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https://www.readbyqxmd.com/read/29774031/il-10-producing-b-cells-ability-to-induce-regulatory-t-cells-is-maintained-in-rheumatoid-arthritis
#1
Julie Mielle, Rachel Audo, Michael Hahne, Laurence Macia, Bernard Combe, Jacques Morel, Claire Daien
Despite growing evidence highlighting the relevance of increasing IL-10-producing B cells (B10+ cells) in autoimmune diseases, their functions in patients are still unknown. The aim of this study was to evaluate the functions of CpG-induced B10+ cells isolated from healthy controls (HC) and rheumatoid arthritis (RA) patients, on naïve T cell differentiation. We demonstrated that CpG-induced B10+ cells from HC drove naïve T cell differentiation toward regulatory T cells (Treg cells) and IL-10-producing T cells (Tr1) through IL-10 secretion and cellular contacts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29745928/cancer-immunotherapy-and-the-pd-1-pd-l1-checkpoint-pathway
#2
Jonathan Barclay, Joanne Creswell, Juan León
Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient' immune response by acting on the checkpoints of immune cells...
May 2018: Archivos Españoles de Urología
https://www.readbyqxmd.com/read/29721376/pd-l1-expression-is-regulated-by-both-dna-methylation-and-nf-kb-during-emt-signaling-in-non-small-cell-lung-carcinoma
#3
A Asgarova, K Asgarov, Y Godet, P Peixoto, A Nadaradjane, M Boyer-Guittaut, J Galaine, D Guenat, V Mougey, J Perrard, J R Pallandre, A Bouard, J Balland, C Tirole, O Adotevi, E Hendrick, M Herfs, P F Cartron, C Borg, E Hervouet
Tumor cells, which undergo Epithelial-mesenchymal transition (EMT) acquire increased capacities of proliferation, invasion and have the ability to generate metastases by escaping the immune system during their systemic migration. To escape the immune system, cancer cells may induce tolerance or resist elimination by immune effectors via multiple mechanisms and we hypothesized that EMT may control the expression of immune checkpoint inhibitors, then promoting immune evasion. PD-L1 (programmed cell death ligand 1) but not PD-L2 nor Galectin 9 or Death receptor (DR4, DR5 and Fas) and ligands (FasL and TRAIL) expression was up-regulated during cytokine-driven EMT in a reversible manner...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721184/correlation-between-lower-balance-of-th2-helper-t-cells-and-expression-of-pd-l1-pd-1-axis-genes-enables-prognostic-prediction-in-patients-with-glioblastoma
#4
Yasuo Takashima, Atsushi Kawaguchi, Tomohiko Kanayama, Azusa Hayano, Ryuya Yamanaka
Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 ( PD-L1 ), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 ( PD-1 ), PDCD1LG2 ( PD-L2 ), and TBX21 ( T-bet ) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719073/the-expression-of-programed-death-ligand-1-could-be-related-with-unfavorable-prognosis-in-salivary-duct-carcinoma
#5
Fumihiko Sato, Jun Akiba, Akihiko Kawahara, Yoshiki Naito, Takeharu Ono, Yorihiko Takase, Kazuya Murata, Hideyuki Abe, Tomohiko Yamaguchi, Hiroaki Miyoshi, Yushi Abe, Yutaro Mihara, Masahiko Tanikawa, Momoko Akashi, Hirofumi Kurose, Hirohito Umeno, Hirohisa Yano
BACKGROUND: Salivary duct carcinoma (SDC) is a rare tumor occurring in the salivary gland. SDC is a highly aggressive tumor and its prognosis is extremely poor. Effective treatments in advanced SDC have not yet been established. Recently, immune checkpoint inhibitors have paved the way for the treatment of various malignancies. We examined the expressions of programed death ligand (PD-L) 1/PD-L2 and programed death (PD-1), and the correlation of clinicopathological findings. METHODS: We examined 18 cases of SDC and conducted immunohistochemical staining using formalin-fixed paraffin-embedded full-face sections...
