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PD-L1 Cancer

Tianqun Lang, Yiran Liu, Zhong Zheng, Wei Ran, Yihui Zhai, Qi Yin, Pengcheng Zhang, Yaping Li
Metastatic breast cancer may be resistant to chemo-immunotherapy due to the existence of cancer stem cells (CSC). And the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti-CSC agent thioridazine (THZ), and the PD-1/PD-L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure...
December 5, 2018: Advanced Materials
Viswanath Gunda, Benjamin Gigliotti, Tameem Ashry, Dorothy Ndishabandi, Michael McCarthy, Zhiheng Zhou, Salma Amin, Kyu Eun Lee, Tabea Stork, Lori Wirth, Gordon J Freeman, Alessandro Alessandrini, Sareh Parangi
Patients with anaplastic thyroid cancer (ATC) have an extremely poor prognosis despite multimodal therapy with surgery and chemoradiation. Lenvatinib, a multi-targeted tyrosine kinase inhibitor, and checkpoint inhibitors targeting the programmed cell death pathway have proven effective in some patients with advanced thyroid cancer. Combination of these therapies is a potential means to boost effectiveness and minimize treatment resistance in ATC. We utilized our novel immunocompetent murine model of orthotopic ATC to demonstrate that lenvatinib led to significant tumor shrinkage and increased survival, while combination therapy led to dramatic improvements in both...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Min Huang, M Catherine Pietanza, Ayman Samkari, James Pellissier, Thomas Burke, Sheenu Chandwani, Fansen Kong, A Simon Pickard
OBJECTIVES: Pembrolizumab monotherapy showed significantly longer overall survival and fewer treatment-related adverse events compared to chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1)-positive tumors in the first-line setting in KEYNOTE (KN)-024 and in those previously treated in KN010. The objective of this analysis was to assess the benefit-risk of pembrolizumab in terms of quality-adjusted survival amongst patients in these trials...
December 4, 2018: PharmacoEconomics
Toshihiko Doi, Satoru Iwasa, Kei Muro, Taroh Satoh, Shuichi Hironaka, Taito Esaki, Tomohiro Nishina, Hiroki Hara, Nozomu Machida, Yoshito Komatsu, Yasuhiro Shimada, Satoshi Otsu, Shin Shimizu, Morihiro Watanabe
BACKGROUND: Avelumab is a human anti-PD-L1 IgG1 monoclonal antibody that has shown antitumor activity in several advanced cancers. We report results from JAVELIN Solid Tumor JPN, a phase 1 trial of avelumab in Japanese patients with advanced solid tumors with expansion in patients with advanced gastric cancer/gastroesophageal junction cancer. METHODS: In the dose-escalation part, eligible patients had various previously treated metastatic or advanced solid tumors...
December 4, 2018: Gastric Cancer
Haoran Zha, Xinxin Wang, Ying Zhu, Dian-Gang Chen, Xiao Han, Fei Yang, Jianbao Gao, Chunyan Hu, Chi Shu, Yi Feng, Yulong Tan, Jinyu Zhang, Yongsheng Li, Yisong Y Wan, Bo Guo, Bo Zhu
Complement aids in the construction of an immunosuppressive tumor microenvironment (TME). Tumor cell-derived C3 has been previously reported, but whether and how it acts on antitumor immunity remains to be elucidated. Here, we describe a mechanism for tumor cell-derived C3 in suppressing antitumor immunity. Tumor cell-derived C3 was activated intracellularly, which results in generation of C3a. C3a modulated tumor-associated macrophages (TAMs) via C3a-C3aR-PI3Kγ signaling, thereby repressing antitumor immunity...
December 4, 2018: Cancer Immunology Research
Tong Wu, Fei Zhou, Adiilah K Soodeen-Lalloo, Xing Yang, Yingran Shen, Xi Ding, Jinpeng Shi, Jie Dai, Jingyun Shi
OBJECTIVES: Programmed death-ligand 1 (PD-L1) expression might serve as a predictive biomarker for immune checkpoint inhibitors in lung cancer. However, the relationship between PD-L1 expression and imaging features of lung cancer has not been fully understood. PATIENTS AND METHODS: A total of 350 patients with pathologically confirmed adenocarcinoma who received surgical treatment and had preoperative thin section computed tomography (CT) examination were included...
