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pd-l1 and cancer

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https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#1
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28633409/the-effect-of-pd-l1-testing-on-the-cost-effectiveness-and-economic-impact-of-immune-checkpoint-inhibitors-for-the-second-line-treatment-of-nsclc
#2
P N Aguiar, L Perry, J Penny-Dimr, H Babiker, H Tadokoro, R A de Mello, G L Lopes
Background: Immune checkpoint inhibitors improve outcomes compared to chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. Design: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28629895/tumour-suppressor-micrornas-contribute-to-the-regulation-of-pd-l1-expression-in-malignant-pleural-mesothelioma
#3
Steven C Kao, Yuen Yee Cheng, Marissa Williams, Michaela B Kirschner, Jason Madore, Trina Lum, Kadir H Sarun, Anthony Linton, Brian McCaughan, Sonja Klebe, Nico van Zandwijk, Richard A Scolyer, Michael J Boyer, Wendy A Cooper, Glen Reid
INTRODUCTION: The upregulation of PD-L1 is found in many cancers and contributes to the evasion of the host's immune defence. In malignant pleural mesothelioma (MPM), PD-L1 expression is associated with non-epithelioid histological subtype and poor prognosis, but the pathways involved in the control of PD-L1 expression in MPM are poorly understood. To address one possible means of PD-L1 regulation we investigated the relationship between dysregulated microRNA levels and PD-L1 expression...
June 16, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28627635/concomitant-mycobacterium-tuberculosis-infection-promotes-lung-tumor-growth-through-enhancing-treg-development
#4
Yan Zhou, Zhangguo Hu, Shuhui Cao, Bo Yan, Jialin Qian, Hua Zhong
Lung cancer is the most common malignancy in humans. An increased population of CD4+Foxp3+ regulatory T cells (Tregs) in the tumor-associated microenvironment plays an important role in cancer immune evasion. The exact role and the involved mechanisms of concomitant H37Rv infection in non-small cell lung cancer (NSCLC) development are still not clear. Here, we showed that H37Rv infection promoted NSCLC cell growth with a higher percentage of Tregs found in draining lymph nodes. We also determined in vitro that H37Rv infection induced macrophage maturation and PD-L1 expression, which promoted Treg proportion, with enhanced proliferation suppression function...
June 19, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28626408/pd-1-checkpoint-inhibitor-associated-autoimmune-encephalitis
#5
Stephanie Schneider, Silke Potthast, Paul Komminoth, Guido Schwegler, Steffen Böhm
OBJECTIVE: To report first-hand narrative experience of autoimmune encephalitis and to briefly review currently available evidence of autoimmune encephalitis in cancer patients treated with immune checkpoint inhibitors. SETTING: A case study is presented on the management of a patient who developed autoimmune encephalitis during nivolumab monotherapy occurring after 28 weeks on anti-PD-1 monotherapy (nivolumab 3 mg/kg every 2 weeks) for non-small cell lung cancer...
May 2017: Case Reports in Oncology
https://www.readbyqxmd.com/read/28625622/pd-l1-expression-in-neuroendocrine-tumors-of-the-lung
#6
Kenjiro Tsuruoka, Hidehito Horinouchi, Yasushi Goto, Shintaro Kanda, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Keisuke Asakura, Kazuo Nakagawa, Hiroyuki Sakurai, Shun-Ichi Watanabe, Koji Tsuta, Yuichiro Ohe
BACKGROUND: Various tumors express programmed cell death ligand 1 (PD-L1), an immune checkpoint ligand, the expression of which correlates with certain effects of anti-programmed cell death 1 (PD-1)/PD-L1 drugs. The aim of this study was to assess the frequency of PD-L1 expression in each of the types of neuroendocrine tumors of the lung. METHODS: The subjects enrolled in this study were patients who had been diagnosed with neuroendocrine tumors of the lung and had been treated at the National Cancer Center Hospital (Tokyo, Japan) between 1982 and 2010...
June 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28624922/targeting-the-pd-1-pd-l1-immune-checkpoint-in-egfr-mutated-or-alk-translocated-non-small-cell-lung-cancer
#7
Olivier Bylicki, Nicolas Paleiron, Jacques Margery, Florian Guisier, Alain Vergnenegre, Gilles Robinet, Jean-Bernard Auliac, Radj Gervais, Christos Chouaid
Immune checkpoint inhibitors, notably antibodies targeting programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have modified the management of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Several PD-1/PD-L1 inhibitors have been approved by health authorities for this indication and others are in clinical development. However, only a subset of patients truly benefits from these agents. For patients with mutated EGFR or translocated ALK NSCLC, for whom an immune checkpoint inhibitor can be prescribed after progression on tyrosine kinase inhibitors and chemotherapy, information is scarce and sometimes contradictory...