May 2, 2018: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/29715119/eribulin-promotes-antitumor-immune-responses-in-patients-with-locally-advanced-or-metastatic-breast-cancer
#6
Wataru Goto, Shinichiro Kashiwagi, Yuka Asano, Koji Takada, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND/AIM: Several proteins involved in immune regulation and the relationship among these, the tumor microenvironment, and clinical outcomes of eribulin treatment were evaluated in advanced or metastatic breast cancer patients. PATIENTS AND METHODS: This retrospective cohort study comprised 52 eribulin-treated locally advanced or metastatic breast cancer patients. Cancer tissue samples were obtained before and after treatment in 10 patients. Immunohistochemistry was performed to determine programmed death (PD)-1, CD8, and forkhead box P3 (FOXP3) expression by stromal tumor-infiltrating lymphocytes, and PD-ligand (L1) and PD-L2 expression by cancer cells...
May 2018: Anticancer Research
https://www.readbyqxmd.com/read/29676849/hoxc10-promotes-proliferation-and-invasion-and-induces-immunosuppressive-gene-expression-in-glioma
#7
Shu Li, Wenhao Zhang, Chao Wu, Hongliang Gao, Jun Yu, Xiaoqiang Wang, Bin Li, Jun Zhong, Wenchaun Zhang, Ping Zhou, Juanhong Shi, Lifeng Wang, Yunxing Gao, Shiting Li, Bangbao Tao
The prognosis for patients with malignant glioma is very poor and thus the identification of new potential therapeutic targets is critically important. In this work, we report a previously unknown role for the homeobox transcription factor HOXC10 in regulating immunosuppressive gene expression in glioma cell lines, as well as their proliferative and invasive capacities. Although HOXC10 expression is dysregulated in several types of tumors, its potential function in glioma was not known. We found that HOXC10 expression was up-regulated in glioma compared to normal tissue, and that HOXC10 expression positively associated with high grading of glioma...
April 20, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29661724/variation-in-nuclear-size-and-pd-l2-positivity-correlate-with-aggressive-chromophobe-renal-cell-carcinoma
#8
Mohamed E Mostafa, Amrou Abdelkader, Naoto Kuroda, Delia Pérez-Montiel, Anjishnu Banerjee, Ondrej Hes, Kenneth A Iczkowski
Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases)...
January 10, 2018: Annals of Diagnostic Pathology
https://www.readbyqxmd.com/read/29661225/lymphocyte-subset-expression-and-serum-concentrations-of-pd-1-pd-l1-in-sepsis-pilot-study
#9
Julie K Wilson, Yuan Zhao, Mervyn Singer, Jo Spencer, Manu Shankar-Hari
BACKGROUND: Sepsis remains a major cause of mortality in critical care, for which specific treatments are lacking. The dysregulated response to infection seen in sepsis includes features of lymphocyte dysfunction and exhaustion, suggesting that immune-stimulatory therapy may improve outcomes in certain patient groups. Monoclonal antibodies targeting checkpoint molecules, such as programmed-death 1 protein (PD-1) and its ligand PD-L1, have shown success in stimulating the immune response in patients with cancer, and are being considered for future sepsis trials...
