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https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#1
Yanheng Wu, Mingshui Chen, Peihong Wu, Chen Chen, Zhi Ping Xu, Wenyi Gu
Here we report the expression of programmed cell death ligand 1/2 (PD-L1/L2) in breast and colon cancer stem cells (CSCs). The stemness of these cells was confirmed by their surface markers. Using flow cytometry analysis we demonstrated that PD-L1 expression was higher in CSCs of both cancers compared to non-stem like cancer cells. Consistent with this, detection of cellular PD-L1 proteins by Western blot assay also showed increased PD-L1 protein in CSCs. In contrast, only trance amounts of PD-L2 were detected in CSCs of both cancers...
January 20, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28103263/splenic-cd4-t-cells-in-progressive-visceral-leishmaniasis-show-a-mixed-effector-regulatory-phenotype-and-impair-macrophage-effector-function-through-inhibitory-receptor-expression
#2
Audrie A Medina-Colorado, Elvia Y Osorio, Omar A Saldarriaga, Bruno L Travi, Fanping Kong, Heidi Spratt, Lynn Soong, Peter C Melby
Visceral leishmaniasis (VL), caused by infection with the intracellular protozoan Leishmania donovani, is a chronic progressive disease with a relentlessly increasing parasite burden in the spleen, liver and bone marrow. The disease is characterized by fever, splenomegaly, cachexia, and pancytopenia, and progresses to death if not treated. Control of Leishmania infection is mediated by Th1 (IFNγ-producing) CD4+ T cells, which activate macrophages to produce nitric oxide and kill intracellular parasites. However, despite expansion of CD4+ T cells and increased IFNγ expression in the spleen, humans with active VL do not control the infection...
2017: PloS One
https://www.readbyqxmd.com/read/28096717/immune-checkpoint-inhibitors-in-the-era-of-precision-medicine-what-radiologists-should-know
#3
REVIEW
Marta Braschi-Amirfarzan, Sree Harsha Tirumani, Frank Stephen Hodi, Mizuki Nishino
Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events...
January 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28094319/helminth-induced-ly6c-hi-monocyte-derived-alternatively-activated-macrophages-suppress-experimental-autoimmune-encephalomyelitis
#4
Cesar Terrazas, Juan de Dios Ruiz-Rosado, Stephanie A Amici, Kyle A Jablonski, Diana Martinez-Saucedo, Lindsay M Webb, Hanna Cortado, Frank Robledo-Avila, Steve Oghumu, Abhay R Satoskar, Miriam Rodriguez-Sosa, Luis I Terrazas, Mireia Guerau-de-Arellano, Santiago Partida-Sánchez
Helminths cause chronic infections and affect the immune response to unrelated inflammatory diseases. Although helminths have been used therapeutically to ameliorate inflammatory conditions, their anti-inflammatory properties are poorly understood. Alternatively activated macrophages (AAMϕs) have been suggested as the anti-inflammatory effector cells during helminth infections. Here, we define the origin of AAMϕs during infection with Taenia crassiceps, and their disease-modulating activity on the Experimental Autoimmune Encephalomyelitis (EAE)...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28086852/pd-l1-expression-in-papillary-renal-cell-carcinoma
#5
Takanobu Motoshima, Yoshihiro Komohara, Chaoya Ma, Arni Kusuma Dewi, Hirotsugu Noguchi, Sohsuke Yamada, Toshiyuki Nakayama, Shohei Kitada, Yoshiaki Kawano, Wataru Takahashi, Masaaki Sugimoto, Motohiro Takeya, Naohiro Fujimoto, Yoshinao Oda, Masatoshi Eto
BACKGROUND: The immune escape or tolerance of cancer cells is considered to be closely involved in cancer progression. Programmed death-1 (PD-1) is an inhibitory receptor expressed on activating T cells, and several types of cancer cells were found to express PD-1 ligand 1 (PD-L1) and ligand 2 (PD-L2). METHODS: In the present study, we investigated PD-L1/2 expression in papillary renal cell carcinoma (pRCC). RESULT: We found PD-L1 expression in 29 of 102 cases, but no PD-L2 expression was seen...
