Programmed cell death ( PD-1 )

Yuichiro Yamamoto, Masatoshi Kakizaki, Takayuki Shimizu, Joaquim Carreras, Tetsuhiro Chiba, Kenji Chamoto, Tatehiro Kagawa, Taku Aoki, Naoya Nakamura, Kiyoshi Ando, Ai Kotani
Chronic hepatitis B is now controllable when treated with nucleoside reverse transcriptase inhibitors (NRTIs), which inhibit hepatitis B virus (HBV) replication. However, once the NRTIs are discontinued, most patients relapse, necessitating lifelong NRTIs treatment. HBV infection relapse is assumed to be caused by the persistent existence of covalently closed circular DNA in the nuclei of infected hepatocytes. The mechanism by which covalently closed circular DNA-positive hepatocytes escape immune surveillance during NRTIs treatment remains elusive...
March 27, 2020: International Immunology
Qingxian Wen, Tao Han, Zijian Wang, Shulong Jiang
Immune escape plays a vital role in the development of liver cancer. The interaction between programmed death-ligand 1 (PD-L1) and programmed cell death-1 is a key mediator of cancer immune escape, which leads to the suppression of anticancer immunity and promotion of tumor progression. Hypoxia is a common phenomenon in the tumor microenvironment. Under hypoxic conditions, suppressive immune cells, such as regulatory T cells, myeloid-derived suppressor cells and M2 macrophages, are frequently recruited to tumor tissues to form the immunosuppressive microenvironment in liver cancer...
April 2020: Oncology Letters
Akitaka Fujita, Keiko Kan-O, Ken Tonai, Norio Yamamoto, Tomohiro Ogawa, Satoru Fukuyama, Yoichi Nakanishi, Koichiro Matsumoto
Viral infections of the airway can exacerbate respiratory diseases, such as asthma or chronic obstructive pulmonary disease (COPD), and accelerate disease progression. Phosphoinositide 3-kinase (PI3K)δ, a class 1A PI3K, has been studied as a potential target for achieving anti-oncogenic and anti-inflammatory effects. However, the role of PI3Kδ in antiviral responses is poorly understood. Using a synthetic double-stranded RNA poly I:C and a selective PI3Kδ inhibitor IC87114, we investigated the role of PI3Kδ signaling in poly I:C-induced expression of the T lymphocyte-inhibitory molecule programmed death 1 ligand 1 (PD-L1), inflammatory responses and antiviral interferon (IFN) responses...
2020: Frontiers in Immunology
Jonathan Rios-Doria, Christina Stevens, Christopher Maddage, Kerri Lasky, Holly K Koblish
BACKGROUND: Preclinical evaluation of drugs targeting the human immune system has posed challenges for oncology researchers. Since the commercial introduction of humanized mice, antitumor efficacy and pharmacodynamic studies can now be performed with human cancer cells within mice bearing components of a human immune system. However, development and characterization of these models is necessary to understand which model may be best suited for different agents. METHODS: We characterized A375, A549, Caki-1, H1299, H1975, HCC827, HCT116, KU-19-19, MDA-MB-231, and RKO human cancer cell xenografts in CD34+ humanized non-obese diabetic-scid gamma mice for tumor growth rate, immune cell profiling, programmed death ligand 1 (PD-L1) expression and response to anti-PD-L1 therapy...
March 2020: Journal for Immunotherapy of Cancer
Isnard Elman Litvin, Machline Paim Paganella, Eliana Marcia Wendland, Adriana Vial Roehe
BACKGROUND: Breast cancer is one of the most common malignancies in women worldwide, and one of the leading causes of cancer-related death. Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key physiologic suppressors of the cytotoxic immune reaction. Some authors advocate that PD-L1 expression may help in breast cancer prognosis. METHODS: We will conduct a systematic review of observational or interventional studies evaluating the prognostic ability of PD-L1 expression levels in predicting positive clinical outcomes in Human Breast Cancer...
