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Colon Liver PD-L1

Hua Jing, Michael Hettich, Simone Gaedicke, Elke Firat, Mark Bartholomä, Gabriele Niedermann
BACKGROUND: Immunogenic radiotherapy (RT) can act synergistically with immune checkpoint blockers (ICBs). However, alternatives are needed for non-responding patients and those with pre-existing or ICB-induced autoimmune symptoms. Combination of RT with IL-2 could be an alternative. But IL-2 has a short half-life, and, by binding to its high-affinity receptor, it strongly stimulates immunosuppressive CD4+ Tregs and seems to promote potentially life-threatening vascular leakage. IL-2/anti-IL-2 complexes (IL-2c), which bind to the low-affinity receptor, have been reported to circumvent these disadvantages but they have not yet been thoroughly tested in conjunction with radiotherapy...
February 26, 2019: Journal for Immunotherapy of Cancer
Shinkichi Takamori, Kazuki Takada, Tetsuzo Tagawa, Gouji Toyokawa, Fumihiko Hirai, Nami Yamashita, Tatsuro Okamoto, Eiji Oki, Tomoharu Yoshizumi, Yoshinao Oda, Yoshihiko Maehara
BACKGROUND: It has been reported that the tumor microenvironment, including tumor-associated immune cells (ICs) and programmed cell death-ligand 1 (PD-L1) expression, differs between primary and metastatic tumors. This study aimed to elucidate the differences in PD-L1 expression on tumor cells (TCs) and ICs between lung metastases and corresponding primary tumors. METHODS: We analyzed paired lesions from 44 patients diagnosed with lung metastases between 2005 and 2017 at Kyushu University...
December 2018: Surgical Oncology
Jacqueline Wyss, Bastian Dislich, Viktor H Koelzer, José A Galván, Heather Dawson, Marion Hädrich, Daniel Inderbitzin, Alessandro Lugli, Inti Zlobec, Martin D Berger
INTRODUCTION: The programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays an important role in controlling immune suppression by down-regulating T effector cell activities, enabling tumor cells to escape from the host's antitumor immunsurveillance. While only a small part of colon cancer cells express PD-L1, we sought to evaluate the differential impact of stromal and epithelial PD-L1 expression of primary tumors and liver metastasis on overall survival (OS) in colon cancer patients...
September 21, 2018: Clinical Colorectal Cancer
Frank Stephen Hodi, Vanna Chiarion-Sileni, Rene Gonzalez, Jean-Jacques Grob, Piotr Rutkowski, Charles Lance Cowey, Christopher D Lao, Dirk Schadendorf, John Wagstaff, Reinhard Dummer, Pier Francesco Ferrucci, Michael Smylie, Andrew Hill, David Hogg, Ivan Marquez-Rodas, Joel Jiang, Jasmine Rizzo, James Larkin, Jedd D Wolchok
BACKGROUND: Previously reported results from the phase 3 CheckMate 067 trial showed a significant improvement in objective responses, progression-free survival, and overall survival with nivolumab plus ipilimumab or nivolumab alone compared with ipilimumab alone in patients with advanced melanoma. The aim of this report is to provide 4-year updated efficacy and safety data from this study. METHODS: In this phase 3 trial, eligible patients were aged 18 years or older with previously untreated, unresectable, stage III or stage IV melanoma, known BRAFV600 mutation status, and an Eastern Cooperative Oncology Group performance status of 0 or 1...
November 2018: Lancet Oncology
Aaron Sosa, Esther Lopez Cadena, Cristina Simon Olive, Niki Karachaliou, Rafael Rosell
Immunotherapy through checkpoint inhibitors is now standard practice for a growing number of cancer types, supported by overall improvement of clinical outcomes and better tolerance. One anti-CTLA-4 antibody (ipilimumab), two anti-PD-1 antibodies (pembrolizumab and nivolumab) and three anti-PD-L1 antibodies (atezolizumab, avelumab and durvalumab) have been approved for clear benefits across diverse trials. Adverse events of an immune nature associated with these agents frequently affect the skin, colon, endocrine glands, lungs and liver...
