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Pd-l1 Trafficking

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https://www.readbyqxmd.com/read/30173533/next-frontiers-in-systemic-therapy-for-soft-tissue-sarcoma
#1
Cheuh-Chuan Yen, Tom Wei-Wu Chen
Soft tissue sarcoma (STS) is a heterogeneous disease with more than 50 subtypes. Once the disease reached locally advanced or metastatic status, the standard treatment remains to be chemotherapy. Current understanding of the underlying molecular and genomic mechanisms of different histology subtypes have led to encouraging development of new drugs in treating STS. Besides molecular targeted therapy, immunotherapy have also shown promising advancement in solid tumor treatments. This review will be in two parts...
August 2018: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/30111819/inhibition-of-histone-lysine-specific-demethylase-1-elicits-breast-tumor-immunity-and-enhances-antitumor-efficacy-of-immune-checkpoint-blockade
#2
Ye Qin, Shauna N Vasilatos, Lin Chen, Hao Wu, Zhishen Cao, Yumei Fu, Min Huang, Anda M Vlad, Binfeng Lu, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Immunotherapy strategies have been emerging as powerful weapons against cancer. Early clinical trials reveal that overall response to immunotherapy is low in breast cancer patients, suggesting that effective strategies to overcome resistance to immunotherapy are urgently needed. In this study, we investigated whether epigenetic reprograming by modulating histone methylation could enhance effector T lymphocyte trafficking and improve therapeutic efficacy of immune checkpoint blockade in breast cancer with focus on triple-negative breast cancer (TNBC) subtype...
August 15, 2018: Oncogene
https://www.readbyqxmd.com/read/30021161/alix-regulates-tumor-mediated-immunosuppression-by-controlling-egfr-activity-and-pd-l1-presentation
#3
James Monypenny, Hanna Milewicz, Fabian Flores-Borja, Gregory Weitsman, Anthony Cheung, Ruhe Chowdhury, Thomas Burgoyne, Appitha Arulappu, Katherine Lawler, Paul R Barber, Jose M Vicencio, Melanie Keppler, Wahyu Wulaningsih, Sean M Davidson, Franca Fraternali, Natalie Woodman, Mark Turmaine, Cheryl Gillett, Dafne Franz, Sergio A Quezada, Clare E Futter, Alex Von Kriegsheim, Walter Kolch, Borivoj Vojnovic, Jeremy G Carlton, Tony Ng
The immunosuppressive transmembrane protein PD-L1 was shown to traffic via the multivesicular body (MVB) and to be released on exosomes. A high-content siRNA screen identified the endosomal sorting complexes required for transport (ESCRT)-associated protein ALIX as a regulator of both EGFR activity and PD-L1 surface presentation in basal-like breast cancer (BLBC) cells. ALIX depletion results in prolonged and enhanced stimulation-induced EGFR activity as well as defective PD-L1 trafficking through the MVB, reduced exosomal secretion, and its redistribution to the cell surface...
July 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29971065/prostaglandin-e2-stimulates-the-expansion-of-regulatory-hematopoietic-stem-and-progenitor-cells-in-type-1-diabetes
#4
Moufida Ben Nasr, Francesca D'Addio, Amir Mohammad Malvandi, Silvia Faravelli, Eduardo Castillo-Leon, Vera Usuelli, Francesca Rocchio, Teresa Letizia, Abdel Basset El Essawy, Emma Assi, Chiara Mameli, Elisa Giani, Maddalena Macedoni, Anna Maestroni, Alice Dassano, Cristian Loretelli, Moira Paroni, Giuseppe Cannalire, Giacomo Biasucci, Marco Sala, Alessandra Biffi, Gian Vincenzo Zuccotti, Paolo Fiorina
Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29744030/tumor-cells-versus-host-immune-cells-whose-pd-l1-contributes-to-pd-1-pd-l1-blockade-mediated-cancer-immunotherapy
#5
Fei Tang, Pan Zheng
Antibody blockade of the PD-1/PD-L1 pathway has elicited durable antitumor responses in the therapy of a broad spectrum of cancers. PD-L1 is constitutively expressed in certain tumors and host immune cells, and its expression can be induced or maintained by many factors. The expression of PD-L1 on tumor tissues has been reported to be positively correlated with the efficacy of anti-PD-1/PD-L1 therapy in patients. However, multiple clinical trials indicate that patients with PD-L1-negative tumors also respond to this blockade therapy, which suggests the potential contribution of PD-L1 from host immune cells...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/29480817/cancer-vaccine-formulation-dictates-synergy-with-ctla-4-and-pd-l1-checkpoint-blockade-therapy
#6
Yared Hailemichael, Amber Woods, Tihui Fu, Qiuming He, Michael C Nielsen, Farah Hasan, Jason Roszik, Zhilan Xiao, Christina Vianden, Hiep Khong, Manisha Singh, Meenu Sharma, Faisal Faak, Derek Moore, Zhimin Dai, Scott M Anthony, Kimberly S Schluns, Padmanee Sharma, Victor H Engelhard, Willem W Overwijk
Anticancer vaccination is a promising approach to increase the efficacy of cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) checkpoint blockade therapies. However, the landmark FDA registration trial for anti-CTLA-4 therapy (ipilimumab) revealed a complete lack of benefit of adding vaccination with gp100 peptide formulated in incomplete Freund's adjuvant (IFA). Here, using a mouse model of melanoma, we found that gp100 vaccination induced gp100-specific effector T cells (Teffs), which dominantly forced trafficking of anti-CTLA-4-induced, non-gp100-specific Teffs away from the tumor, reducing tumor control...
