios in blood...
2018: Frontiers in Immunology
Muhammad Khan, Jie Lin, Guixiang Liao, Yunhong Tian, Yingying Liang, Rong Li, Mengzhong Liu, Yawei Yuan
BACKGROUND: Recently, immune checkpoint inhibitors have shown survival advantage over chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). This meta-analysis was conducted to gather and analyze the available evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD-L1) therapies and chemotherapy in the treatment of advanced NSCLC. METHODS: A search strategy was devised to identify the randomized controlled trials (RCTs) using electronic databases of PubMed, Cochrane Library, and Web of Science...
August 2018: Medicine (Baltimore)
Sebastian Kobold, Stanislav Pantelyushin, Felicitas Rataj, Johannes Vom Berg
T cells have been established as core effectors for cancer therapy; this has moved the focus of therapeutic endeavors to effectively enhance or restore T cell tumoricidal activity rather than directly target cancer cells. Both antibodies targeting the checkpoint inhibitory molecules programmed death receptor 1 (PD1), PD-ligand 1 (PD-L1) and cytotoxic lymphocyte activated antigen 4 (CTLA4), as well as bispecific antibodies targeting CD3 and CD19 are now part of the standard of care. In particular, antibodies to checkpoint molecules have gained broad approval in a number of solid tumor indications, such as melanoma or non-small cell lung cancer based on their unparalleled efficacy...
2018: Frontiers in Oncology
Weijing Cai, Dapeng Zhou, Weibo Wu, Wen Ling Tan, Jiaqian Wang, Caicun Zhou, Yanyan Lou
BACKGROUND: Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody. RESULTS: In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules...
August 3, 2018: BMC Genomics
Olivier Bylicki, Nicolas Paleiron, Gaëlle Rousseau-Bussac, Christos Chouaïd
The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naïve metastatic NSCLC with ≥50% of tumor cells expressing PDL1 and for metastatic NSCLC with ≥1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy...
2018: OncoTargets and Therapy
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"