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pd-l1 and cancer

Gustavo Dix Junqueira Pinto, Luciano de Souza Viana, Cristovam Scapulatempo Neto, Sérgio Vicente Serrano
Lung cancer is the leading world cause of cancer-related death, in both genders, and smoking is the main etiological factor. The discovery of immune checkpoints corroborates the hypothesis that ligands presented in tumors modulate the mechanisms of carcinogenesis and the immune activity of tumor microenvironment. Among the most studied coregulatory molecules, PD-1 (programmed cell death 1) and its ligand PD-L1 (programmed cell death 1 ligand 1) are noteworthy. The present study aims to enhance the understanding of the tumor microenvironment of lung cancer patients who underwent surgery, by means of analysis of PD-L1 expression in tumor cells and in intratumoral immune cells (IICs)...
2016: Journal of Immunology Research
Zhaohui Jin, Harry H Yoon
Preliminary clinical studies of anti-programmed cell death-1 (anti-PD-1) therapy in gastro-esophageal cancers have suggested promising single-agent activity. In patients who received prior treatment for advanced disease, pembrolizumab has been associated with a response rate of 20% in programmed cell death-1 ligand 1 (PD-L1)-positive tumors, and nivolumab with a response rate of 12% in unselected tumors. Both agents yielded a median duration of response lasting ~6-7 months. PD-L1 expression and microsatellite instability (MSI) have emerged as potential predictive markers for PD-1/PD-L1 blockade...
October 2016: Journal of Gastrointestinal Oncology
Corey J Langer, Shirish M Gadgeel, Hossein Borghaei, Vassiliki A Papadimitrakopoulou, Amita Patnaik, Steven F Powell, Ryan D Gentzler, Renato G Martins, James P Stevenson, Shadia I Jalal, Amit Panwalkar, James Chih-Hsin Yang, Matthew Gubens, Lecia V Sequist, Mark M Awad, Joseph Fiore, Yang Ge, Harry Raftopoulos, Leena Gandhi
BACKGROUND: Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer (NSCLC) setting. The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy. We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC...
October 10, 2016: Lancet Oncology
Jung-Jyh Hung, Shiu-Feng Huang, Ying-Ying Shen, Yu-Chung Wu, Teh-Ying Chou, Wen-Hu Hsu
BACKGROUND: The programmed cell death-ligand 1 (PD-L1) pathway plays an important role in maintaining immune homeostasis. The PD-L1 pathway may also protect tumors from attack by cytotoxic T cells. Blockade of programmed cell death 1 (PD1) or PD-L1 induced durable tumor regression in patients with advanced cancers, including non-small cell lung cancer (NSCLC). However, the prognostic value of PD-L1 expression in patients with lung adenocarcinoma remains controversial. METHODS: A total of 112 patients with resected lung adenocarcinoma were included in the study...
October 12, 2016: Annals of Thoracic Surgery
A K S Salama, S J Moschos
BACKGROUND: Cancers escape immune surveillance via distinct mechanisms that involve central (negative selection within the thymus) or peripheral (lack of costimulation, receipt of death/anergic signals by tumor, immunoregulatory cell populations) immune tolerance. During the 1990s, moderate clinical benefit was seen using several cytokine therapies for a limited number of cancers. Over the past 20 years, extensive research has been performed to understand the role of various components of peripheral immune tolerance, with the co-inhibitory immune checkpoint molecules cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1), and its ligand (PD-L1) being the most well characterized at preclinical and clinical levels...
October 13, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Hyeyoon Chang, Woon Yong Jung, Youngran Kang, Hyunjoo Lee, Aeree Kim, Han Kyeom Kim, Bong Kyung Shin, Baek-Hui Kim
Gastric adenocarcinoma is one of the most common causes of cancer-related death. In this study, we conducted immunohistochemical studies for PD-L1, PD-1, CTLA-4, and CD8 using tissue microarrays from 464 gastric cancer samples and evaluated the correlations between their expression, clinicopathologic factors, and five-year overall survival. PD-L1 and PD-1 expression was significantly correlated with several adverse prognostic pathologic factors, including higher T-stage, diffuse Lauren histologic type, and lymphatic invasion...
October 12, 2016: Oncotarget
Manish K Thakur, Shirish M Gadgeel
Therapy of non-small cell lung cancer (NSCLC) patients has evolved over the past few years with the incorporation of targeted therapy and immune therapy. These changes have increased the importance of prognostic and predictive biomarkers to enable practicing physicians in making the most appropriate treatment decisions for NSCLC patients. A variety of prognostic factors based on clinical and pathologic features determine the overall outcome of the patient and these factors do influence decisions regarding initiation of therapy...