April 2, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29416107/presence-of-high-endothelial-venules-correlates-with-a-favorable-immune-microenvironment-in-oral-squamous-cell-carcinoma
#7
Anna Maria Wirsing, Ida Korsnes Ervik, Marit Seppola, Lars Uhlin-Hansen, Sonja Eriksson Steigen, Elin Hadler-Olsen
Oral squamous cell carcinomas are associated with a poor prognosis, which may be partly due to functional impairment of the immune response. Lymphocyte recruitment to the tumor site is facilitated by high-endothelial venules, whereas expression of programmed-death ligand 1 (PD-L1) can impair T-cell function. Thus, we hypothesize that these factors are important in shaping the immune response in oral squamous cell carcinoma. In the present study, we characterized the immune infiltrate in formalin-fixed, paraffin-embedded tumor samples from 75 oral squamous cell carcinoma patients...
June 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29337303/pd-l1-on-host-cells-is-essential-for-pd-l1-blockade-mediated-tumor-regression
#8
Haidong Tang, Yong Liang, Robert A Anders, Janis M Taube, Xiangyan Qiu, Aditi Mulgaonkar, Xin Liu, Susan M Harrington, Jingya Guo, Yangchun Xin, Yahong Xiong, Kien Nham, William Silvers, Guiyang Hao, Xiankai Sun, Mingyi Chen, Raquibul Hannan, Jian Qiao, Haidong Dong, Hua Peng, Yang-Xin Fu
Programmed death-ligand 1 (PD-L1) expression on tumor cells is essential for T cell impairment, and PD-L1 blockade therapy has shown unprecedented durable responses in several clinical studies. Although higher expression of PD-L1 on tumor cells is associated with a better immune response after Ab blockade, some PD-L1-negative patients also respond to this therapy. In the current study, we explored whether PD-L1 on tumor or host cells was essential for anti-PD-L1-mediated therapy in 2 different murine tumor models...
February 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28483787/a-sting-agonist-given-with-ox40-receptor-and-pd-l1-modulators-primes-immunity-and-reduces-tumor-growth-in-tolerized-mice
#9
Jeremy B Foote, Marleen Kok, James M Leatherman, Todd D Armstrong, Bridget C Marcinkowski, Laureen S Ojalvo, David B Kanne, Elizabeth M Jaffee, Thomas W Dubensky, Leisha A Emens
Stimulator of interferon genes (STING) signaling induces IFNβ production by intratumoral dendritic cells (DC), driving T-cell priming and recruitment into the tumor microenvironment (TME). We examined to what extent preexisting antigen-specific tolerance influenced the efficacy of in situ delivery of a potent STING-activating cyclic dinucleotide (CDN), ADU S-100, against established HER-2+ breast tumors. ADU S-100 induced HER-2-specific CD8+ T-cell priming and durable tumor clearance in 100% of nontolerant parental FVB/N mice...