June 18, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28624814/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#8
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624803/prognostic-significance-of-pd-l1-expression-and-18f-fdg-pet-ct-in-surgical-pulmonary-squamous-cell-carcinoma
#9
Minghui Zhang, Dalong Wang, Qi Sun, Haihong Pu, Yan Wang, Shu Zhao, Yan Wang, Qiangyuan Zhang
Programmed cell death-ligand 1 (PD-L1) expression is commonly observed in non-small cell lung cancer (NSCLC). The prognostic value of PD-L1 expression and the maximum standardized uptake value (SUVmax) on 18F-Fluorodeoxyglucose positron emission tomography (18FDG-PET) in surgical pulmonary squamous cell carcinoma(SCC)remains unclear. Furthermore, the correlation between the SUVmax and PD-L1 expression has not been assessed. Thus, the purpose of this study was to investigate the correlation between PD-L1 expression and the SUVmax on 18FDG-PET and to examine the prognostic significance of PD-L1 expression and the SUVmax in surgical pulmonary SCC...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28624577/identification-of-an-immune-specific-class-of-hepatocellular-carcinoma-based-on-molecular-features
#10
Daniela Sia, Yang Jiao, Iris Martinez-Quetglas, Olga Kuchuk, Carlos Villacorta-Martin, Manuel Castro de Moura, Juan Putra, Genis Camprecios, Laia Bassaganyas, Nicholas Akers, Bojan Losic, Samuel Waxman, Swan N Thung, Vincenzo Mazzaferro, Manel Esteller, Scott L Friedman, Myron Schwartz, Augusto Villanueva, Josep M Llovet
BACKGROUND AND AIMS: Agents that induce an immune response against tumors by altering T-cell regulation have increased survival times of patients with advanced-stage tumors, such as melanoma or lung cancer. We aimed to characterize molecular features of immune cells that infiltrate hepatocellular carcinomas (HCCs) to determine whether these types of agents might be effective against liver tumors. METHODS: We analyzed HCC samples from 956 patients. We separated gene expression profiles from tumor, stromal, and immune cells using a non-negative matrix factorization algorithm...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28624449/intratumoral-injection-of-ifn-%C3%AE-induces-chemokine-production-in-melanoma-and-augments-the-therapeutic-efficacy-of-anti-pd-l1-mab
#11
Jiro Uehara, Takayuki Ohkuri, Akemi Kosaka, Kei Ishibashi, Yui Hirata, Kenzo Ohara, Toshihiro Nagato, Kensuke Oikawa, Naoko Aoki, Yasuaki Harabuchi, Akemi Ishida-Yamamoto, Hiroya Kobayashi
Despite recent advances in treatment for melanoma patients through using immune checkpoint inhibitors, these monotherapies have limitations and additional treatments have been explored. Type I IFNs have been used to treat melanoma and possess immunomodulatory effects including enhancement of T-cell infiltration. T-cell plays a critical role in immune checkpoint therapies via restoration of effector functions and tumor infiltration by T-cells predicts longer survival in a variety of cancer types. Moreover, tumor-infiltrating T-cells are associated with the expression of chemokines such as CCL5 and CXCR3 ligands in tumor tissues...
June 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28623908/programmed-death-ligand-1-pd-l1-is-expressed-in-a-significant-number-of-the-uterine-cervical-carcinomas
#12
Opal L Reddy, Peter I Shintaku, Neda A Moatamed
BACKGROUND: The programmed death-1/programmed death-ligand-1 (PD-1/PD-L1) immune regulatory axis has emerged as a promising new target for cancer therapeutics, with lasting responses seen in the treatment of metastatic renal and lung carcinomas, as well as melanomas. As tumor surface expression of PD-L1 has been found to correlate with objective responses to anti-PD-L1 immunotherapies, we investigated the expression of PD-L1 in human cervical tumors and provide an adopted scoring system for the systematic evaluation of PD-L1 staining...
June 17, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28623775/cancer-immunotherapy-opportunities-and-challenges-in-the-rapidly-evolving-clinical-landscape
#13
REVIEW
Leisha A Emens, Paolo A Ascierto, Phillip K Darcy, Sandra Demaria, Alexander M M Eggermont, William L Redmond, Barbara Seliger, Francesco M Marincola
Cancer immunotherapy is now established as a powerful way to treat cancer. The recent clinical success of immune checkpoint blockade (antagonists of CTLA-4, PD-1 and PD-L1) highlights both the universal power of treating the immune system across tumour types and the unique features of cancer immunotherapy. Immune-related adverse events, atypical clinical response patterns, durable responses, and clear overall survival benefit distinguish cancer immunotherapy from cytotoxic cancer therapy. Combination immunotherapies that transform non-responders to responders are under rapid development...
June 14, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28623122/a-randomized-phase-ii-study-comparing-nivolumab-with-carboplatin-pemetrexed-for-patients-with-egfr-mutation-positive-nonsquamous-non-small-cell-lung-cancer-who-acquire-resistance-to-tyrosine-kinase-inhibitors-not-due-to-a-secondary-t790m-mutation-rationale
#14
Hidetoshi Hayashi, Yasutaka Chiba, Kazuko Sakai, Tomonobu Fujita, Hiroshige Yoshioka, Daisuke Sakai, Chiyoe Kitagawa, Tateaki Naito, Koji Takeda, Isamu Okamoto, Tetsuya Mitsudomi, Yutaka Kawakami, Kazuto Nishio, Shinichiro Nakamura, Nobuyuki Yamamoto, Kazuhiko Nakagawa
Antibodies to programmed cell death-1 (PD-1), such as nivolumab, have shown promising clinical activity in patients with advanced non-small-cell lung cancer (NSCLC), but their efficacy appears to be less pronounced in patients with such tumors harboring epidermal growth factor receptor gene (EGFR) mutations. Recent findings suggest that patients with EGFR mutation-positive NSCLC who develop resistance to tyrosine kinase inhibitors (TKIs) due to mechanisms other than acquisition of the secondary T790M mutation of EGFR are more likely to benefit from nivolumab treatment, possibly as a result of a higher level of expression of the PD-1 ligand PD-L1, than are patients who are T790M-positive...