November 14, 2018: Clinical Lung Cancer
Takahiro Nakagomi, Taichiro Goto, Yosuke Hirotsu, Daichi Shikata, Yujiro Yokoyama, Rumi Higuchi, Sotaro Otake, Kenji Amemiya, Toshio Oyama, Hitoshi Mochizuki, Masao Omata
Pulmonary invasive mucinous adenocarcinoma (IMA) is considered a variant of lung adenocarcinomas based on the current World Health Organization classification of lung tumors. However, the molecular mechanism driving IMA development and progression is not well understood. Thus, we surveyed the genomic characteristics of IMA in association with immune-checkpoint expression to investigate new potential therapeutic strategies. Tumor cells were collected from surgical specimens of primary IMA, and sequenced to survey 53 genes associated with lung cancer...
November 30, 2018: Cancers
Weihua Hou, Qingyun Yuan, Xingxing Yuan, Yuxiong Wang, Wei Mo, Huijie Wang, Min Yu
Background Redirecting T cells to tumor cells using bispecific antibodies (BsAbs) is emerging as a potent cancer therapy. The main concept of this strategy is to cross-link tumor cells and T cells by simultaneously binding to cell surface tumor-associated antigen (TAA) and the CD3ƹ chain. However, immune checkpoint programmed cell death ligand-1 (PD-L1) on tumor cells or other myeloid cells upreglulated remarkablely after the treatment of CD3-binding BsAbs, leads to the generation of suppressed microenvironment for immune evasion and tumor progression...
December 4, 2018: Investigational New Drugs
Yaxiong Zhang, Huaqiang Zhou, Li Zhang
Recent randomized phase III trials (KEYNOTE-407 and IMpower131) reported that adding anti-programmed death (ligand) 1 (anti-PD-(L)1) antibodies in combination with taxane-platinum improve the therapeutic efficacy for advanced squamous non-small-cell lung cancer (NSCLC). However, there is no head-to-head comparison of pembrolizumab (anti-PD-1) plus chemotherapy vs. atezolizumab (anti-PD-L1) plus chemotherapy. Therefore, we performed an indirect comparison to explore the optimal choice of anti-PD-(L)1 treatment for advanced squamous NSCLC in combination with chemotherapy...
December 3, 2018: Journal for Immunotherapy of Cancer
Jing Huang, Hongnan Mo, Weilong Zhang, Xuelian Chen, Dong Qu, Xi Wang, Dawei Wu, Xingyuan Wang, Bo Lan, Beibei Yang, Pei Wang, Bo Zhang, Qing Yang, Yuchen Jiao, Binghe Xu
BACKGROUND: The clinical response to anti-programmed cell death 1 (PD-1) antibodies in patients with advanced gastric and gastroesophageal junction (GEJ) cancer in China has not been reported. METHODS: This study evaluated the efficacy and safety of SHR-1210, an anti-PD-1 antibody, in patients with advanced gastric/GEJ cancer in a phase 1 trial. The associations between candidate biomarkers (programmed death ligand 1 [PD-L1] expression, mismatch repair status, tumor mutation load, and lactate dehydrogenase [LDH] levels) and the efficacy of SHR-1210 were also explored...
December 3, 2018: Cancer
Yang Du, Yinhua Jin, Wei Sun, Junjie Fang, Jianjun Zheng, Jie Tian
OBJECTIVES: This review describes the current status and progress of immune checkpoint targets for imaging of malignancies. Immune checkpoint blockade holds great potential for cancer treatment, and clinical implementation into routine is very rapidly progressing. Therefore, it is an urgent need to become familiar with the vocabulary of immunotherapy and with the evaluation of immune checkpoint and related treatments through noninvasive molecular imaging. Currently, immune target-associated imaging mainly includes PET, SPECT, optical imaging, and MRI...
November 30, 2018: European Radiology
Frédérique Penault-Llorca, Nina Radosevic-Robin
In non-small cell lung cancer (NSCLC), the pathologist has contributed to the development of personalized medicine from the determination of the right histological type to EGFR and ALK/ROS1 molecular screening for targeted therapies. With the development of immunotherapies, pathologists intervene forefront with programmed death-ligand 1 (PD-L1) immunohistochemical testing, companion test for pembrolizumab monotherapy, first line and complementary test to the other programmed cell death-1 (PD-1) PD-L1 inhibitors...
December 2018: Translational Lung Cancer Research
Matthew Evans, Brendan O'Sullivan, Matthew Smith, Philippe Taniere
The selection of patients for immunotherapy remains challenging given the lack of highly specific and highly sensitive biomarkers. Nevertheless, it is essential that testing laboratories are able to fulfil licencing criteria by providing the tests which have been validated as providing useful predictive information. Programmed cell death protein 1 (PD-1) expression assessment is now established in routine practice, although the situation regarding the selection of a particular assay remains complex, and testing protocols are likely to change in future...
