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Pancreatic cancer,CD4,CD8

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https://www.readbyqxmd.com/read/30426614/t-cell-receptor-%C3%AE-chain-repertoire-analysis-of-tumor-infiltrating-lymphocytes-in-pancreatic-cancer
#1
Can Cui, Xiuyun Tian, Jianhui Wu, Chaoting Zhang, Qin Tan, Xiaoya Guan, Bin Dong, Min Zhao, Zheming Lu, Chunyi Hao
Pancreatic cancer is lethal due to lack of perceptible symptoms and effective treatment methods. Immunotherapy may provide promising therapeutic choices for malignant tumors like pancreatic cancer. Tumor infiltrating lymphocytes (TILs) in tumor mesenchyme could recognize peptide antigens presented on the surface of tumor cells. This study aimed to test the relationship between the TCR β repertoire of the tumor and peripheral blood, and also to investigate the intra-tumor spatial heterogeneity of the TCR β repertoire in pancreatic cancer...
November 13, 2018: Cancer Science
https://www.readbyqxmd.com/read/30424804/targeting-myeloid-inflamed-tumor-with-anti-csf-1r-antibody-expands-cd137-effector-t-cells-in-the-murine-model-of-pancreatic-cancer
#2
May Tun Saung, Stephen Muth, Ding Ding, Dwayne L Thomas, Alex B Blair, Takahiro Tsujikawa, Lisa Coussens, Elizabeth M Jaffee, Lei Zheng
BACKGROUND: The pancreatic cancer vaccine, GVAX, induces novel lymphoid aggregates in the otherwise immune quiescent pancreatic ductal adenocarcinoma (PDAC). GVAX also upregulates the PD-1/PD-L1 pathway, and a pre-clinical model demonstrated the anti-tumor effects of combination GVAX and anti-PD-1 antibody therapy (GVAX/αPD-1). Resistance to GVAX was associated with an immune-suppressive myeloid cell infiltration, which may limit further therapeutic gains of GVAX/αPD-1 therapy. The expression of CSF-1R, a receptor important for myeloid cell migration, differentiation and survival, and the effect of its therapeutic blockade in the context of GVAX in PDAC has not been investigated...
November 13, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/30325778/increased-risk-of-anal-squamous-cell-carcinoma-in-hiv-positive-men-with-prior-hepatitis-b-virus-infection
#3
Jordan Aldersley, David R Lorenz, Vikas Misra, Hajime Uno, Dana Gabuzda
OBJECTIVE(S): HIV-positive individuals have elevated rates of anal squamous cell carcinoma (SCC), and sexually transmitted infections with its causative agent, high-risk human papillomavirus, and other oncoviruses including hepatitis B virus (HBV). HBV infection can cause liver cancer, and has been associated with increased risk of some extra-hepatic cancers including biliary tract cancer, pancreatic cancer, and non-Hodgkin lymphoma. Whether HBV is associated with anal SCC risk is unknown...