March 26, 2020: Systematic Reviews
Justin A Chen, Weijie Ma, Jianda Yuan, Tianhong Li
Immune checkpoint inhibitors (ICIs) targeting the programed cell-death protein 1 (PD-1) or its ligand PD-L1 and cytotoxic T-lymphocyte antigen 4 (CTLA-4) pathways have improved the survival for patients with solid tumors. Unfortunately, durable clinical responses are seen in only 10-40% of patients at the cost of potential immune-related adverse events. In the tumor microenvironment (TME), tumor cells can influence the microenvironment by releasing extracellular signals and generating peripheral immune tolerance, while the immune cells can affect the initiation, growth, proliferation, and evolution of cancer cells...
2020: Cancer Treatment and Research
Yu Hei, Binhong Teng, Ziqian Zeng, Siqi Zhang, Qian Li, Jijia Pan, Zuyuan Luo, Chunyang Xiong, Shicheng Wei
Background: Immune checkpoint blockades (ICBs) are a promising treatment for cancers such as melanoma by blocking important inhibitory pathways that enable tumor cells to evade immune attack. Programmed death ligand 1 monoclonal antibodies (aPDL1s) can be used as an ICB to significantly enhance the effectiveness of tumor immunotherapy by blocking the PD-1/PD-L1 inhibitory pathway. However, the effectiveness of aPDL1s may be limited by low selectivity in vivo and immunosuppressed tumor microenvironment including hypoxia...
2020: International Journal of Nanomedicine
Constance J Martin, Abhishek Datta, Christopher Littlefield, Ashish Kalra, Christopher Chapron, Stefan Wawersik, Kevin B Dagbay, Christopher T Brueckner, Anastasia Nikiforov, Francis T Danehy, Frederick C Streich, Christopher Boston, Allison Simpson, Justin W Jackson, Susan Lin, Nicole Danek, Ryan R Faucette, Pichai Raman, Allan D Capili, Alan Buckler, Gregory J Carven, Thomas Schürpf
Despite breakthroughs achieved with cancer checkpoint blockade therapy (CBT), many patients do not respond to anti-programmed cell death-1 (PD-1) due to primary or acquired resistance. Human tumor profiling and preclinical studies in tumor models have recently uncovered transforming growth factor-β (TGFβ) signaling activity as a potential point of intervention to overcome primary resistance to CBT. However, the development of therapies targeting TGFβ signaling has been hindered by dose-limiting cardiotoxicities, possibly due to nonselective inhibition of multiple TGFβ isoforms...
March 25, 2020: Science Translational Medicine
Eriko Miyawaki, Haruyasu Murakami, Keita Mori, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Hirotsugu Kenmotsu, Tateaki Naito, Toshiaki Takahashi
Epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer is less likely to express programmed death-ligand 1 (PD-L1) than tumors with wild-type EGFR and is associated with poor response to pembrolizumab. To understand the relationship between EGFR mutation and PD-L1 expression in pembrolizumab response, we retrospectively evaluated the factors contributing to the high tumor proportion score in 155 EGFR-mutant non-small cell lung cancer cases and their associated response to pembrolizumab. Uncommon EGFR mutations were significantly associated with a PD-L1 tumor proportion score ≥ 50% compared to common EGFR mutations...
March 25, 2020: Japanese Journal of Clinical Oncology
Akiko Ishii, Minato Yokoyama, Hiroshi Tsuji, Yasuhisa Fujii, Akira Tamaoka
Pembrolizumab is an immune checkpoint inhibitor (ICI) that targets the programmed cell death (PD)-1 receptor. It significantly increases the overall survival in patients with locally advanced or metastatic urothelial cancer. However, its administration may induce serious immune-related adverse effects, such as myocarditis and myasthenia gravis (MG). Therefore, ICI treatment may have been withheld for MG patients with cancer. We report the first case in which pembrolizumab was used safely without aggravation of MG symptoms in right renal pelvic and bladder cancers, even though the anti-acetylcholine receptor antibody (anti-ACh-R Ab) serum concentration increased...
