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pd-l1 and cancer

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https://www.readbyqxmd.com/read/29775808/phase-ii-study-of-maintenance-pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-sclc
#1
Shirish M Gadgeel, Nathan A Pennell, Mary Jo Fidler, Balazs Halmos, Philip Bonomi, James Stevenson, Bryan Schneider, Ammar Sukari, Jaclyn Ventimiglia, Wei Chen, Cathy Galasso, Antoinette Wozniak, Julie Boerner, Gregory P Kalemkerian
PURPOSE: To assess the efficacy of maintenance pembrolizumab in extensive-stage small cell lung cancer (SCLC) patients, after treatment with platinum/etoposide. PATIENTS AND METHODS: Extensive-stage SCLC patients with a response or stable disease following induction chemotherapy were eligible. Pembrolizumab at a dose of 200 mg IV every 3 weeks was initiated within 8 weeks of the last cycle of chemotherapy. The primary endpoint of the study was progression-free survival (PFS) from study registration, with overall survival (OS) as a key secondary endpoint...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29775807/fir-efficacy-safety-and-biomarker-analysis-of-a-phase-ii-open-label-study-of-atezolizumab-in-pd-l1-selected-patients-with-non-small-cell-lung-cancer
#2
David R Spigel, Jamie E Chaft, Scott Gettinger, Bo H Chao, Luc Dirix, Peter Schmid, Laura Q M Chow, Rodney J Hicks, Larry Leon, Jill Fredrickson, Marcin Kowanetz, Alan Sandler, Roel Funke, Naiyer A Rizvi
INTRODUCTION: The FIR phase II study (NCT01846416) evaluated the efficacy and safety of anti-programmed death-ligand 1 (PD-L1) atezolizumab in advanced non-small-cell lung cancer (NSCLC) selected by tumor cell (TC) or tumor-infiltrating immune cell (IC) PD-L1 expression. METHODS: Patients with PD-L1 TC2/3 (PD-L1 staining on ≥5% of TC) or IC2/3 tumors (PD-L1 staining on ≥5% of IC; determined by SP142 PD-L1 immunohistochemistry assay) with paired fresh and archival histology samples were recruited into Cohort 1 (chemotherapy-naïve/>6 months between adjuvant chemotherapy and recurrence), Cohort 2 (≥ second-line without brain metastases), or Cohort 3 (≥ second-line with treated brain metastases)...
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29770915/cytolytic-activity-score-to-assess-anticancer-immunity-in-colorectal-cancer
#3
Sumana Narayanan, Tsutomu Kawaguchi, Li Yan, Xuan Peng, Qianya Qi, Kazuaki Takabe
BACKGROUND: Elevated tumor-infiltrating lymphocytes (TILs) within the tumor microenvironment is a known positive prognostic factor in colorectal cancer (CRC). We hypothesized that since cytotoxic T cells release cytolytic proteins such as perforin (PRF1) and pro-apoptotic granzymes (GZMA) to attack cancer cells, a cytolytic activity score (CYT) would be a useful tool to assess anticancer immunity. METHODS: Genomic expression data were obtained from 456 patients from The Cancer Genome Atlas (TCGA)...
May 16, 2018: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/29769207/mitigating-sox2-potentiated-immune-escape-of-head-and-neck-squamous-cell-carcinoma-with-a-sting-inducing-nanosatellite-vaccine
#4
Yee Sun Tan, Kanokwan Sansanaphongpricha, Yuying Xie, Christopher R Donnelly, Xiaobo Luo, Blake R Heath, Xinyi Zhao, Emily L Bellile, Hongxiang Hu, Hongwei Chen, Peter J Polverini, Qianming Chen, Simon Young, Thomas E Carey, Jacques E Nör, Robert L Ferris, Gregory Wolf, Duxin Sun, Yu L Lei
PURPOSE: The response rates of Head and Neck Squamous Cell Carcinoma (HNSCC) to checkpoint blockade are below 20%. We aim to develop a mechanism-based vaccine to prevent HNSCC immune escape. EXPERIMENTAL DESIGN: We performed RNA-Seq of sensitive and resistant HNSCC cells to discover central pathways promoting resistance to immune killing. Using biochemistry, animal models, HNSCC microarray and immune cell deconvolution, we assessed the role of SOX2 in inhibiting STING-type I interferon (IFN-I) signaling-mediated anti-tumor immunity...