January 27, 2019: AIDS
https://www.readbyqxmd.com/read/30214445/pd1-cd28-fusion-protein-enables-cd4-t-cell-help-for-adoptive-t-cell-therapy-in-models-of-pancreatic-cancer-and-non-hodgkin-lymphoma
#4
Felicitas Rataj, Fabian B T Kraus, Michael Chaloupka, Simon Grassmann, Constanze Heise, Bruno L Cadilha, Peter Duewell, Stefan Endres, Sebastian Kobold
Background: Interaction of the programmed death receptor 1 (PD-1) and its ligand, PD-L1, suppresses T cell activity and permits tumors to evade T cell-mediated immune surveillance. We have recently demonstrated that antigen-specific CD8+ T cells transduced with a PD1-CD28 fusion protein are protected from PD-1-mediated inhibition. We have now investigated the potential of PD1-CD28 fusion protein-transduced CD4+ T cells alone or in combination with CD8+ T cells for immunotherapy of pancreatic cancer and non-Hodgkin lymphoma...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30135623/neutralizing-tgf-%C3%AE-promotes-anti-tumor-immunity-of-dendritic-cells-against-pancreatic-cancer-by-regulating-t-lymphocytes
#5
Ning Pu, Guochao Zhao, Shanshan Gao, Yutong Cui, Yadong Xu, Yang Lv, Abulimiti Nuerxiati, Wenchuan Wu
Previous fundamental or clinical trials of dendritic cell (DC) vaccine against pancreatic ductal adenocarcinoma (PDAC) revealed the burgeoning neoadjuvant immunotherapy. Microarray studies indicated that multiple ingredients of the transfer growth factor beta (TGF-β) pathway were overexpressed in PDAC, which inhibited the intratumoral immune response. To explore whether the DC volume in tumor microenvironment contributes to the differentiation of T cell cohort and test the hypothesis that combining DC vaccine with TGF-β inhibitors will elevate the anti-tumor immune response, we managed to co-culture T cells in vitro with pancreatic cancer cells and DCs in different concentrations, and combine TGF-β blockage with DC vaccine therapy in a murine model of pancreatic cancer...
2018: Central-European Journal of Immunology
https://www.readbyqxmd.com/read/30092175/immune-cell-and-stromal-signature-associated-with-progression-free-survival-of-patients-with-resected-pancreatic-ductal-adenocarcinoma
#6
Ujjwal Mukund Mahajan, Eno Langhoff, Elisabetta Goni, Eithne Costello, William Greenhalf, Christopher Halloran, Steffen Ormanns, Stephan Kruger, Stefan Boeck, Silvia Ribback, Georg Beyer, Frank Dombroswki, Frank-Ulrich Weiss, John P Neoptolemos, Jens Werner, Jan G D'Haese, Alexandr Bazhin, Julian Peterhansl, Svenja Pichlmeier, Markus W Büchler, Jörg Kleeff, Paula Ganeh, Matthias Sendler, Daniel H Palmer, Thomas Kohlmann, Roland Rad, Ivonne Regel, Markus M Lerch, Julia Mayerle
BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils...
November 2018: Gastroenterology
https://www.readbyqxmd.com/read/30021156/the-ubiquitin-ligase-adaptor-ndfip1-selectively-enforces-a-cd8-t-cell-tolerance-checkpoint-to-high-dose-antigen
#7
Mayura V Wagle, Julia M Marchingo, Jason Howitt, Seong-Seng Tan, Christopher C Goodnow, Ian A Parish
Escape from peripheral tolerance checkpoints that control cytotoxic CD8+ T cells is important for cancer immunotherapy and autoimmunity, but pathways enforcing these checkpoints are mostly uncharted. We reveal that the HECT-type ubiquitin ligase activator, NDFIP1, enforces a cell-intrinsic CD8+ T cell checkpoint that desensitizes TCR signaling during in vivo exposure to high antigen levels. Ndfip1-deficient OT-I CD8+ T cells responding to high exogenous tolerogenic antigen doses that normally induce anergy aberrantly expanded and differentiated into effector cells that could precipitate autoimmune diabetes in RIP-OVAhi mice...
July 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29980536/il35-hinders-endogenous-antitumor-t-cell-immunity-and-responsiveness-to-immunotherapy-in-pancreatic-cancer
#8
Bhalchandra Mirlekar, Daniel Michaud, Ryan Searcy, Kevin Greene, Yuliya Pylayeva-Gupta
Although successes in cancer immunotherapy have generated considerable excitement, this form of treatment has been largely ineffective in patients with pancreatic ductal adenocarcinoma (PDA). Mechanisms that contribute to the poor antitumor immune response in PDA are not well understood. Here, we demonstrated that cytokine IL35 is a major immunosuppressive driver in PDA and potentiates tumor growth via the suppression of endogenous antitumor T-cell responses. The growth of pancreatic tumors in mice deficient for IL35 was significantly reduced...