June 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28345023/enhancement-of-psma-directed-car-adoptive-immunotherapy-by-pd-1-pd-l1-blockade
#10
Inna Serganova, Ekaterina Moroz, Ivan Cohen, Maxim Moroz, Mayuresh Mane, Juan Zurita, Larissa Shenker, Vladimir Ponomarev, Ronald Blasberg
Chimeric antigen receptor (CAR) T cell therapy in hematologic malignancies has shown remarkable responses, but the same level of success has not been observed in solid tumors. A new prostate cancer model (Myc-CaP:PSMA(+)) and a second-generation anti-hPSMA human CAR T cells expressing a Click Beetle Red luciferase reporter) were used to study hPSMA targeting and assess CAR T cell trafficking and persistence by bioluminescence imaging (BLI). We investigated the antitumor efficacy of human CAR T cells targeting human prostate-specific membrane antigen (hPSMA), in the presence and absence of the target antigen; first alone and then combined with a monoclonal antibody targeting the human programmed death receptor 1 (anti-hPD1 mAb)...
March 17, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27911948/tlr3-induced-maturation-of-murine-dendritic-cells-regulates-ctl-responses-by-modulating-pd-l1-trafficking
#11
Aditi Varthaman, Hélène D Moreau, Mathieu Maurin, Philippe Benaroch
Targeting TLR3 through formulations of polyI:C is widely studied as an adjuvant in cancer immunotherapy. The efficacy of such targeting has been shown to increase in combination with anti-PD-L1 treatment. Nevertheless, the mechanistic details of the effect of polyI:C on DC maturation and the impact on T-DC interactions upon PD-L1 blockade is largely unknown. Here we found that although DC treatment with polyI:C induced a potent inflammatory response including the production of type I interferon, polyI:C treatment of DCs impaired activation of peptide specific CD8+ T cells mainly due to PD-L1...
2016: PloS One
https://www.readbyqxmd.com/read/27867386/immune-regulation-by-pericytes-modulating-innate-and-adaptive-immunity
#12
REVIEW
Rocío Navarro, Marta Compte, Luis Álvarez-Vallina, Laura Sanz
Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27836246/emerging-role-of-immunotherapy-in-urothelial-carcinoma-immunobiology-biomarkers
#13
REVIEW
Randy F Sweis, Matthew D Galsky
Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement...
December 2016: Urologic Oncology
https://www.readbyqxmd.com/read/27699239/multiparametric-profiling-of-non-small-cell-lung-cancers-reveals-distinct-immunophenotypes
#14
Patrick H Lizotte, Elena V Ivanova, Mark M Awad, Robert E Jones, Lauren Keogh, Hongye Liu, Ruben Dries, Christina Almonte, Grit S Herter-Sprie, Abigail Santos, Nora B Feeney, Cloud P Paweletz, Meghana M Kulkarni, Adam J Bass, Anil K Rustgi, Guo-Cheng Yuan, Donald W Kufe, Pasi A Jänne, Peter S Hammerman, Lynette M Sholl, F Stephen Hodi, William G Richards, Raphael Bueno, Jessie M English, Mark A Bittinger, Kwok-Kin Wong
BACKGROUND. Immune checkpoint blockade improves survival in a subset of patients with non-small-cell lung cancer (NSCLC), but robust biomarkers that predict response to PD-1 pathway inhibitors are lacking. Furthermore, our understanding of the diversity of the NSCLC tumor immune microenvironment remains limited. METHODS. We performed comprehensive flow cytometric immunoprofiling on both tumor and immune cells from 51 NSCLCs and integrated this analysis with clinical and histopathologic characteristics, next-generation sequencing, mRNA expression, and PD-L1 immunohistochemistry (IHC)...
September 8, 2016: JCI Insight
https://www.readbyqxmd.com/read/27656680/pd-1-pathway-mediated-regulation-of-islet-specific-cd4-t-cell-subsets-in-autoimmune-diabetes
#15
Tijana Martinov, Justin A Spanier, Kristen E Pauken, Brian T Fife
Type 1 diabetes (T1D) is a CD4(+) T cell-driven autoimmune disease resulting from the destruction of insulin-producing pancreatic beta cells. Clinical evidence and studies in non-obese diabetic (NOD) mice suggest that insulin is a major autoantigen. With this in mind, we developed insulin B10-23:IA(g7) tetramer reagents to track insulin-specific CD4(+) T cells in mice and interrogated the role of Programmed death-1 (PD-1) for peripheral tolerance. PD-1 is a T cell inhibitory receptor necessary to maintain tolerance and prevent T1D in NOD mice...