May 25, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28622889/turning-the-tide-clinical-utility-of-pd-l1-expression-in-squamous-cell-carcinoma-of-the-head-and-neck
#15
REVIEW
Astrid De Meulenaere, Tijl Vermassen, Sandrine Aspeslagh, Wouter Huvenne, Jo Van Dorpe, Liesbeth Ferdinande, Sylvie Rottey
The use of cytotoxic and/or targeted agents is the gold standard in first- and second-line treatment of metastatic head and neck cancer. Currently the focus of oncologic research is shifting to the implementation of immune checkpoint inhibitor regimens. Many trials are being performed evaluating the survival benefit of various PD-1/PD-L1 blocking antibodies in both solid and haematological malignancies. Also, evaluation of the predictive value of PD-L1 expression on tumour cells and immune cells is being explored...
July 2017: Oral Oncology
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#16
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622036/molecular-targeted-drugs-and-treatment-of-colorectal-cancer-recent-progress-and-future-perspectives
#17
Fang Geng, Zheng Wang, Hang Yin, Junxian Yu, Bangwei Cao
Nowadays, colorectal cancer is the fourth most common type of tumor all over the world. When diagnosed, ∼50%-60% of tumors have metastasized, thus resulting in a grim prognosis. Chemotherapy is regarded as standard treatment for patients with colorectal cancer, however, limitations of chemotherapy cannot be ignored, such as low selectivity, insufficient concentrations in tumor tissues, and systemic toxicity. Recently, six targeted drugs have been approved by the U.S. Food and Drug Administration (FDA) for treatment of metastatic colorectal cancer (mCRC), including bevacizumab, aflibercept, regorafenib, cetuximab, and panitumumab...
June 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28621686/pseudoprogression-in-microsatellite-instability-high-colorectal-cancer-during-treatment-with-combination-t-cell-mediated-immunotherapy-a-case-report-and-literature-review
#18
Young Kwang Chae, Si Wang, Halla Nimeiri, Aparna Kalyan, Francis J Giles
Evading tumor-mediated immunosuppression through antibodies to immune checkpoints has shown clinical benefit in patients with select solid tumors. There is a heterogeneity of responses in patients receiving immunotherapy, including pseudoprogression in which the tumor burden increases initially before decreasing to reach disease control. The characteristics and basis of pseudoprogression, however, remains poorly understood. We hereby report a case of microsatellite instability (MSI)-high metastatic colorectal cancer treated with combination of OX40 agonist and programmed death ligand-1 (PD-L1) antagonist that demonstrated pseudoprogression reaching 163% increase from baseline tumor burden...
June 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28620848/cost-effectiveness-of-pembrolizumab-vs-standard-of-care-chemotherapy-as-first-line-treatment-for-metastatic-nsclc-that-expresses-high-levels-of-pd-l1-in-the-united-states
#19
Min Huang, Yanyan Lou, James Pellissier, Thomas Burke, Frank Xiaoqing Liu, Ruifeng Xu, Vamsidhar Velcheti
OBJECTIVES: Our objectives were to evaluate the cost effectiveness of pembrolizumab compared with standard-of-care (SoC) platinum-based chemotherapy as first-line treatment in patients with metastatic non-small-cell lung cancer (NSCLC) that expresses high levels of programmed death ligand-1 (PD-L1) [tumour proportion score (TPS) ≥50%], from a US third-party public healthcare payer perspective. METHODS: We conducted a partitioned-survival model with a cycle length of 1 week and a base-case time horizon of 20 years...
June 15, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28619999/pd-l2-expression-in-human-tumors-relevance-to-anti-pd-1-therapy-in-cancer
#20
Jennifer H Yearley, Christopher Gibson, Ni Yu, Christina Moon, Erin Murphy, Jonathan Juco, Jared Lunceford, Jonathan Cheng, Laura Q M Chow, Tanguy Y Seiwert, Masahisa Handa, Joanne E Tomassini, Terrill McClanahan
Purpose: Tumor-associated PD-L1 expression is predictive of clinical response to PD-1-directed immunotherapy. However, PD-L1-negative patients may also respond to PD-1 checkpoint blockade, suggesting that other PD-1 ligands may be relevant to the clinical activity of these therapies. The prevalence of PD-L2, the other known ligand of PD-1, and its relationship to response to anti-PD-1 therapy were evaluated.Experimental Design: PD-L2 expression was assessed in archival tumor tissue from seven indications using a novel immunohistochemical assay...
June 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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