September 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29958796/cyclophosphamide-with-or-without-fluorouracil-followed-by-subcutaneous-or-intravenous-interleukin-2-use-in-solid-tumors-a-feasibility-off-label-experience
#9
Giovanni Lo Re, Francesco Lo Re, Paolo Doretto, Alessandro Del Conte, Maria Amadio, Cinzia Cozzi, Maria Maddalena Casarotto, Daniele Maruzzi, Wally Marus, Paolo Ubiali, Paolo Sandri
BACKGROUND: Immune tolerance seems to correlate with disease progression and T regulatory cells (Tregs) and myeloid-derived suppressor cells play a relevant role in immunosuppression. Cyclophosphamide (Cyt) and Fluorouracil (FU) seem to reduce these cell populations. METHODS AND OBJECTIVE: Establishing safety, feasibility, activity and impact on the immune system (neutrophil/lymphocyte [N/L], platelet/L [Plt/L], monocyte [M] and lymphocyte subpopulation (CD3, CD4, CD8, CD16, HLADR/CD3, Tregs, cells count), CD8/Treg and C-reactive protein (CRP)...
June 26, 2018: Cytokine
https://www.readbyqxmd.com/read/29889816/murine-pancreatic-cancer-alters-t-cell-activation-and-apoptosis-and-worsens-survival-after-cecal-ligation-and-puncture
#10
John D Lyons, Ching-Wen Chen, Zhe Liang, Wenxiao Zhang, Deena B Chihade, Eileen M Burd, Alton B Farris, Mandy L Ford, Craig M Coopersmith
Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. However, pancreatic cancer/pneumonia decreases lymphocyte apoptosis and increases gut apoptosis while lung cancer/CLP increases lymphocyte apoptosis and decreases intestinal proliferation...
June 20, 2018: Shock
https://www.readbyqxmd.com/read/29661773/integrated-genomic-and-immunophenotypic-classification-of-pancreatic-cancer-reveals-three-distinct-subtypes-with-prognostic-predictive-significance
#11
Martin Wartenberg, Silvia Cibin, Inti Zlobec, Erik Vassella, Serenella Eppenberger-Castori, Luigi Terracciano, Micha David Eichmann, Mathias Worni, Beat Gloor, Aurel Perren, Eva Karamitopoulou
Purpose: Current clinical classification of pancreatic ductal adenocarcinoma (PDAC) is unable to predict prognosis or response to chemo- or immunotherapy and does not take into account the host reaction to PDAC cells. Our aim is to classify PDAC according to host- and tumor-related factors into clinically/biologically relevant subtypes by integrating molecular and microenvironmental findings. Experimental Design: A well-characterized PDAC cohort ( n = 110) underwent next-generation sequencing with a hot spot cancer panel while next-generation tissue microarrays were immunostained for CD3, CD4, CD8, CD20, PD-L1, p63, hyaluronan-mediated motility receptor (RHAMM), and DNA mismatch repair proteins...
September 15, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29567829/the-pancreatic-cancer-microbiome-promotes-oncogenesis-by-induction-of-innate-and-adaptive-immune-suppression
#12
Smruti Pushalkar, Mautin Hundeyin, Donnele Daley, Constantinos P Zambirinis, Emma Kurz, Ankita Mishra, Navyatha Mohan, Berk Aykut, Mykhaylo Usyk, Luisana E Torres, Gregor Werba, Kevin Zhang, Yuqi Guo, Qianhao Li, Neha Akkad, Sarah Lall, Benjamin Wadowski, Johana Gutierrez, Juan Andres Kochen Rossi, Jeremy W Herzog, Brian Diskin, Alejandro Torres-Hernandez, Josh Leinwand, Wei Wang, Pardeep S Taunk, Shivraj Savadkar, Malvin Janal, Anjana Saxena, Xin Li, Deirdre Cohen, R Balfour Sartor, Deepak Saxena, George Miller
We found that the cancerous pancreas harbors a markedly more abundant microbiome compared with normal pancreas in both mice and humans, and select bacteria are differentially increased in the tumorous pancreas compared with gut. Ablation of the microbiome protects against preinvasive and invasive pancreatic ductal adenocarcinoma (PDA), whereas transfer of bacteria from PDA-bearing hosts, but not controls, reverses tumor protection. Bacterial ablation was associated with immunogenic reprogramming of the PDA tumor microenvironment, including a reduction in myeloid-derived suppressor cells and an increase in M1 macrophage differentiation, promoting TH1 differentiation of CD4+ T cells and CD8+ T-cell activation...
