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Program death ligand 1/2

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https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#1
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723616/prognostic-value-of-programmed-death-ligand-1-in-sarcoma-a-meta-analysis
#2
Zhenhua Zhu, Zheng Jin, Mei Zhang, Yajun Tang, Guang Yang, Xiaowei Yuan, Jihang Yao, Dahui Sun
BACKGROUND: The prognostic role of programmed death-ligand 1 (PD-L1) in sarcoma remains controversial. We performed a meta-analysis so as to investigate the impact of PD-L1 on clinicopathlogical findings and survival outcomes in sarcoma. MATERIALS AND METHODS: A comprehensive search in PubMed, Embase and the Cochrane Library was conducted for relevant studies. The odds ratios or hazard ratios, at 95% confidence intervals were used as measures for investigation of the correlation between PD-L1 expression and clinicopathlogical features or survival outcomes...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723489/immunotherapy-for-renal-cancer-sequencing-and-combinations
#3
REVIEW
Grant D Stewart, Maria De Santis, Bernard Escudier, Thomas Powles, Guru Sonpavde
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28719380/comparison-of-different-antibody-clones-for-immunohistochemistry-detection-of-programmed-cell-death-ligand-1-pd-l1-on-non-small-cell-lung-carcinoma
#4
Edwin R Parra, Pamela Villalobos, Barbara Mino, Jaime Rodriguez-Canales
Programmed cell death ligand 1 (PD-L1) is a major immune checkpoint protein that mediates antitumor immune suppression and response. Preliminary data suggest that its detection using immunohistochemistry (IHC) in formalin-fixed and paraffin-embedded tissues may predict clinical response to PD-1/PD-L1 therapy. In diagnostic pathology, it is essential to count with a validated IHC that can reliably detect PD-L1-positive cases. The present study was conducted to compare and validate different PD-L1 commercial clones and identify which ones can be reliably used by surgical pathologist to detect PD-L1 expression in human cancer tissues...
July 17, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28716437/tumor-programmed-cell-death-ligand-1-expression-correlates-with-nodal-metastasis-in-patients-with-cutaneous-squamous-cell-carcinoma-of-the-head-and-neck
#5
Juana María García-Pedrero, Pablo Martínez-Camblor, Susana Diaz-Coto, Pablo Munguia-Calzada, Aitana Vallina-Alvarez, Francisco Vazquez-Lopez, Juan Pablo Rodrigo, Jorge Santos-Juanes
BACKGROUND: Binding of tumor-expressed programmed cell death ligand 1 (PD-L1) to the programmed cell death 1 (PD-1) surface receptor blocks T-cell activation thereby leading to immune evasion. Tumor PD-L1 expression has been associated with poor outcome in a wide variety of cancers; however, data in cutaneous squamous cell carcinoma (cSCC) are scarce and conflicting. OBJECTIVE: To investigate the relationship of tumor PD-L1 expression with the clinicopathologic features and prognosis of cSCC...
July 14, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/28697172/immunogenic-chemotherapy-sensitizes-renal-cancer-to-immune-checkpoint-blockade-therapy-in-preclinical-models
#6
Shujin Cui
BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo...
July 11, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28697066/viral-induced-modulation-of-multiple-checkpoint-proteins-in-cancers
#7
Gerard J Nuovo, Virginia A Folcik, Cynthia Magro
Therapy with checkpoint inhibitors represents a major advance in cancer treatment. The purpose of this study was to examine the expression patterns of the checkpoint proteins programmed death ligand 1 (PD L1), PD L2, indoleamine 2,3-dioxygenase 1 (IDO1), and cytotoxic T-lymphocyte antigen 4 (CTLA4) in cancers including those associated with viral infections. Normal, noninflamed tissues rarely express checkpoint proteins with exceptions including the placenta and stomach. Expression of PD L1 was noted in 30%, PD L2 in 18%, IDO1 in 13%, and CTLA4 in 14% of 333 nonviral malignancies including endometrial, ovarian, lung, and breast cancers...