May 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#5
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29767245/mir-142-5p-regulates-cd4-t-cells-in-human-non-small-cell-lung-cancer-through-pd-l1-expression-via-the-pten-pathway
#6
Jun Wan, Xiean Ling, Bin Peng, Guanggui Ding
The present study aimed to evaluate the function of microRNA (miR)-142-5p on cancer immunity to induce apoptosis in human non-small cell lung cancer (NSCLC) and its mechanism. miR-142-5p expression was upregulated, and CD4+ T cell levels were reduced in patients with NSCLC. Overexpression of miR-142-5p expression inhibited the cancer effects of CD4+ T cells on NSCLC cell lines, and downregulation of miR-142-5p increased the cancer effects of CD4+ T cells on NSCLC cell lines, compared with the control group...
May 16, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29765155/genetic-transcriptional-and-post-translational-regulation-of-the-programmed-death-protein-ligand-1-in-cancer-biology-and-clinical-correlations
#7
REVIEW
Ioannis Zerdes, Alexios Matikas, Jonas Bergh, George Z Rassidakis, Theodoros Foukakis
The programmed death protein 1 (PD-1) and its ligand (PD-L1) represent a well-characterized immune checkpoint in cancer, effectively targeted by monoclonal antibodies that are approved for routine clinical use. The regulation of PD-L1 expression is complex, varies between different tumor types and occurs at the genetic, transcriptional and post-transcriptional levels. Copy number alterations of PD-L1 locus have been reported with varying frequency in several tumor types. At the transcriptional level, a number of transcriptional factors seem to regulate PD-L1 expression including HIF-1, STAT3, NF-κΒ, and AP-1...
May 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29765039/stt3-dependent-pd-l1-accumulation-on-cancer-stem-cells-promotes-immune-evasion
#8
Jung-Mao Hsu, Weiya Xia, Yi-Hsin Hsu, Li-Chuan Chan, Wen-Hsuan Yu, Jong-Ho Cha, Chun-Te Chen, Hsin-Wei Liao, Chu-Wei Kuo, Kay-Hooi Khoo, Jennifer L Hsu, Chia-Wei Li, Seung-Oe Lim, Shih-Shin Chang, Yi-Chun Chen, Guo-Xin Ren, Mien-Chie Hung
Enriched PD-L1 expression in cancer stem-like cells (CSCs) contributes to CSC immune evasion. However, the mechanisms underlying PD-L1 enrichment in CSCs remain unclear. Here, we demonstrate that epithelial-mesenchymal transition (EMT) enriches PD-L1 in CSCs by the EMT/β-catenin/STT3/PD-L1 signaling axis, in which EMT transcriptionally induces N-glycosyltransferase STT3 through β-catenin, and subsequent STT3-dependent PD-L1 N-glycosylation stabilizes and upregulates PD-L1. The axis is also utilized by the general cancer cell population, but it has much more profound effect on CSCs as EMT induces more STT3 in CSCs than in non-CSCs...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764856/-tp53-stk11-and-egfr-mutations-predict-tumor-immune-profile-and-the-response-to-anti-pd-1-in-lung-adenocarcinoma
#9
Jerome Biton, Audrey Mansuet-Lupo, Nicolas Pécuchet, Marco Alifano, Hanane Ouakrim, Jennifer Arrondeau, Pascaline Boudou-Rouquette, Francois Goldwasser, Karen Leroy, Jeremy Goc, Marie Wislez, Claire Germain, Pierre Laurent-Puig, Marie-Caroline Dieu-Nosjean, Isabelle Cremer, Ronald Herbst, Hélène F Blons, Diane Damotte
PURPOSE: By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. EXPERIMENTAL DESIGN: We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data...
May 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29764752/successful-treatment-by-pembrolizumab-in-a-patient-with-end-stage-renal-disease-with-advanced-non-small-cell-lung-cancer-and-high-pd-l1-expression
#10
Shiho Ishizuka, Shinya Sakata, Chieko Yoshida, Akira Takaki, Sho Saeki, Kazuyoshi Nakamura, Kazuhiko Fujii
We report a 66-year-old Japanese male with end-stage renal disease (ESRD) and advanced non-small cell lung cancer (NSCLC) who was on hemodialysis. The patient harbored high programmed death ligand 1 (PD-L1) expression and was successfully treated with pembrolizumab. Laboratory examination upon diagnosis showed elevated serum creatinine (6.58 mg/dL). We administered pembrolizumab (200 mg/body) and repeated every 3 weeks. His renal dysfunction gradually progressed, hemodialysis was initiated after eight courses of pembrolizumab, and the antitumor effect was maintained at five months after hemodialysis initiation...