April 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29037917/immunomodulation-after-radiofrequency-ablation-of-locally-advanced-pancreatic-cancer-by-monitoring-the-immune-response-in-10-patients
#13
Alessandro Giardino, Giulio Innamorati, Stefano Ugel, Omar Perbellini, Roberto Girelli, Isabella Frigerio, Paolo Regi, Filippo Scopelliti, Giovanni Butturini, Salvatore Paiella, Matilde Bacchion, Claudio Bassi
OBJECTIVE/BACKGROUND: RFA of pancreatic cancer has been demonstrated to be feasible and safe with a positive impact on survival. The aim was to investigate whether an immune reaction is activated after locally advanced pancreatic cancer (LAPC) ablation. METHODS: Peripheral Blood samples were obtained preoperatively and on post-operative days 3-30. Evaluated parameters were: cells [CD4+ , CD8+ and activated subsets, T-Reg, Monocytes, myeloid and plasmocytoid Dendritic cells (mDC and pDC)] and cytokines [Interleukin (IL)-6, Stromal-cells derived factor (SDF)-1, IL-1β, Tumour-Necrosis Factor (TNF)-α, Interferon (IFN)-γ, Vascular Endothelial Growth Factor (VEGF), chemokine (C-C motif) ligand 5 (CCL-5), Transforming-Growth Factor (TGF)-β]...
November 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28942020/cd25-expressing-th17-cells-mediate-cd8-t-cell-suppression-in-ctla-4-dependent-mechanisms-in-pancreatic-ductal-adenocarcinoma
#14
Cuicui Lang, Jinyan Wang, Lei Chen
The tumor-associated immune response is governed by the signalling events of various regulatory molecules, one of which is the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4). In conventional T cells, CTLA-4 could outcompete CD28 in binding to CD80/86 but does not produce a co-stimulatory signal, resulting in T cell anergy. CTLA-4 in regulatory T cells (Tregs) could also function in a cell-extrinsic fashion by removing CD80/CD86 from the antigen-presenting cells (APCs), thus preventing further priming of other T cells...
November 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28856392/ctla-4-cd80-pathway-regulates-t-cell-infiltration-into-pancreatic-cancer
#15
Fee Bengsch, Dawson M Knoblock, Anni Liu, Florencia McAllister, Gregory L Beatty
The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. We hypothesized that CTLA-4 blockade, despite a lack of clinical efficacy seen thus far in PDAC, might still alter T cell immunobiology, which would have therapeutic implications...
December 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28802662/the-metastasis-status-and-tumor-burden-associated-ca125-level-combined-with-the-cd4-cd8-ratio-predicts-the-prognosis-of-patients-with-advanced-pancreatic-cancer-a-new-scoring-system
#16
C Yang, H Cheng, G Luo, Y Lu, M Guo, K Jin, Z Wang, X Yu, C Liu
INTRODUCTION: Although CA125 and the tumor immune response have been reported to be associated with pancreatic cancer, their prognostic value for advanced pancreatic cancer patients undergoing chemotherapy remain uncertain. We thus studied the prognostic value of the combination of the CA125 level with the CD4/CD8 ratio. METHODS: After excluding patients who were lost to follow-up or for whom complete clinical data were missing, 369 participants were ultimately examined...