January 13, 2017: BMC Urology
https://www.readbyqxmd.com/read/28074937/circulating-t-lymphocyte-subsets-cytokines-and-immune-checkpoint-inhibitors-in-patients-with-bipolar-ii-or-major-depression-a-preliminary-study
#6
Wei Wu, Ya-Li Zheng, Li-Ping Tian, Jian-Bo Lai, Chan-Chan Hu, Peng Zhang, Jing-Kai Chen, Jian-Bo Hu, Man-Li Huang, Ning Wei, Wei-Juan Xu, Wei-Hua Zhou, Shao-Jia Lu, Jing Lu, Hong-Li Qi, Dan-Dan Wang, Xiao-Yi Zhou, Jin-Feng Duan, Yi Xu, Shao-Hua Hu
This study aimed to investigate the less known activation pattern of T lymphocyte populations and immune checkpoint inhibitors on immunocytes in patients with bipolar II disorder depression (BD) or major depression (MD). A total of 23 patients with BD, 22 patients with MD, and 20 healthy controls (HCs) were recruited. The blood cell count of T lymphocyte subsets and the plasma level of cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were selectively investigated. The expression of T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, on T lymphocytes and monocytes, was detected...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28052400/programmed-death-1-ligand-1-and-2-expression-in-cutaneous-squamous-cell-carcinoma-and-their-relationship-with-tumor-infiltrating-dendritic-cells
#7
Qingqing Jiao, Cuiping Liu, Wenzhong Li, Wei Li, Fuming Fang, Qihong Qian, Xueguang Zhang
The Programmed Death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are costimulatory molecules that contribute to the negative regulation of T-lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumor infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyze PD-L1 and PD-L2 expression and dendritic cells (DCs) infiltration in tumor tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a, and CD83 in 61 CSCC tissues...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28018348/pd-l1-is-not-constitutively-expressed-on-tasmanian-devil-facial-tumor-cells-but-is-strongly-upregulated-in-response-to-ifn-%C3%AE-and-can-be-expressed-in-the-tumor-microenvironment
#8
Andrew S Flies, A Bruce Lyons, Lynn M Corcoran, Anthony T Papenfuss, James M Murphy, Graeme W Knowles, Gregory M Woods, John D Hayball
The devil facial tumor disease (DFTD) is caused by clonal transmissible cancers that have led to a catastrophic decline in the wild Tasmanian devil (Sarcophilus harrisii) population. The first transmissible tumor, now termed devil facial tumor 1 (DFT1), was first discovered in 1996 and has been continually transmitted to new hosts for at least 20 years. In 2015, a second transmissible cancer [devil facial tumor 2 (DFT2)] was discovered in wild devils, and the DFT2 is genetically distinct and independent from the DFT1...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28018338/the-pd1-pd-l1-2-pathway-from-discovery-to-clinical-implementation
#9
REVIEW
Kankana Bardhan, Theodora Anagnostou, Vassiliki A Boussiotis
The immune system maintains a critically organized network to defend against foreign particles, while evading self-reactivity simultaneously. T lymphocytes function as effectors and play an important regulatory role to orchestrate the immune signals. Although central tolerance mechanism results in the removal of the most of the autoreactive T cells during thymic selection, a fraction of self-reactive lymphocytes escapes to the periphery and pose a threat to cause autoimmunity. The immune system evolved various mechanisms to constrain such autoreactive T cells and maintain peripheral tolerance, including T cell anergy, deletion, and suppression by regulatory T cells (TRegs)...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28002729/the-heterogeneity-of-ly6c-hi-monocytes-controls-their-differentiation-into-inos-macrophages-or-monocyte-derived-dendritic-cells
#10
Shinelle Menezes, Daisy Melandri, Giorgio Anselmi, Thibaut Perchet, Jakob Loschko, Juan Dubrot, Rajen Patel, Emmanuel L Gautier, Stéphanie Hugues, M Paula Longhi, Jake Y Henry, Sergio A Quezada, Grégoire Lauvau, Ana-Maria Lennon-Duménil, Enrique Gutiérrez-Martínez, Alain Bessis, Elisa Gomez-Perdiguero, Christian E Jacome-Galarza, Hannah Garner, Frederic Geissmann, Rachel Golub, Michel C Nussenzweig, Pierre Guermonprez