October 2016: Seminars in Respiratory and Critical Care Medicine
Rin Ogiya, Naoki Niikura, Nobue Kumaki, Giampaolo Bianchini, Shigehisa Kitano, Takayuki Iwamoto, Naoki Hayashi, Kozue Yokoyama, Risa Oshitanai, Mayako Terao, Toru Morioka, Banri Tsuda, Takuho Okamura, Yuki Saito, Yasuhiro Suzuki, Yutaka Tokuda
The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable long-term outcome in breast cancer. However, little is known about changes in TILs during metastatic progression. To confirm our hypothesis that malignant tumours escape from the host immune system during metastasis, we evaluated the percentage of TILs in paired samples of primary and metastatic breast tumours. We retrospectively identified 25 patients with human epidermal growth factor receptor-2 (HER2)-positive (n = 14, HER2+) and triple negative (n = 11, TN) early breast cancer diagnosed during 1990-2009 at Tokai University Hospital and who subsequently experienced regional or distant recurrence confirmed by tumour biopsy/resection...
October 11, 2016: Cancer Science
Satoru Konnai, Shiro Murata, Kazuhiko Ohashi
Recently, dysfunction of antigen-specific T cells is well documented as T-cell exhaustion and has been defined by the loss of effector functions during chronic infections and cancer in human. The exhausted T cells are characterized phenotypically by the surface expression of immunoinhibitory receptors, such as programmed death 1 (PD-1), lymphocyte activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3) and cytotoxic T-lymphocyte antigen 4 (CTLA-4). However, there is still a fundamental lack of knowledge about the immunoinhibitory receptors in the fields of veterinary medicine...
October 8, 2016: Journal of Veterinary Medical Science
Sang Byung Bae, Hyun Deuk Cho, Mee-Hye Oh, Ji-Hye Lee, Si-Hyong Jang, Soon Auck Hong, Junhun Cho, Sung Yong Kim, Sun Wook Han, Jong Eun Lee, Han Jo Kim, Hyun Ju Lee
PURPOSE: The interaction of programmed death receptor 1 (PD-1) and its ligand, programmed death receptor ligand 1 (PD-L1), negatively regulates immune responses. This study aimed to clarify PD-L1 expression levels in breast cancer through immunohistochemistry (IHC) and to evaluate associations between these findings and clinicopathologic variables, including prognosis. METHODS: PD-L1 expression was analyzed using IHC on tissue microarrays of 465 invasive breast carcinomas...
September 2016: Journal of Breast Cancer
Zhifang Chen, Nannan Pang, Rong Du, Yuejie Zhu, Lingling Fan, Donghui Cai, Yan Ding, Jianbing Ding
The present study is to measure the expression of programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), as well as its clinical significance in cervical cancer patients. Our results showed that different T cell subsets in patients with cervical cancer had high expression of PD-1, and DCs had high expression of PD-L1. High expression of PD-1 on Treg cells in cervical cancer patients facilitated the production of TGF-β and IL-10 but inhibited the production of IFN-γ. Cervical cancer elevated the expression of PD-1 and PD-L1 in mRNA level...
2016: Mediators of Inflammation
Kentaro Inamura, Yusuke Yokouchi, Maki Kobayashi, Rie Sakakibara, Hironori Ninomiya, Sophia Subat, Hiroko Nagano, Kimie Nomura, Sakae Okumura, Tomoko Shibutani, Yuichi Ishikawa
OBJECTIVES: Compared with non-smoking counterparts, smoking-associated lung cancers have a higher mutational load, resulting in the creation of more tumor neoantigens and increased immunogenicity. B7-H3 (also known as CD276) belongs to a family of immune modulators that includes PD-1 and PD-L1 (also known as B7-H1 or CD274). Considering the evidence that PD-L1 inhibitors have been shown to be more effective against lung cancer in smokers, we herein examined the prognostic interaction of tumor B7-H3 expression level with smoking history in lung adenocarcinoma patients...
October 1, 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Xi Chen, Jin Xu, Qingcheng Guo, Lingfei Wang, Yun Yang, Huaizu Guo, Nana Gu, Dapeng Zhang, Weizhu Qian, Sheng Hou, Jing Li, Jianxin Dai, Yajun Guo, Hao Wang
Immunocytokines (antibody-cytokine fusions) have been proved to be a promising class of therapeutic agents for tumors. Anti-PD-L1 antibodies or IL-2 have been used to treat a variety of cancers. Here, in order to remove T cell inhibition and increasing the IL-2 concentration in the tumor microenvironment, we engineered a novel anti-PD-L1 antibody based immunocytokine by fusing hIL-2 to the C-Term of atezolizumab, denoted as BIPI. Our results revealed that BIPI was effective in stimulating T cell activation in vitro and could selectively localize to the tumor...