June 2020: ENeurologicalSci
Yu Liu, Jingjing Ma, Yuqi Yang, Lin Liu, Guannan Zhu, Xiaoxia Wang, Shiyu Wang, Weinan Guo, Qiao Yue, Tao Zhao, Chunying Li, Tianwen Gao, Qiong Shi
<strong>BACKGROUND</strong> Melanoma is among the most aggressive forms of cancer. Our latest retrospective analysis showed that recombinant human interferon-alpha1b (IFN-alpha1b) led to significantly prolonged survival with mild toxicity in patients with stage IV melanoma. Based on this clinical finding, the current study sought to investigate the influence of IFN-alpha1b on the antitumor immunity of melanoma, with interferon-alpha2b (IFN-alpha2b) used as a control. <strong>MATERIAL AND METHODS</strong> Peripheral blood mononuclear cells were stimulated with culture medium alone, or medium supplemented with IFN-alpha1b or IFN-alpha2b...
March 14, 2020: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Hui Zhao, Jianhua Chen
BACKGROUND: Lymphoepithelioma-like carcinoma, an uncommon epithelial tumor, is mostly originated form the nasopharynx and also occurs in foregut-derived organs, such as lung, stomach, salivary gland, and thymus. Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare subtype accounting for around 0.9% of non-small cell lung cancer (NSCLC). We aimed to evaluate clinicopathological features, treatment modalities, and prognosis of PPLELC. METHODS: In the current study, a retrospective analysis on 8 patients diagnosed with PPLELC at Hunan Cancer Hospital between October 2013 and June 2016 was conducted with respect to their clinical characteristics and outcomes, in order to deeply investigate this rare subtype of lung cancer...
March 20, 2020: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Haiyue Ma, Jia Jia, Huiqin Guo, Huan Zhao, Cong Wang, Linlin Zhao, Yue Sun, Weihua Li, Zhihui Zhang
BACKGROUND: Pembrolizumab, an immunotherapy for advanced non-small cell lung cancer (NSCLC), needs to predict treatment response based on test results including immunohistochemistry (IHC), which detects the expression of programmed death ligand 1 (PD-L1). The aim of this study was to evaluate the feasibility of immunocytochemistry (ICC) in NSCLC cytology to detect PD-L1 and to investigate the correlation between PD-L1 expression and clinical pathology and molecular features. METHODS: Sixty cases of lung adenocarcinoma pleural cytology were collected and PD-L1 sp263 reagent was used for immunocytochemical staining according to the manufacturer's instructions...
March 20, 2020: Zhongguo Fei Ai za Zhi, Chinese Journal of Lung Cancer
Michael Benzaquen
Regarding the rising incidence and the not negligible mortality, the treatment of cutaneous squamous-cell carcinoma (cSCC) has a high clinical relevance. Immune checkpoint inhibitors (ICI), especially anti-programmed cell death-1 receptor (anti-PD-1) antibodies such as pembrolizumab and cemiplimab have shown promising results in phase 2 studies for patients with locally advanced and/or metastatic cSCC. We are presenting a review of the latest results in the treatment of cSCC with ICI. Patients with locally advanced or metastatic cSCC have been treated with cemiplimab 3 mg/kg every 2 weeks...
March 24, 2020: Dermatologic Therapy
Miwa Noda, Takaaki Masuda, Shuhei Ito, Taro Tobo, Akihiro Kitagawa, Qingjiang Hu, Dai Shimizu, Hidetoshi Eguchi, Tsuyoshi Etoh, Shinji Ohno, Masafumi Inomata, Koshi Mimori
BACKGROUND: Programmed cell death 1 (PD-1) inhibitors have shown significant therapeutic promise in various cancers. However, the clinical significance of PD-1 expression remains not fully understood. In this study, we evaluated the clinical and prognostic relevance of PD-1 expression in breast cancer (BC). METHODS: First, we analyzed PD-1 mRNA expression in BC tissues and performed a survival analysis using a dataset from The Cancer Genome Atlas. Next, we measured PD-1 mRNA expression in peripheral blood (PB) in BC patients by quantitative reverse-transcription polymerase chain reaction...