May 10, 2018: Respiratory Investigation
https://www.readbyqxmd.com/read/29764164/immunoregulatory-antigens-novel-targets-for-cancer-immunotherapy
#11
Ayako Wakatsuki Pedersen, Katharina L Kopp, Mads Hald Andersen, Mai-Britt Zocca
Historically, the development of cancer vaccines has focused on the central role of tumor antigens in eliciting tumor-specific immune responses, with limited success. Recent advances with checkpoint blockade approaches have brought about a renewed appreciation of the importance of targeting immune suppression in cancer patients. Here we discuss a novel approach to cancer immunotherapy, namely to target recently described T cells that uniquely control cells with immune suppressive functions. Accumulating evidence support the existence of self-reactive T cells that are specific to antigens derived from immunoregulatory proteins ("immunoregulatory antigens"), such as indoleamine 2,3-dioxygenase (IDO) and PD-L1...
April 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29762727/development-of-targeted-therapy-and-immunotherapy-for-treatment-of-small-cell-lung-cancer
#12
Motonobu Saito, Kouya Shiraishi, Akiteru Goto, Hiroyuki Suzuki, Takashi Kohno, Koji Kono
Targeted therapy against druggable genetic aberrations has shown a significantly positive response rate and longer survival in various cancers, including lung cancer. In lung adenocarcinoma (LADC), specific thyroxin kinase inhibitors against EGFR mutations and ALK fusions are used as a standard treatment regimen and show significant positive efficacy. On the other hand, targeted therapy against driver gene aberrations has not been adapted yet in small cell lung cancer (SCLC). This is because driver genes and druggable aberrations are rarely identified by next generation sequencing in SCLC...
May 14, 2018: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29762141/pd-1-expression-in-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-large-b-cell-richter-transformation-dlbcl-rt-a-characteristic-feature-of-dlbcl-rt-and-potential-surrogate-marker-for-clonal-relatedness
#13
Rong He, Wei Ding, David S Viswanatha, Dong Chen, Min Shi, Daniel Van Dyke, Shulan Tian, Linda N Dao, Sameer A Parikh, Tait D Shanafelt, Timothy G Call, Stephen M Ansell, Jose F Leis, Ming Mai, Curtis A Hanson, Karen L Rech
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a low-grade B-cell neoplasm and ∼2% to 9% patients develop an aggressive lymphoma, most commonly diffuse large B-cell lymphoma (Richter transformation, DLBCL-RT). Programmed death-1 (PD-1) pathway plays a crucial role in tumor host immunity evasion and its blockade has emerged as an effective anti-cancer immunotherapy. PD-L1 and PD-1 expression has shown predictive value in anti-PD cancer immunotherapy; however, it has not been well documented in CLL/SLL and DLBCL-RT...
May 14, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29761938/lactoferricin-b-reverses-cisplatin-resistance-in-head-and-neck-squamous-cell-carcinoma-cells-through-targeting-pd-l1
#14
Pei Zhang, Jinzhong Liu, Wenlu Li, Shanshan Li, Xinguang Han
Head and neck squamous cell carcinoma (HNSCC) ranks among the top most common cancers with a poor prognosis. The mechanism of chemoresistance is still not well known. This study is to investigate the programmed death-ligand 1 (PD-L1) expression in HNSCC, and test the effect of lactoferricin B (LfcinB) on chemoresistance and its mechanism. We analyzed 510 HNSCC patients in TCGA database and investigated how CD274 expression was related to patient prognosis. PD-L1 was verified from HNSCC samples at local hospital with immunohistochemistry...