Inflammation triggers the differentiation of Ly6C(hi) monocytes into microbicidal macrophages or monocyte-derived dendritic cells (moDCs). Yet, it is unclear whether environmental inflammatory cues control the polarization of monocytes toward each of these fates or whether specialized monocyte progenitor subsets exist before inflammation. Here, we have shown that naive monocytes are phenotypically heterogeneous and contain an NR4A1- and Flt3L-independent, CCR2-dependent, Flt3(+)CD11c(-)MHCII(+)PU.1(hi) subset...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27999753/pd-l1-pd-l2-and-pd-1-expression-in-metastatic-melanoma-correlation-with-tumor-infiltrating-immune-cells-and-clinical-outcome
#11
Joseph M Obeid, Gulsun Erdag, Mark E Smolkin, Donna H Deacon, James W Patterson, Leiping Chen, Timothy N Bullock, Craig L Slingluff
Therapeutic blockade of PD-1/PD-L1 can have dramatic therapeutic benefit in some patients; however, the prognostic associations of PD-1 and its ligands, in the absence of therapeutic blockade have not been definitively addressed. In particular, associations of PD-L2 with immune infiltrates and with outcome have yet to be explored. We hypothesized that surface expression of both PD-L1 and PD-L2 by melanoma cells would be associated with immune cell infiltration and with overall patient survival, independent of checkpoint blockade therapy...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27999734/molecular-and-clinical-characterization-of-pd-l1-expression-at-transcriptional-level-via-976-samples-of-brain-glioma
#12
Zheng Wang, Chuanbao Zhang, Xing Liu, Zhiliang Wang, Lihua Sun, Guanzhang Li, Jingshan Liang, Huimin Hu, Yanwei Liu, Wei Zhang, Tao Jiang
Background: PD-L1 has been widely reported as immune check points in a range of malignancies as well as some immune-originated diseases. In glioma, the role of PD-L1 remains unclear. We aimed at investigating its role at transcriptome level and relationship with clinical practice. Method and patients: In total, 976 glioma samples with transcriptome data, including 301 microarray data from Chinese Glioma Genome Atlas (CGGA project) and 675 RNAseq data from TCGA project, were enrolled into our study. Clinical and IDH mutation data were also available...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27991907/immunomodulating-property-of-mapk-inhibitors-from-translational-knowledge-to-clinical-implementation
#13
Mario Mandalà, Francesco De Logu, Barbara Merelli, Romina Nassini, Daniela Massi
Treatment of metastatic melanoma was radically changed by the introduction of inhibitors of BRAF, an oncogene mutated in 40-50% of patients. Another area of advancement was the use of immunotherapy, and specifically, immune checkpoint inhibitors. There is compelling evidence that oncogenic BRAF, in addition to driving melanoma proliferation, differentiation and survival, induces T-cell suppression directly through the secretion of inhibitory cytokines or through membrane expression of co-inhibitory molecules such as the PD-1 ligands PD-L1 or PD-L2...
December 19, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27942391/metastatic-basal-cell-carcinoma-with-amplification-of-pd-l1-exceptional-response-to-anti-pd1-therapy
#14
Sadakatsu Ikeda, Aaron M Goodman, Philip R Cohen, Taylor J Jensen, Christopher K Ellison, Garrett Frampton, Vincent Miller, Sandip P Patel, Razelle Kurzrock
Metastatic basal cell carcinomas are rare malignancies harbouring Hedgehog pathway alterations targetable by SMO antagonists (vismodegib/sonidegib). We describe, for the first time, the molecular genetics and response of a patient with Hedgehog inhibitor-resistant metastatic basal cell carcinoma who achieved rapid tumour regression (ongoing near complete remission at 4 months) with nivolumab (anti-PD1 antibody). He had multiple hallmarks of anti-PD1 responsiveness including high mutational burden (> 50 mutations per megabase; 19 functional alterations in tissue next-generation sequencing (NGS; 315 genes)) as well as PDL1/PDL2/JAK2 amplification (as determined by both tissue NGS and by analysis of plasma-derived cell-free DNA)...