2016: Immunoendocrinology (Houston, Tex.)
https://www.readbyqxmd.com/read/27589875/response-to-programmed-cell-death-1-blockade-in-a-murine-melanoma-syngeneic-model-requires-costimulation-cd4-and-cd8-t-cells
#16
Blanca Homet Moreno, Jesse M Zaretsky, Angel Garcia-Diaz, Jennifer Tsoi, Giulia Parisi, Lidia Robert, Katrina Meeth, Abibatou Ndoye, Marcus Bosenberg, Ashani T Weeraratna, Thomas G Graeber, Begoña Comin-Anduix, Siwen Hu-Lieskovan, Antoni Ribas
The programmed cell death protein 1 (PD-1) limits effector T-cell functions in peripheral tissues, and its inhibition leads to clinical benefit in different cancers. To better understand how PD-1 blockade therapy modulates the tumor-host interactions, we evaluated three syngeneic murine tumor models, the BRAFV600E -driven YUMM1.1 and YUMM2.1 melanomas, and the carcinogen-induced murine colon adenocarcinoma MC38. The YUMM cell lines were established from mice with melanocyte-specific BRAFV600E mutation and PTEN loss (BRAFV600E /PTEN-/- )...
October 2016: Cancer Immunology Research
https://www.readbyqxmd.com/read/27571927/atezolizumab-in-combination-with-bevacizumab-enhances-antigen-specific-t-cell-migration-in-metastatic-renal-cell-carcinoma
#17
RANDOMIZED CONTROLLED TRIAL
Jeffrey J Wallin, Johanna C Bendell, Roel Funke, Mario Sznol, Konstanty Korski, Suzanne Jones, Genevive Hernandez, James Mier, Xian He, F Stephen Hodi, Mitchell Denker, Vincent Leveque, Marta Cañamero, Galina Babitski, Hartmut Koeppen, James Ziai, Neeraj Sharma, Fabien Gaire, Daniel S Chen, Daniel Waterkamp, Priti S Hegde, David F McDermott
Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC...
August 30, 2016: Nature Communications
https://www.readbyqxmd.com/read/26723878/current-progress-in-immunotherapy-for-pancreatic-cancer
#18
REVIEW
Kelly Foley, Victoria Kim, Elizabeth Jaffee, Lei Zheng
Pancreatic cancer remains one of the most lethal cancers with few treatment options. Immune-based strategies to treat pancreatic cancer, such as immune checkpoint inhibitors, therapeutic vaccines, and combination immunotherapies, are showing promise where other approaches have failed. Immune checkpoint inhibitors, including anti-CTLA4, anti-PD-1, and anti-PD-L1 antibodies, are effective as single agents in immune sensitive cancers like melanoma, but lack efficacy in immune insensitive cancers including pancreatic cancer...
October 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/26503055/epigenetic-silencing-of-th1-type-chemokines-shapes-tumour-immunity-and-immunotherapy
#19
Dongjun Peng, Ilona Kryczek, Nisha Nagarsheth, Lili Zhao, Shuang Wei, Weimin Wang, Yuqing Sun, Ende Zhao, Linda Vatan, Wojciech Szeliga, Jan Kotarski, Rafał Tarkowski, Yali Dou, Kathleen Cho, Sharon Hensley-Alford, Adnan Munkarah, Rebecca Liu, Weiping Zou
Epigenetic silencing including histone modifications and DNA methylation is an important tumorigenic mechanism. However, its role in cancer immunopathology and immunotherapy is poorly understood. Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment...
November 12, 2015: Nature
https://www.readbyqxmd.com/read/25979549/immune-targeting-in-breast-cancer
#20
REVIEW
Ashley Cimino-Mathews, Jeremy B Foote, Leisha A Emens
The immune system is active in breast cancer, playing a dual role in tumor progression and in immune surveillance. Infiltrating immune cells are both prognostic and predictive of response to standard breast cancer therapies. Breast cancer vaccines can activate and expand tumor-specific T cells, but have enjoyed minimal clinical success to date. Immune checkpoint blockade is a new approach to cancer immunotherapy, with documented clinical responses in diverse tumor types. Interest in breast cancer immunotherapy has been reignited by recent reports of objective responses in metastatic triple-negative breast cancer with both pembrolizumab (a programmed cell death protein 1 [PD-1] antagonist) and MPDL3280A (a programmed cell death ligand 1 [PD-L1] antagonist)...
May 2015: Oncology (Williston Park, NY)
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