May 15, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29760834/a-case-series-of-two-patients-presenting-with-pericardial-effusion-as-first-manifestation-of-non-small-cell-lung-cancer-with-braf-mutation-and-expression-of-pd-l1
#15
Muhammad Mufti, Steven Ching, Sassan Farjami, Sharareh Shahangian, Serap Sobnosky
Lung cancer is the number one cause of cancer-related deaths in the United States. Involvement of pericardium occurs once cancer has progressed to stage IV which can cause massive effusion in the pericardial sac. This can lead to cardiac tamponade which can be fatal very quickly if untreated. The following is a two patient case series in which both patients presented with large pericardial effusion. The first patient sought medical attention due to new onset palpitations and was found to have hemorrhagic pericardial effusion and pulmonary embolism (PE)...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29760833/synchronous-presence-of-egfr-alk-driver-mutations-along-with-pd-l1-overexpression-in-a-resected-early-stage-non-small-cell-lung-cancer-a-case-report-and-review-of-literature
#16
Nishitha Thumallapally, Sara Parylo, Adarsh Vennepureddy, Uroosa Ibrahim, Alisa Sokoloff
Treatment of lung cancer has been revolutionized with development of drugs that target key driver mutations and immune checkpoints. Until recently, it was believed that these driver mutations are mutually exclusive. However, few reports have emerged citing the presence of both mutations either synchronously or metachronously. We describe a case report of lung adenocarcinoma harboring two driver mutations in the same tumor cells as well as exhibiting high PDL1 expression. We further discuss the possible association of these driver mutations with PDL1 expression...
April 2018: World Journal of Oncology
https://www.readbyqxmd.com/read/29758930/the-potential-predictive-value-of-circulating-immune-cell-ratio-and-tumor-marker-in-atezolizumab-treated-advanced-non-small-cell-lung-cancer-patients
#17
Minglei Zhuo, Hanxiao Chen, Tianzhuo Zhang, Xue Yang, Jia Zhong, Yuyan Wang, Tongtong An, Meina Wu, Ziping Wang, Jing Huang, Jun Zhao
BACKGROUND: The PD-L1 antibody atezolizumab has shown promising efficacy in patients with advanced non-small cell lung cancer. But the predictive marker of clinical benefit has not been identified. OBJECTIVE: This study aimed to search for potential predictive factors in circulating blood of patients receiving atezolizumab. METHODS: Ten patients diagnosed with advanced non-small cell lung cancer were enrolled in this open-label observing study...
May 4, 2018: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29757193/eya3-promotes-breast-tumor-associated-immune-suppression-via-threonine-phosphatase-mediated-pd-l1-upregulation
#18
Rebecca L Vartuli, Hengbo Zhou, Lingdi Zhang, Rani K Powers, Jared Klarquist, Pratyaydipta Rudra, Melanie Y Vincent, Debashis Ghosh, James C Costello, Ross M Kedl, Jill E Slansky, Rui Zhao, Heide L Ford
Eya proteins are critical developmental regulators that are highly expressed in embryogenesis but downregulated after development. Amplification and/or re-expression of Eyas occurs in many tumor types. In breast cancer, Eyas regulate tumor progression by acting as transcriptional cofactors and tyrosine phosphatases. Intriguingly, Eyas harbor a separate threonine (Thr) phosphatase activity, which was previously implicated in innate immunity. Here we describe what we believe to be a novel role for Eya3 in mediating triple-negative breast cancer-associated immune suppression...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29756991/the-immune-landscape-of-non-small-cell-lung-cancer-utility-of-cytologic-and-histologic-samples-obtained-through-minimally-invasive-pulmonary-procedures
#19
Jason Beattie, Lonny Yarmus, Momen Wahidi, M Patricia Rivera, Christopher Gilbert, Fabien Maldonado, Kasia Czarnecka, Angela Argento, Alexander Chen, Felix Herth, Daniel H Sterman
The success of immune checkpoint inhibitors and the discovery of useful biomarkers to predict response to these agents has shifted much of the focus of personalized care for advanced non-small cell lung cancer towards harnessing the immune response. With further advancement, more effective immunotherapy options will emerge along with more useful biomarkers. For patients with advanced disease, minimally invasive techniques will remain most appropriate for acquisition of tissue. This is in contrast to default gold-standard large tissue specimens obtained through surgical resection...
May 14, 2018: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/29756633/immunotherapy-in-head-and-neck-cancer-scientific-rationale-current-treatment-options-and-future-directions
#20
Uta Rothschild, Laurent Muller, Axel Lechner, Hans A Schlösser, Dirk Beutner, Heinz Läubli, Alfred Zippelius, Sacha I Rothschild
Head and neck squamous cell carcinoma (HNSCC) is a frequent tumour arising from multiple anatomical subsites in the head and neck region. The treatment for early-stage disease is generally single modality, either surgery or radiotherapy. The treatment for locally advanced tumours is multimodal. For recurrent/metastatic HNSCC palliative chemotherapy is standard of care. The prognosis is limited and novel treatment approaches are urgently needed. HNSCC evades immune responses through multiple resistance mechanisms...
May 14, 2018: Swiss Medical Weekly
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