December 2018: Translational Lung Cancer Research
Lizza E Hendriks, Etienne Rouleau, Benjamin Besse
Anti-programmed death (ligand)-1 [anti-PD-(L)1] therapies such as pembrolizumab, nivolumab or atezolizumab have become standard of care for non-small cell lung cancer (NSCLC) patients either in first line or beyond. PD-L1 expression level allows enriching the treated population with responders, but it is still not an optimal biomarker. Even in patients with PD-L1 tumor proportion score (TPS) levels of ≥50% treated with first line pembrolizumab overall response rate (ORR) is only 44.8% and overall survival at one year is 70%...
December 2018: Translational Lung Cancer Research
Laurent Greillier, Pascale Tomasini, Fabrice Barlesi
Despite advances made during the last two decades, lung cancer remains the leading cause of cancer-related death worldwide. Recently, immune checkpoint inhibitors (ICIs) became available for the treatment of advanced non-small cell lung cancer (NSCLC) patients. Although ICIs showed a survival advantage in comparison with chemotherapy in the second and first-line setting, overall response rate is only around 20% and a large proportion of patients will undergo disease progression within the first weeks of treatment...
December 2018: Translational Lung Cancer Research
Simon Heeke, Paul Hofman
The emergence of immunotherapy as a first- or second-line of treatment has revolutionized the therapeutic management of lung cancer patients. However, not all lung cancer patients receive the same benefit from this treatment, leading to limitations in the number of patients who can receive anti-PD-1/PD-L1 checkpoint inhibitors because some secondary toxicity has been associated with immunotherapy, and because some patients would benefit more from chemotherapy. In this context, the selection of patients is currently based on PD-L1 immunohistochemistry (IHC), specifically on the percentage of PD-L1 positive tumor cells...
December 2018: Translational Lung Cancer Research
Naohiro Uchida, Kohei Fujita, Misato Okamura, Koichi Nakatani, Tadashi Mio
Thymic carcinomas is rare and highly aggressive carcinoma. Most patients with them are diagnosed as being at surgically unresectable stages due to it. There are several reports which showed the effect of chemotherapy, however, it is controversial. Recently, immune checkpoint inhibitors have changed conventional chemotherapy due to their effect against various types of cancers. We administered nivolumab, anti-Programmed Cell Death (PD)-1 antibody, to four patients with unresectable thymic carcinomas who had previously undergone conventional chemotherapy...
2019: Respiratory Medicine Case Reports
Tomas Jelinek, Bruno Paiva, Roman Hajek
The treatment of cancer, especially of various types of solid tumors, has been revolutionized by the blockade of the PD-1/PD-L1 pathway by immune checkpoint inhibitors. Their success amongst hematologic malignancies, however, has been limited so far to the treatment of classic Hodgkin's lymphoma, which portrays a typical overexpression of PD-1 ligands (PD-L1, PD-L2) as a consequence of changes in chromosome 9p24.1. Their current application in multiple myeloma (MM) is rather uncertain, as discordant results have been reported by distinct research groups concerning especially the expression of PD-1/PD-L1 molecules on malignant plasma cells or on the responsible immune effector cell populations, respectively...
2018: Frontiers in Immunology
Daichi Fujimoto, Daisuke Yamashita, Junya Fukuoka, Yuka Kitamura, Kazutaka Hosoya, Hayato Kawachi, Yuki Sato, Kazuma Nagata, Atsushi Nakagawa, Ryo Tachikawa, Naoki Date, Ichiro Sakanoue, Hiroshi Hamakawa, Yutaka Takahashi, Keisuke Tomii
BACKGROUND/AIM: While the PD-L1 22C3 pharmDx assay is an FDA-approved diagnostic assay for pembrolizumab use, not every pathology laboratory has the Dako Autostainer to use this assay. Since Ventana BenchMark platforms are more common, the Ventana SP263 assay can be used to inform treatment decisions involving nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC). However, some studies have shown discordant results between the two assays. This study aimed was to compare PD-L1 expression using these two assays...
December 2018: Anticancer Research
Xiao-Yun Jia, Qing-Qing Zhu, Yuan-Yuan Wang, Yang Lu, Zhi-Jun Li, Bai-Qing Li, Jie Tang, Hong-Tao Wang, Chuan-Wang Song, Chang-Hao Xie, Lin-Jie Chen
BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19+ B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail. OBJECTIVE: The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE...
November 28, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
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