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https://www.readbyqxmd.com/read/28228279/loss-of-pten-is-associated-with-resistance-to-anti-pd-1-checkpoint-blockade-therapy-in-metastatic-uterine-leiomyosarcoma
#1
Suzanne George, Diana Miao, George D Demetri, Dennis Adeegbe, Scott J Rodig, Sachet Shukla, Mikel Lipschitz, Ali Amin-Mansour, Chandrajit P Raut, Scott L Carter, Peter Hammerman, Gordon J Freeman, Catherine J Wu, Patrick A Ott, Kwok-Kin Wong, Eliezer M Van Allen
Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28223102/inflammatory-cytokines-il-17-and-tnf-%C3%AE-up-regulate-pd-l1-expression-in-human-prostate-and-colon-cancer-cells
#2
Xun Wang, Lingyun Yang, Feng Huang, Qiuyang Zhang, Sen Liu, Lin Ma, Zongbing You
Programmed cell death protein 1 (PD-1) acts on PD-1 ligands (PD-L1 and PD-L2) to suppress activation of cytotoxic T lymphocytes. Interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) are co-expressed by T helper 17 (TH17) cells in many tumors. The purpose of this study was to test if IL-17 and TNF-α may synergistically induce PD-L1 expression in human prostate cancer LNCaP and human colon cancer HCT116 cell lines. We found that IL-17 did not induce PD-L1 mRNA expression, but up-regulated PD-L1 protein expression in HCT116 and LNCaP cells...
February 14, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28219001/glut1-as-a-prognostic-factor-for-classical-hodgkin-s-lymphoma-correlation-with-pd-l1-and-pd-l2-expression
#3
Young Wha Koh, Jae-Ho Han, Seong Yong Park, Dok Hyun Yoon, Cheolwon Suh, Jooryung Huh
Background: Glucose transporter type 1 (GLUT1) expression is linked to glucose metabolism and tissue hypoxia. A recent study reported that GLUT1 was significantly associated with programmed death ligand 1 (PD-L1) as a therapeutic target in relapsed or refractory classical Hodgkin's lymphoma (cHL). The purpose of this study was to measure the expression of GLUT1 and assess its prognostic significance and potential relationships with PD-L1, programmed death ligand 2 (PD-L2), and programmed death-1 (PD-1) expressions in cHL...
February 21, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28185924/high-throughput-dynamic-analysis-of-differentially-expressed-genes-in-splenic-dendritic-cells-from-mice-infected-with-schistosoma-japonicum
#4
Lin Chen, Qingzhou Chen, Wei Hou, Li He
Dendritic cells are the initiation and key point of immune response and play a role in immune regulation. So we explored the mechanisms involved in immune regulation of dendritic cells (DCs) against schistosomiasis using mice infected with Schistosoma japonicum. Splenic DCs from normal mice and mice with acute and chronic S. japonicum infection were sorted by flow cytometry. The numbers and functions of differentially expressed genes (DEGs) in DCs were determined by high-throughput analysis. All DEGs with transcription-level fold changes of ≥2 were selected and matched to corresponding genes in databases...
February 7, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28182273/association-of-time-varying-clearance-of-nivolumab-with-disease-dynamics-and-its-implications-on-exposure-response-analysis
#5
Chao Liu, Jingyu Yu, Hongshan Li, Jiang Liu, Yuan Xu, Pengfei Song, Qi Liu, Hong Zhao, James Xu, Virginia E Maher, Brian P Booth, Geoffrey Kim, Atiqur Rahman, Yaning Wang
Nivolumab is a human monoclonal antibody that blocks the interaction between PD-1 programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2. Nivolumab demonstrated efficacy in clinical trials for various types of cancer. A time-varying clearance was identified for nivolumab. We show that the change of clearance over time is associated with the post-treatment effects: clearance decreases when disease status improves. This interaction between post-treatment effects and drug exposure may lead to a biased steep estimate of exposure-response (E-R) relationship for efficacy...