July 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28693256/pirfenidone-may-revert-the-epithelial-to-mesenchymal-transition-in-human-lung-adenocarcinoma
#8
Ryota Kurimoto, Takahiro Ebata, Shunichiro Iwasawa, Tsukasa Ishiwata, Yuji Tada, Koichiro Tatsumi, Yuichi Takiguchi
The epithelial-to-mesenchymal transition (EMT) in cancer is associated with invasion, metastasis and chemoresistance. Recent studies have revealed the increased expression of programmed death-ligand 1 (PD-L1) in cells undergoing EMT. The underlying mechanism of EMT involves transforming growth factor-β (TGF-β) and fibroblast growth factor-2 (FGF-2). Pirfenidone and the known EMT-suppressor nintedanib suppress pulmonary fibrosis partially through suppression of TGF-β. The present study aimed to determine whether pirfenidone has the potential to induce EMT-reversion, using nintedanib as a reference...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28689001/immuno-oncologic-approaches-car-t-cells-and-checkpoint-inhibitors
#9
REVIEW
Francesca Gay, Mattia D'Agostino, Luisa Giaccone, Mariella Genuardi, Moreno Festuccia, Mario Boccadoro, Benedetto Bruno
Advances in understanding myeloma biology have shown that disease progression is not only the consequence of intrinsic tumor changes but also of interactions between the tumor and the microenvironment in which the cancer grows. The immune system is an important component of the tumor microenvironment in myeloma, and acting on the immune system is an appealing new treatment strategy. There are 2 ways to act toward immune cells and boost antitumor immunity: (1) to increase antitumor activity (acting on T and NK cytotoxic cells), and (2) to reduce immunosuppression (acting on myeloid-derived stem cells and T regulatory cells)...
June 17, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28681030/novel-immunotherapy-in-metastatic-renal-cell-carcinoma
#10
REVIEW
Yang Hyun Cho, Myung Soo Kim, Ho Seok Chung, Eu Chang Hwang
Despite the rapid development of therapeutic modalities for metastatic renal cell carcinoma (mRCC) over the past decade to include a number of targeted antiangiogenic therapies and traditional immunotherapy, such as high-dose interleukin-2 and interferon-α, mRCC continues to be associated with poor prognosis. Currently, several novel immunotherapy agents, such as cancer vaccines, adoptive cell therapy, and checkpoint inhibitors, such as programmed cell death-1 (PD-1 present on T cells), one of its ligands (PD-L1 present on antigen-presenting cells and tumor cells), and cytotoxic T-lymphocyte-associated protein-4 pathways, are being studied in mRCC and are showing promise as important steps in the management of this disease...
July 2017: Investigative and Clinical Urology
https://www.readbyqxmd.com/read/28673339/human-limbal-fibroblast-like-stem-cells-induce-immune-tolerance-in-autoreactive-t-lymphocytes-from-female-patients-with-hashimoto-s-thyroiditis
#11
Antonina Coppola, Laura Tomasello, Maria Pitrone, Salvatore Cillino, Pierina Richiusa, Giuseppe Pizzolanti, Carla Giordano
BACKGROUND: Due to their "natural immune privilege" and immunoregulatory properties human fibroblast-like limbal stem cells (f-LSCs) have acquired great interest as a potential tool for achieving immunotolerance. Hashimoto's thyroiditis (HT) is the most common thyroid autoimmune disease and cause of hypothyroidism. To date, conventional hormone replacement therapy and unspecific immunosuppressive regimens cannot provide a definitive cure for HT subjects. We explored the immunosuppressant potential of human f-LSCs on circulating lymphomonocytes (PBMCs) collected from healthy donors and female HT patients...