2016: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/27924827/pd-1-pd-l-pathway-inhibits-m-tb-specific-cd4-t-cell-functions-and-phagocytosis-of-macrophages-in-active-tuberculosis
#15
Lei Shen, Yan Gao, Yuanyuan Liu, Bingyan Zhang, Qianqian Liu, Jing Wu, Lin Fan, Qinfang Ou, Wenhong Zhang, Lingyun Shao
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27921410/downregulation-of-immunosuppressive-molecules-pd-1-and-pd-l1-but-not-pd-l2-in-the-patients-with-multiple-sclerosis
#16
Mohammad Reza Javan, Saeed Aslani, Mohammad Reza Zamani, Javad Rostamnejad, Milad Asadi, Mahdi Farhoodi, Mohammad Hossein Nicknam
Programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2, have been regarded as important immune system regulatory molecules. The aberrant expression of the molecules has been related to several autoimmune disorders. This study is aimed to assess the mRNA expression level of PD-1, PD-L1, and PD-L2 molecules in the peripheral blood mononuclear mells (PBMCs) from multiple sclerosis (MS) patients. PBMCs were isolated from the whole blood of 50 MS and 50 healthy individuals. Total RNA content of the leukocytes was extracted...
August 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/27881581/nivolumab-in-the-treatment-of-hodgkin-lymphoma
#17
Stephen M Ansell
Despite an extensive immune infiltrate that is recruited to the tumor by malignant Reed Sternberg cells in Hodgkin lymphoma, the antitumor immune response is ineffective and unable to eradicate the malignant cells. The ineffective immune response is in part due to PD-1 signaling that renders intratumoral immune cells anergic. Reed Sternberg cells have been shown to upregulate expression of the PD-1 ligands, PD-L1 and PD-L2, due to either genetic alterations at chromosome 9p24.1 or Epstein Barr virus infection, and these ligands suppress the function of PD-1+ intratumoral T-cells...
November 23, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27870715/posttranscriptional-control-of-pd-l1-expression-by-17%C3%AE-estradiol-via-pi3k-akt-signaling-pathway-in-er%C3%AE-positive-cancer-cell-lines
#18
Lingyun Yang, Feng Huang, Jiandong Mei, Xun Wang, Qiuyang Zhang, Hongjing Wang, Mingrong Xi, Zongbing You
OBJECTIVE: Estrogen is a well-known oncogenic driver in endometrial (ECs) and breast cancers (BCs). Programmed cell death protein 1 (PD-1) and its ligands PD-1 Ligand 1 (PD-L1) and PD-L2 have been shown to mediate immune evasion of the tumor cells. The purpose of the present study was to assess the effects of estrogen on PD-L1 and PD-L2 expression in EC and BC cell lines. METHODS: 17β-Estradiol (E2)-induced expression of PD-L1 and PD-L2 and possible signaling pathway were investigated in EC and BC cells...
November 17, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27867382/il-1%C3%AE-but-not-programed-death-1-and-programed-death-ligand-pathway-is-critical-for-the-human-th17-response-to-mycobacterium-tuberculosis
#19
Emmanuel Stephen-Victor, Varun Kumar Sharma, Mrinmoy Das, Anupama Karnam, Chaitrali Saha, Maxime Lecerf, Caroline Galeotti, Srinivas V Kaveri, Jagadeesh Bayry
The programed death-1 (PD-1)-programed death ligand-1 (PD-L1) and PD-L2 co-inhibitory pathway has been implicated in the evasion strategies of Mycobacterium tuberculosis. Specifically, M. tuberculosis-induced PD-L1 orchestrates expansion of regulatory T cells and suppression of Th1 response. However, the role of PD pathway in regulating Th17 response to M. tuberculosis has not been investigated. In the present report, we demonstrate that M. tuberculosis and M. tuberculosis-derived antigen fractions have differential abilities to mediate human monocyte- and dendritic cell (DC)-mediated Th17 response and were independent of expression of PD-L1 or PD-L2 on aforementioned antigen-presenting cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27861596/pd-l1-status-in-refractory-lymphomas
#20
Semir Vranic, Nilanjan Ghosh, Jeffery Kimbrough, Nurija Bilalovic, Ryan Bender, David Arguello, Yvonne Veloso, Aida Dizdarevic, Zoran Gatalica
Targeted immunotherapy based on PD-1/PD-L1 suppression has revolutionized the treatment of various solid tumors. A remarkable improvement has also been observed in the treatment of patients with refractory/relapsing classical Hodgkin lymphoma (cHL). We investigated PD-L1 status in a variety of treatment resistant lymphomas. Tumor samples from 78 patients with therapy resistant lymphomas were immunohistochemically (IHC) investigated for the expression of PD-L1 using two antibody clones (SP142 and SP263, Ventana)...
2016: PloS One
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