November 2017: European Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28798308/prognostic-value-of-programmed-cell-death-protein-1-expression-on-cd8-t-lymphocytes-in-pancreatic-cancer
#17
Tao Shen, Liangjing Zhou, Hua Shen, Chengfei Shi, Shengnan Jia, Guo Ping Ding, Liping Cao
Pancreatic cancer is one of the most aggressive malignancies and has a highly immunosuppressive tumour microenvironment. Immune checkpoint blockade has led to remarkable and durable objective responses in a number of malignancies and antibody-based strategies targeting programmed cell death protein 1 (PD-1) are showing promise where traditional modalities of surgery, radiotherapy, and chemotherapy have failed. In this study, we examined the clinical value of PD-1 protein expression by CD8+ peripheral T lymphocytes or tumour-infiltrating T lymphocytes (TILs) in pancreatic ductal adenocarcinoma (PDAC)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770166/genomic-signature-of-the-natural-oncolytic-herpes-simplex-virus-hf10-and-its-therapeutic-role-in-preclinical-and-clinical-trials
#18
REVIEW
Ibrahim Ragab Eissa, Yoshinori Naoe, Itzel Bustos-Villalobos, Toru Ichinose, Maki Tanaka, Wu Zhiwen, Nobuaki Mukoyama, Taishi Morimoto, Noriyuki Miyajima, Hasegawa Hitoki, Seiji Sumigama, Branko Aleksic, Yasuhiro Kodera, Hideki Kasuya
Oncolytic viruses (OVs) are opening new possibilities in cancer therapy with their unique mechanism of selective replication within tumor cells and triggering of antitumor immune responses. HF10 is an oncolytic herpes simplex virus-1 with a unique genomic structure that has non-engineered deletions and insertions accompanied by frame-shift mutations, in contrast to the majority of engineered OVs. At the genetic level, HF10 naturally lacks the expression of UL43, UL49.5, UL55, UL56, and latency-associated transcripts, and overexpresses UL53 and UL54...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28714519/circulating-regulatory-t-cell-subsets-predict-overall-survival-of-patients-with-unresectable-pancreatic-cancer
#19
Chen Liu, He Cheng, Guopei Luo, Yu Lu, Kaizhou Jin, Meng Guo, Quanxing Ni, Xianjun Yu
Most patients with pancreatic ductal adenocarcinoma (PDAC) have unresectable cancers with a dismal prognosis, in which cohort chemotherapy is the primary treatment. T cell immune adaption is critical for tumor immune escape and prognosis of this disease. The present study aimed to determine the correlation between peripheral T cell subset distribution in patients with unresectable PDAC and their response to chemotherapy. Two hundred and twelve patients with unresectable PDAC were included whose blood samples were collected for analysis of T cell subsets, including CD3+, CD4+, CD8+, CD8+CD28+ and CD4+CD25+CD127 T cells by flow cytometry before and after gemcitabine-based chemotherapy...
August 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28611200/dendritic-cell-cytokine-induced-killer-cell-immunotherapy-combined-with-s-1-in-patients-with-advanced-pancreatic-cancer-a-prospective-study
#20
Ni Jiang, Guoliang Qiao, Xiaoli Wang, Michael A Morse, William R Gwin, Lei Zhou, Yuguang Song, Yanjie Zhao, Feng Chen, Xinna Zhou, Lefu Huang, Amy Hobeika, Xin Yi, Xuefeng Xia, Yanfang Guan, Jin Song, Jun Ren, H Kim Lyerly
Purpose: Advanced pancreatic cancer has remained challenging to treat effectively. This study aimed to investigate the clinical effects and safety of immunotherapy with dendritic cells and cytokine-induced killer cells (DC-CIK) administered with the chemotherapy (CT) S-1 in this malignancy. Experimental Design: Consecutive patients ( n = 47) with advanced pancreatic cancer were treated with either DC-CIK + S-1, DC-CIK alone, S-1 alone, or best supportive care. Results: DC-CIK plus S-1 produced significantly longer median OS and PFS (212 and 136 days) compared with DC-CIK (128 and 85 days), CT (141 and 92 days), or supportive care only (52 and 43 days; P < 0...
September 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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