July 3, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28671856/overall-survival-in-patients-with-advanced-melanoma-who-received-nivolumab-versus-investigator-s-choice-chemotherapy-in-checkmate-037-a-randomized-controlled-open-label-phase-iii-trial
#12
James Larkin, David Minor, Sandra D'Angelo, Bart Neyns, Michael Smylie, Wilson H Miller, Ralf Gutzmer, Gerald Linette, Bartosz Chmielowski, Christopher D Lao, Paul Lorigan, Kenneth Grossmann, Jessica C Hassel, Mario Sznol, Adil Daud, Jeffrey Sosman, Nikhil Khushalani, Dirk Schadendorf, Christoph Hoeller, Dana Walker, George Kong, Christine Horak, Jeffrey Weber
Purpose Until recently, limited options existed for patients with advanced melanoma who experienced disease progression while receiving treatment with ipilimumab. Here, we report the coprimary overall survival (OS) end point of CheckMate 037, which has previously shown that nivolumab resulted in more patients achieving an objective response compared with chemotherapy regimens in ipilimumab-refractory patients with advanced melanoma. Patients and Methods Patients were stratified by programmed death-ligand 1 expression, BRAF status, and best prior cytotoxic T-lymphocyte antigen-4 therapy response, then randomly assigned 2:1 to nivolumab 3 mg/kg intravenously every 2 weeks or investigator's choice chemotherapy (ICC; dacarbazine 1,000 mg/m(2) every 3 weeks or carboplatin area under the curve 6 plus paclitaxel 175 mg/m(2) every 3 weeks)...
July 3, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28670887/programmed-death-ligand-1-pd-l1-expression-associated-with-a-high-neutrophil-lymphocyte-ratio-in-cholangiocarcinoma
#13
Sakkarn Sangkhamanon, Piangpen Jongpairat, Aumkhae Sookprasert, Kosin Wirasorn, Attapol Titapun, Ake Pugkhem, Piti Ungareevittaya, Jarin Chindaprasirt
Background: Effective treatments for cholangiocarcinoma (CCA) are still lacking. There are promising results of checkpoint inhibitor programmed cell death ligand-1 (PD-L1) activities in early phase trials. This study aimed to investigate the expression of PD-L1 and its relation to possible treatments for CCA. Methods: Formalin-fixed paraffin-embedded tumor samples from 46 patients with cholangiocarcinoma were retrieved. PD-L1 expression was evaluated by immunohistochemistry using anti-PD-L1 antibody, clone 5H1...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28669849/programmed-death-ligand-1-expression-in-paired-non-small-cell-lung-cancer-tumor-samples
#14
Jong Ho Cho, Steffen Filskov Sorensen, Yoon-La Choi, Yu Feng, Tae-Eun Kim, Heyjoo Choi, Jeanette Baehr Georgsen, Marisa Dolled-Filhart, Kenneth Emancipator, Peter Meldgaard, Jong-Mu Sun, Hong Kwan Kim, Yong Soo Choi, Young Mog Shim, Wei Zhou, Henrik Hager, Jhingook Kim
BACKGROUND: Programmed death ligand 1 (PD-L1) expression may predict response to anti-programmed death 1 (anti-PD-1) or anti-PD-L1 treatment. There is limited information on changes in PD-L1 expression over time in patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Eligible patients with NSCLC who received surgery or underwent biopsy at Samsung Medical Center, Seoul, Republic of Korea, and Aarhus University Hospital, Aarhus, Denmark, between February 2004 and April 2012 were included...
April 24, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28666240/myasthenia-gravis-an-emerging-toxicity-of-immune-checkpoint-inhibitors
#15
REVIEW
D Makarious, K Horwood, J I G Coward
The advent of immunotherapy has heralded a number of significant advances in the treatment of particular malignancies associated with poor prognosis (melanoma, non-small-cell lung, renal and head/neck cancers). The success witnessed with therapeutic agents targeting cytotoxic T-lymphocyte-associated protein 4, programmed cell death protein 1 and programmed cell death ligand 1 immune checkpoints has inevitably led to an explosion in their clinical application and the subsequent recognition of specific toxicity profiles distinct from those long recognised with chemotherapy...