February 9, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28169111/expression-pattern-of-immune-checkpoint-associated-molecules-in-radical-nephrectomy-specimens-as-a-prognosticator-in-patients-with-metastatic-renal-cell-carcinoma-treated-with-tyrosine-kinase-inhibitors
#6
Takuto Hara, Hideaki Miyake, Masato Fujisawa
OBJECTIVE: To analyze the expression pattern of immune checkpoint-associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). METHODS: Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining...
February 3, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28130401/distinctive-histogenesis-and-immunological-microenvironment-based-on-transcriptional-profiles-of-follicular-dendritic-cell-sarcomas
#7
Maria Antonella Laginestra, Claudio Tripodo, Claudio Agostinelli, Giovanna Motta, Sylvia Hartmann, Claudia Doring, Maura Rossi, Federica Melle, Maria Rosaria Sapienza, Valentina Tabanelli, Alessandro Pileri, Fabio Fuligni, Anna Gazzola, Claudia Mannu, Carlo Alberto Sagramoso, Silvia Lonardi, Luisa Lorenzi, Francesco Bacci, Elena Sabattini, Anita Borges, Ingrid Simonitsch-Klupp, Jose Cabecadas, Elias Campo, Juan Rosai, Martin-Leo Hansmann, Fabio Facchetti, Stefano Aldo Pileri
: Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumors (MTs) with variable clinical, morphologic and phenotypic characteristics. Transcriptome analysis was performed on multiple FDC sarcomas and compared to other MTs, microdissected Castleman FDCs, and normal fibroblasts. Using unsupervised analysis, FDC sarcomas clustered with microdissected FDCs, distinct from other MTs and fibroblasts. The specific endowment of FDC-related gene expression programs in FDC sarcomas emerged by applying a gene signature of differentially expressed genes (n=1,289) between microdissected FDCs and fibroblasts...
January 27, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28122135/pd-1-expression-correlates-with-disease-severity-and-il-5-in-chronic-rhinosinusitis-with-nasal-polyps
#8
Inge Kortekaas Krohn, Sonja Bobic, James Dooley, Feng Lan, Nan Zhang, Claus Bachert, Brecht Steelant, Dominique Bullens, Adrian Liston, Jan L Ceuppens, Sven F Seys, Peter W Hellings
BACKGROUND: Programmed cell Death 1 (PD-1) is a negative regulator of T cell responses. Expression of PD-1 and its ligands PD-L1 and PD-L2 in chronic rhinosinusitis with nasal polyps (CRSwNP) is poorly studied. METHODS: Expression of PD-1, PD-L1, PD-L2, TGF-β, IL-5 and IL-10 mRNA was measured by RT-PCR on tissue homogenates of patients with CRSwNP (n=21) and healthy controls (n=21) and on primary epithelial cells. Disease severity was scored using the Lund-Mackay scores of maxillo-facial CT scans...
January 25, 2017: Allergy
https://www.readbyqxmd.com/read/28112728/integrated-genomic-and-molecular-characterization-of-cervical-cancer
#9
(no author information available yet)
Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, the largest comprehensive genomic study of cervical cancer to date. We observed striking APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A, and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered novel amplifications in immune targets CD274/PD-L1 and PDCD1LG2/PD-L2, and the BCAR4 lncRNA that has been associated with response to lapatinib...
January 23, 2017: Nature
https://www.readbyqxmd.com/read/28111039/-current-events-in-immunotherapy-for-upper-aerodigestive-tract-cancer
#10
Sophie Outh-Gauer, Christophe Le Tourneau, Chloé Broudin, Florian Scotte, Hélène Roussel, Stéphane Hans, Marion Mandavit, Eric Tartour, Cécile Badoual
Head and neck (HN) carcinomas (mostly represented by squamous cell carcinomas [SCC]) still have a poor prognosis, which could be dramatically improved with immunotherapy. Tumor's microenvironment changes, caused by many endogenous or exogenous events, can correlate with prognosis and therapeutic response. Here, we review recent data regarding HNSCC, nasopharyngeal carcinomas (NPC) and salivary gland malignant tumors, all three being potential target of immunotherapies. About half of HNSCC exhibit PD-L1 expression, this expression being upregulated in HPV-positive tumors...
February 2017: Annales de Pathologie
https://www.readbyqxmd.com/read/28107571/increased-pd-l1-expression-in-breast-and-colon-cancer-stem-cells
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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