2018: Therapeutic Advances in Medical Oncology
Kathryn W Juchem, Faruk Sacirbegovic, Cuiling Zhang, Arlene H Sharpe, Kerry Russell, Jennifer M McNiff, Anthony J Demetris, Mark J Shlomchik, Warren D Shlomchik
Effector memory T cells (TEM ) are less capable of inducing graft-versus-host disease (GVHD) compared with naive T cells (TN ). Previously, in the TS1 TCR transgenic model of GVHD, wherein TS1 CD4 cells specific for a model minor histocompatibility Ag (miHA) induce GVHD in miHA-positive recipients, we found that cell-intrinsic properties of TS1 TEM reduced their GVHD potency relative to TS1 TN Posttransplant, TS1 TEM progeny expressed higher levels of PD-1 than did TS1 TN progeny, leading us to test the hypothesis that TEM induce less GVHD because of increased sensitivity to PD-ligands...
January 15, 2018: Journal of Immunology
Asim Saha, Kazutoshi Aoyama, Patricia A Taylor, Brent H Koehn, Rachelle G Veenstra, Angela Panoskaltsis-Mortari, David H Munn, William J Murphy, Miyuki Azuma, Hideo Yagita, Brian T Fife, Mohammed H Sayegh, Nader Najafian, Gerard Socie, Rafi Ahmed, Gordon J Freeman, Arlene H Sharpe, Bruce R Blazar
Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, play an important role in the maintenance of peripheral tolerance. We explored the role of PD-1 ligands in regulating graft-versus-host disease (GVHD). Both PD-L1 and PD-L2 expression were upregulated in the spleen, liver, colon, and ileum of GVHD mice. Whereas PD-L2 expression was limited to hematopoietic cells, hematopoietic and endothelial cells expressed PD-L1. PD-1/PD-L1, but not PD-1/PD-L2, blockade markedly accelerated GVHD-induced lethality...
October 24, 2013: Blood
Zhang Wenjin, Peng Chuanhui, Wan Yunle, Shaikh Abdul Lateef, Zheng Shusen
BACKGROUND: Controversy exists regarding the role of PD1 and its ligand PD-L1 in chronic hepatitis B infection. In some studies, persistent HBV infection has been attributed to high levels of PD-1 and PD-L1 expression on HBV-specific T-cells and antigen-presenting cells (APCs) respectively. Other studies revealed that the up-regulation of PD-1 and PD-L1 during an acute inflammation phase is required to offset increasing positive co-stimulatory signals to avoid severe damage by an over-vigorous immune response...
2012: BMC Gastroenterology
Asís Palazón, Iván Martínez-Forero, Alvaro Teijeira, Aizea Morales-Kastresana, Carlos Alfaro, Miguel F Sanmamed, Jose Luis Perez-Gracia, Iván Peñuelas, Sandra Hervás-Stubbs, Ana Rouzaut, Manuel Ortiz de Landázuri, Maria Jure-Kunkel, Julian Aragonés, Ignacio Melero
UNLABELLED: The tumor microenvironment of transplanted and spontaneous mouse tumors is profoundly deprived of oxygenation as confirmed by positron emission tomographic (PET) imaging. CD8 and CD4 tumor-infiltrating T lymphocytes (TIL) of transplanted colon carcinomas, melanomas, and spontaneous breast adenocarcinomas are CD137 (4-1BB)-positive, as opposed to their counterparts in tumor-draining lymph nodes and spleen. Expression of CD137 on activated T lymphocytes is markedly enhanced by hypoxia and the prolyl-hydroxylase inhibitor dimethyloxalylglycine (DMOG)...
July 2012: Cancer Discovery
Yoshiko Iwai, Seigo Terawaki, Tasuku Honjo
Since metastasis is the major cause of death for cancer patients, there is an urgent need to develop new therapies to control hematogenous dissemination of cancer cells. Previously we and others demonstrated a novel mechanism that allows tumors to escape from the host immune response by expressing PD-L1 which can negatively regulate immune response through the interaction with PD-1, an immunoinhibitory receptor belonging to the CD28 family. In this study, we report that hematogenous spread of poorly immunogenic B16 melanoma cells to the liver was inhibited in PD-1-deficient mice...
February 2005: International Immunology
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