June 27, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28664936/pd-l1-immunohistochemistry-in-clinical-diagnostics-of-lung-cancer-inter-pathologist-variability-is-higher-than-assay-variability
#16
Hans Brunnström, Anna Johansson, Sofia Westbom-Fremer, Max Backman, Dijana Djureinovic, Annika Patthey, Martin Isaksson-Mettävainio, Miklos Gulyas, Patrick Micke
Assessment of programmed cell death ligand 1 (PD-L1) immunohistochemical staining is used for decision on treatment with programmed cell death 1 and PD-L1 checkpoint inhibitors in lung adenocarcinomas and squamous cell carcinomas. This study aimed to compare the staining properties of tumor cells between the antibody clones 28-8, 22C3, SP142, and SP263 and investigate interrater variation between pathologists to see if these stainings can be safely evaluated in the clinical setting. Using consecutive sections from a tissue microarray with tumor tissue from 55 resected lung cancer cases, staining with five PD-L1 assays (28-8 from two different vendors, 22C3, SP142, and SP263) was performed...
June 30, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28662235/use-of-pd-1-targeting-macrophage-infiltration-and-ido-pathway-activation-in-sarcomas-a-phase-2-clinical-trial
#17
Maud Toulmonde, Nicolas Penel, Julien Adam, Christine Chevreau, Jean-Yves Blay, Axel Le Cesne, Emmanuelle Bompas, Sophie Piperno-Neumann, Sophie Cousin, Thomas Grellety, Thomas Ryckewaert, Alban Bessede, François Ghiringhelli, Marina Pulido, Antoine Italiano
Importance: There is a strong rationale for treating sarcomas with immunotherapy. Objective: To assess the efficacy and safety of programmed cell death protein 1 (PD-1) targeting in combination with metronomic chemotherapy in sarcomas. Design, Setting, and Participants: This was an open-label, multicenter, phase 2 study of 4 cohorts of patients with advanced soft-tissue sarcoma (STS), including leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), other sarcomas (others), and gastrointestinal stromal tumor (GIST)...
June 29, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28659503/nonsmall-cell-lung-carcinoma-diagnostic-difficulties-in-small-biopsies-and-cytological-specimens-number-2-in-the-series-pathology-for-the-clinician-edited-by-peter-dorfm%C3%A3-ller-and-alberto-cavazza
#18
Lukas Bubendorf, Sylvie Lantuejoul, Adrianus J de Langen, Erik Thunnissen
The pathological and molecular classification of lung cancer has become substantially more complex over the past decade. For diagnostic purposes on small samples, additional stains are frequently required to distinguish between squamous cell carcinoma and adenocarcinoma. Subsequently, for advanced nonsquamous cell nonsmall cell lung carcinoma (NSCLC) patients, predictive analyses on epidermal growth factor receptor, anaplastic lymphoma kinase and ROS1 are required. In NSCLCs negative for these biomarkers, programmed death ligand-1 immunohistochemistry is performed...
June 30, 2017: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/28658669/shp2-negatively-regulates-hla-abc-and-pd-l1-expression-via-stat1-phosphorylation-in-prostate-cancer-cells
#19
Zhuqing Liu, Yu Zhao, Juemin Fang, Ran Cui, Yuanyuan Xiao, Qing Xu
Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) is a ubiquitous protein tyrosine phosphatase that activates the signal transduction pathways of several growth factors and cytokines. In our study, SHP2 expression was very high in prostate cancer (PCa) cell lines, and the expression of phospho-signal transducer and activator of transcription 1 (p-STAT1) and STAT1 was very low. SHP2 knockdown upregulated the expression of p-STAT1 and downregulated phospho-extracellular signal regulated kinase (p-ERK)...
June 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28652622/the-prognostic-significance-of-pd-l1-expression-in-patients-with-glioma-a-meta-analysis
#20
Song Xue, Ge Song, Jinming Yu
A large number of studies have shown that programmed death-ligand 1 (PD-L1) is abnormally expressed in gliomas. However, the prognostic significance of PD-L1 expression in glioma patients remains unresolved. Accordingly, we conducted a meta-analysis to determine the prognostic role of high PD-L1 in patients with glioma. Electronic databases were searched to identify studies evaluating PD-L1 expression and overall survival (OS) in these patients. A total of 6 studies (published in 4 articles) that involved 1052 patients were included...
June 26, 2017: Scientific Reports
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