April 17, 2018: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/29628925/human-endothelial-cells-modulate-cd4-t-cell-populations-and-enhance-regulatory-t-cell-suppressive-capacity
#10
Wen Chean Lim, Michael Olding, Eugene Healy, Timothy M Millar
Endothelial cells (ECs) line the luminal surface of blood vessels and have an active role in the recruitment of leukocytes, including immune cell activation. Regulatory T cells (Tregs) are immune suppressor cells that maintain peripheral tolerance and must interact with the endothelium as they traffic into tissue. We hypothesized that human ECs could modulate Tregs and their suppressor function. Cocultures of CD4+ T cells with human umbilical vein ECs (HUVECs) or dermal microvascular ECs (HDMECs) were conducted and analyzed for activation and proliferation after 72 and 120 h using flow cytometry...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29616115/expression-of-multiple-immune-checkpoint-molecules-on-t-cells-in-malignant-ascites-from-epithelial-ovarian-carcinoma
#11
Yuichi Imai, Kosei Hasegawa, Hirokazu Matsushita, Nao Fujieda, Sho Sato, Etsuko Miyagi, Kazuhiro Kakimi, Keiichi Fujiwara
Expression of immune checkpoint molecules, including programmed cell death protein-1 (PD-1), has been reported on T cells in various types of cancer. However, the expression status of these molecules in the tumor microenvironment of epithelial ovarian cancer (EOC) has not yet been studied. A total of 54 cases of malignant ascites from patients with EOC were analyzed in the present study. The expression of PD-1, lymphocyte-activation gene-3 (LAG-3), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) and B and T lymphocyte attenuator (BTLA) on cluster of differentiation (CD)4+ and CD8+ T cells in malignant EOC ascites were investigated using multicolor flow cytometric analysis...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29615063/prediction-of-treatment-responses-to-neoadjuvant-chemotherapy-in-triple-negative-breast-cancer-by-analysis-of-immune-checkpoint-protein-expression
#12
Yuka Asano, Shinichiro Kashiwagi, Wataru Goto, Koji Takada, Katsuyuki Takahashi, Tamami Morisaki, Hisakazu Fujita, Tsutomu Takashima, Shuhei Tomita, Masahiko Ohsawa, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: "Avoiding immune destruction" has recently been established as one of the hallmarks of cancer. The programmed cell death (PD)-1/programmed cell death-ligand (PD-L) 1 pathway is an important immunosuppression mechanism that allows cancer cells to escape host immunity. The present study investigated how the expressions of these immune checkpoint proteins affected responses to neo-adjuvant chemotherapy (NAC) in breast cancer. METHODS: A total of 177 patients with resectable early-stage breast cancer were treated with NAC...
April 4, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/29599916/pd-l1-expression-and-presence-of-tils-in-small-intestinal-neuroendocrine-tumours
#13
Angela Lamarca, Daisuke Nonaka, Wolfgang Breitwieser, Garry Ashton, Jorge Barriuso, Mairéad G McNamara, Sharzad Moghadam, Jane Rogan, Wasat Mansoor, Richard A Hubner, Christopher Clark, Bipasha Chakrabarty, Juan W Valle
Background: The extent of resistance to immune surveillance in patients with well-differentiated (Wd) (grade 1/2) small-intestinal neuroendocrine tumours (Si-NETs) is unknown. Methods: Patients diagnosed with Wd Si-NETs (excluding appendix, which are considered to have a different biology to other midgut NETs) were eligible. Tumoural programmed death (PD)-ligand(L) 1 (PD-L1)/PD-L2/PD-1 and tumour infiltrating lymphocytes (TILs) [presence and phenotype] were analysed in archival tissue by immunohistochemistry (IHC); reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used for confirmation of IHC results...
March 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29596910/intrinsic-and-extrinsic-regulation-of-pd-l2-expression-in-oncogene-driven-non-small-cell-lung-cancer
#14
Daisuke Shibahara, Kentaro Tanaka, Eiji Iwama, Naoki Kubo, Keiichi Ota, Koichi Azuma, Taishi Harada, Jiro Fujita, Yoichi Nakanishi, Isamu Okamoto
INTRODUCTION: The interaction of programmed cell death-ligand 2 (PD-L2) with programmed cell death-1 (PD-1) is implicated in tumor immune escape. The regulation of PD-L2 expression in tumor cells has remained unclear, however. We here examined intrinsic and extrinsic regulation of PD-L2 expression in non-small cell lung cancer (NSCLC). METHODS: PD-L2 expression was evaluated by reverse transcription and real-time polymerase chain reaction analysis and by flow cytometry...