March 21, 2020: Annals of Surgical Oncology
Qianqian Ni, Fuwu Zhang, Yijing Liu, Zhantong Wang, Guocan Yu, Brian Liang, Gang Niu, Ting Su, Guizhi Zhu, Guangming Lu, Longjiang Zhang, Xiaoyuan Chen
Neoantigen vaccines have been enthusiastically pursued for personalized cancer immunotherapy while vast majority of neoantigens have no or low immunogenicity. Here, a bi-adjuvant neoantigen nanovaccine (banNV) that codelivered a peptide neoantigen (Adpgk) with two adjuvants [Toll-like receptor (TLR) 7/8 agonist R848 and TLR9 agonist CpG] was developed for potent cancer immunotherapy. Specifically, banNVs were prepared by a nanotemplated synthesis of concatemer CpG, nanocondensation with cationic polypeptides, and then physical loading with hydrophobic R848 and Adpgk...
March 2020: Science Advances
Chennianci Zhu, Weihao Zhuang, Limin Chen, Wenyu Yang, Wen-Bin Ou
Non-small-cell lung cancer (NSCLC), a main subtype of lung cancer, is one of the most common causes of cancer death in men and women worldwide. Circulating tumor DNA (ctDNA), tyrosine kinase inhibitors (TKIs) and immunotherapy have revolutionized both our understanding of NSCLC, from its diagnosis to targeted NSCLC therapies, and its treatment. ctDNA quantification confers convenience and precision to clinical decision making. Furthermore, the implementation of TKI-based targeted therapy and immunotherapy has significantly improved NSCLC patient quality of life...
February 2020: Translational Lung Cancer Research
Ruochen Li, Hao Liu, Yifan Cao, Jieti Wang, Yifan Chen, Yangyang Qi, Kunpeng Lv, Xin Liu, Kuan Yu, Chao Lin, Heng Zhang, Hongyong He, He Li, Lingli Chen, Zhenbin Shen, Jing Qin, Weijuan Zhang, Yihong Sun, Jiejie Xu
BACKGROUND: Intratumoural CD103+ CD8+ T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103+ CD8+ T cells in gastric cancer remains unexplored. METHODS: Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103+ CD8+ T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103+ CD8+ T cells was evaluated with the use of an in vitro study based on fresh tumour tissues...
March 24, 2020: British Journal of Cancer
ChangYin Feng, YingYing Zhang, JianPing Huang, QiaoLing Zheng, YingHong Yang, BenHua Xu
PURPOSE: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a recently discovered protein that is considered important in causing mutations in tumor cell genome bases. Whether APOBEC3B is expressed in nasopharyngeal carcinoma (NPC) still remains unknown. Studies have shown that programmed-cell-death receptor-1 ligand (PD-L1) is highly expressed in NPC, but its clinical significance has not been fully elucidated. We aimed to evaluate APOBEC3B and PD-L1 protein expression in NPC and also investigate their prognostic significance...
March 20, 2020: Applied Immunohistochemistry & Molecular Morphology: AIMM
Taichi Miyawaki, Hirotsugu Kenmotsu, Keita Mori, Eriko Miyawaki, Nobuaki Mamesaya, Takahisa Kawamura, Haruki Kobayashi, Shota Omori, Kazushige Wakuda, Akira Ono, Tateaki Naito, Haruyasu Murakami, Hideyuki Harada, Masahiro Endo, Yasuhisa Ohde, Kazuhisa Takahashi, Toshiaki Takahashi
BACKGROUND: Programmed cell death 1 (PD-1) inhibitors have become a standard treatment, albeit not completely effective, for patients with advanced non-small-cell lung cancer (NSCLC). Previous studies of advanced melanoma have revealed that the tumor burden predicted the response to PD-1 inhibitors, although this relationship has remained unclear for NSCLC. PATIENTS AND METHODS: The present single-center retrospective study evaluated 163 patients with advanced NSCLC who had received PD-1/programmed cell death ligand 1 (PD-L1) inhibitor monotherapy from December 2015 to December 2018...
February 26, 2020: Clinical Lung Cancer
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