October 5, 2016: Biochemical and Biophysical Research Communications
Congqi Dai, Ruixuan Geng, Chenchen Wang, Angela Wong, Min Qing, Jianjun Hu, Yu Sun, A W I Lo, Jin Li
Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation...
September 24, 2016: Molecular Oncology
Martin Reck, Delvys Rodríguez-Abreu, Andrew G Robinson, Rina Hui, Tibor Csőszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A Leiby, Gregory M Lubiniecki, Yue Shentu, Reshma Rangwala, Julie R Brahmer
Background Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1). Methods In this open-label, phase 3 trial, we randomly assigned 305 patients who had previously untreated advanced NSCLC with PD-L1 expression on at least 50% of tumor cells and no sensitizing mutation of the epidermal growth factor receptor gene or translocation of the anaplastic lymphoma kinase gene to receive either pembrolizumab (at a fixed dose of 200 mg every 3 weeks) or the investigator's choice of platinum-based chemotherapy...
October 8, 2016: New England Journal of Medicine
Marlon C Rebelatto, Anita Midha, Amita Mistry, Constantine Sabalos, Nicole Schechter, Xia Li, Xiaoping Jin, Keith E Steele, Paul B Robbins, John A Blake-Haskins, Jill Walker
BACKGROUND: A high-quality programmed cell-death ligand 1 (PD-L1) diagnostic assay may help predict which patients are more likely to respond to anti-programmed cell death-1 (PD-1)/PD-L1 antibody-based cancer therapy. Here we describe a PD-L1 immunohistochemical (IHC) staining protocol developed by Ventana Medical Systems Inc. and key analytical parameters of its use in formalin-fixed, paraffin-embedded (FFPE) samples of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC)...
October 8, 2016: Diagnostic Pathology
Jiaxing Huang, Yaxiong Zhang, Jin Sheng, Hongyu Zhang, Wenfeng Fang, Jianhua Zhan, Ting Zhou, Ying Chen, Lin Liu, Li Zhang
BACKGROUND: Nivolumab (BMS-936558/ONO-4538) was the first monoclonal antibody targeting programmed death (PD)-1. So far, a number of clinical trials on nivolumab have showed satisfactory efficacy in treating non-small-cell lung cancer (NSCLC). Herein, we present a meta-analysis evaluating the efficacy and safety of nivolumab for previously treated advanced NSCLC patients. METHODS: Electronic databases were searched for eligible literature. Data of objective response rate (ORR), disease control rate, overall survival, progression-free survival, and adverse effects (AEs) were extracted and pooled...
2016: OncoTargets and Therapy
Pankit Vachhani, Hongbin Chen
Immunotherapy with immune checkpoint inhibitors has opened a new arena in cancer therapeutics. Pembrolizumab is a highly selective anti-programmed cell death protein 1 (PD-1) antibody that has shown efficacy, leading to survival benefit and durable responses, in some patients with non-small cell lung cancer (NSCLC). It has been approved by the US Food and Drug Administration for the treatment of patients with metastatic NSCLC, whose tumors express PD-1 ligand 1 (PD-L1), with disease progression on or after platinum-containing chemotherapy...
2016: OncoTargets and Therapy
Eileen E Parkes, Steven M Walker, Laura E Taggart, Nuala McCabe, Laura A Knight, Richard Wilkinson, Karen D McCloskey, Niamh E Buckley, Kienan I Savage, Manuel Salto-Tellez, Stephen McQuaid, Mary T Harte, Paul B Mullan, D Paul Harkin, Richard D Kennedy
BACKGROUND: Previously we identified a DNA damage response-deficient (DDRD) molecular subtype within breast cancer. A 44-gene assay identifying this subtype was validated as predicting benefit from DNA-damaging chemotherapy. This subtype was defined by interferon signaling. In this study, we address the mechanism of this immune response and its possible clinical significance. METHODS: We used immunohistochemistry (IHC) to characterize immune infiltration in 184 breast cancer samples, of which 65 were within the DDRD subtype...
January 2017: Journal of the National Cancer Institute
C Baues, R Semrau, U S Gaipl, P J Bröckelmann, J Rosenbrock, A Engert, S Marnitz
BACKGROUND: Patients with classical Hodgkin's lymphoma (cHL) have a good prognosis even in advanced stages. However, combined chemo- and radiotherapy, as the standard of care, is also associated with treatment-related toxicities such as organ damage, secondary neoplasias, infertility, or fatigue and long-term fatigue. Many patients suffer from this burden although their cHL was cured. Therefore, the efficacy of immune checkpoint inhibitors like anti-PD1/PD-L1 antibodies in the treatment of solid cancers and also in HL offers new options...
October 4, 2016: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
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