March 26, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29571084/comprehensive-analysis-of-cancers-of-unknown-primary-for-the-biomarkers-of-response-to-immune-checkpoint-blockade-therapy
#15
Zoran Gatalica, Joanne Xiu, Jeff Swensen, Semir Vranic
BACKGROUND: Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Avoiding immune destruction is a major cancer characteristic and therapies aimed at immune checkpoint blockade are in use for several specific cancer types. A comprehensive survey of predictive biomarkers to immune checkpoint blockade in CUP were explored in this study. METHODS: About 389 cases of CUP were analysed for mutations in 592 genes and 52 gene fusions using a massively parallel DNA sequencing platform (next-generation sequencing [NGS])...
March 20, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/29556566/the-pekin-duck-programmed-death-ligand-2-cdna-cloning-genomic-structure-molecular-characterization-and-expression-analysis
#16
Qingxia Yao, Karl P Fischer, D Lorne Tyrrell, Klaus S Gutfreund
Programmed death-1 (PD-1), upon engagement by its ligands, programmed death ligand-1 (PD-L1) and programmed death ligand-2 (PD-L2), provides signals that attenuate adaptive immune responses. Here we describe the identification of the Pekin duck PD-L2 (duPD-L2) and its gene structure. The duPD-L2 cDNA encodes a 321 amino acid protein that has an amino acid identity of 76% and 35% with chicken and human PD-L2, respectively. Mapping of the duPD-L2 cDNA with duck genomic sequences revealed an exonic structure similar to that of the human P dcd1lg2 gene...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29552320/effectiveness-of-anti-pd-1-pd-l1-antibodies-in-urothelial-carcinoma-patients-with-different-pd-l1-expression-levels-a-meta-analysis
#17
Junqi Liu, Chuanfeng Zhang, Jiegang Hu, Qing Tian, Xin Wang, Hao Gu, Song Zhang, Di Zhao, Ruitai Fan
Background: Urothelial carcinoma ranks the ninth among malignant cancers. We conducted this study to identify which patients could benefit more from the treatment of programmed death-1 (PD-1)/programmed death-ligand1 (PD-L1) inhibitors. Materials and Methods: We performed literature searches, combined data from qualified literature and performed comparative analyses on the effectiveness of anti-PD-1/PD-L1 antibodies in patients with different PD-L1 expression levels...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29547766/immunotherapy-in-head-and-neck-cancers-a-new-challenge-for-immunologists-pathologists-and-clinicians
#18
REVIEW
Sophie Outh-Gauer, Marie Alt, Christophe Le Tourneau, Jérémy Augustin, Chloé Broudin, Cassandre Gasne, Thomas Denize, Haitham Mirghani, Elizabeth Fabre, Madeleine Ménard, Florian Scotte, Eric Tartour, Cécile Badoual
Cancer occurrence can be understood as the result of dysfunctions in immune tumoral microenvironment. Here we review the recent understandings of those microenvironment changes, regarding their causes and prognostic significance in head and neck (HN) carcinoma. We will focus on HN squamous cell cancer (SCC) and nasopharyngeal carcinomas (NPC). Their overall poor prognosis may be improved with immunotherapy in a subset of patients, as supported by current clinical trials. However, finding reliable markers of therapeutic response is crucial for patient selection, due to potential severe adverse reactions and high costs...
April 2018: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29531164/dendritic-cell-pd-l1-limits-autoimmunity-and-follicular-t-cell-differentiation-and-function
#19
Peter T Sage, Frank A Schildberg, Raymond A Sobel, Vijay K Kuchroo, Gordon J Freeman, Arlene H Sharpe
The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29507342/cancer-associated-fibroblasts-induce-antigen-specific-deletion-of-cd8-t-cells-to-protect-tumour-cells
#20
Matthew A Lakins, Ehsan Ghorani, Hafsa Munir, Carla P Martins, Jacqueline D Shields
Tumours have developed strategies to interfere with most steps required for anti-tumour immune responses. Although many populations contribute to anti-tumour responses, tumour-infiltrating cytotoxic T cells dominate, hence, many suppressive strategies act to inhibit these. Tumour-associated T cells are frequently restricted to stromal zones rather than tumour islands, raising the possibility that the tumour microenvironment, where crosstalk between malignant and "normal" stromal cells exists, may be critical for T cell suppression...
March 5, 2018: Nature Communications
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