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Oncoimmunology

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https://www.readbyqxmd.com/read/29721396/m7824-a-novel-bifunctional-anti-pd-l1-tgf%C3%AE-trap-fusion-protein-promotes-anti-tumor-efficacy-as-monotherapy-and-in-combination-with-vaccine
#1
Karin M Knudson, Kristin C Hicks, Xiaoling Luo, Jin-Qiu Chen, Jeffrey Schlom, Sofia R Gameiro
Tumors evade host immune surveillance through multiple mechanisms, including the generation of a tumor microenvironment that suppresses immune effector function. Secretion of TGFβ and upregulation of immune checkpoint programmed cell death ligand-1 (PD-L1) are two main contributors to immune evasion and tumor progression. Here, we examined the efficacy of a first-in-class bifunctional checkpoint inhibitor, the fusion protein M7824, comprising the extracellular domain of human TGFβRII (TGFβ Trap) linked to the C-terminus of human anti-PD-L1 heavy chain (αPD-L1)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721395/super-charged-nk-cells-inhibit-growth-and-progression-of-stem-like-poorly-differentiated-oral-tumors-in-vivo-in-humanized-blt-mice-effect-on-tumor-differentiation-and-response-to-chemotherapeutic-drugs
#2
Kawaljit Kaur, Paytsar Topchyan, Anna Karolina Kozlowska, Nick Ohanian, Jessica Chiang, Phyu Ou Maung, So-Hyun Park, Meng-Wei Ko, Changge Fang, Ichiro Nishimura, Anahid Jewett
Therapeutic role of NK cells in solid tumors was challenged previously even though their role in hematological malignancies has clearly been established. Furthermore, functions and numbers of NK cells are greatly suppressed in oral cancer patients necessitating effective future NK immunotherapeutic strategies to aid in the control of disease. The humanized-BLT (hu-BLT) mice were used to implant stem-like/undifferentiated oral tumors to study the role of super-charged NK cells with and without feeding with AJ2 probiotic bacteria...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721394/merkel-cell-carcinoma-expresses-the-immunoregulatory-ligand-cd200-and-induces-immunosuppressive-macrophages-and-regulatory-t-cells
#3
Maria Rita Gaiser, Cleo-Aron Weis, Timo Gaiser, Hong Jiang, Kristina Buder-Bakhaya, Esther Herpel, Arne Warth, Ying Xiao, Lingling Miao, Isaac Brownell
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that responds to PD-1/PD-L1 immune checkpoint inhibitors. CD200 is another checkpoint modulator whose receptor is found on tumor-promoting myeloid cells, including M2 macrophages. We found high CD200 mRNA expression in MCC tumors, and CD200 immunostaining was demonstrated on 95.5% of MCC tumors. CD200R-expressing myeloid cells were present in the MCC tumor microenvironment. MCC-associated macrophages had a higher average CD163:CD68 staining ratio (2...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721393/immune-heterogeneity-and-clinicopathologic-characterization-of-igfbp2-in-2447-glioma-samples
#4
Jinquan Cai, Qun Chen, Yuqiong Cui, Jiawei Dong, Meng Chen, Pengfei Wu, Chuanlu Jiang
Glioblastoma is an immunosuppressive, deadly brain tumor. IGFBP2, a circulating biomarker for cancer diagnosis and a potential immunotherapeutic target, is attracting more and more attention from oncologists and clinicians. Thus, it is urgent to thoroughly investigate the immune biological process of IGFBP2 to understand tumor immune complexity and provide potential evidence for anti-IGFBP2 therapy. Through authoritative public databases, we enrolled a total of 2447 glioma samples with gene expression profiles...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721392/bufalin-suppresses-migration-and-invasion-of-hepatocellular-carcinoma-cells-elicited-by-poly-i-c-therapy
#5
Yinglu Feng, Yongan Chen, Yongbin Meng, Qingxin Cao, Qun Liu, Changquan Ling, Chen Wang
The Toll-like receptor 3 (TLR3) agonists as polyriboinosinic-polyribocytidylic acid (poly (I:C)) have been implicated as potential immunotherapy adjuvant for cancer whereas the exact roles of TLR3 agonists in hepatocellular carcinoma (HCC) treatment have not been clearly evaluated. In consistent with previous reports, we found that poly (I:C) triggering of TLR3 inhibited cell proliferation and induced apoptosis in HCC cells. However, poly (I:C), when used at lower concentration that cannot remarkably inhibit proliferation and induce apoptosis in HCC cells, enhanced the migration and invasion in vitro and the metastasis in vivo...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721391/a-genetic-ifn-stat1-fas-axis-determines-cd4-t-stem-cell-memory-levels-and-apoptosis-in-healthy-controls-and-adult-t-cell-leukemia-patients
#6
Ricardo Khouri, Gilvanéia Silva-Santos, Tim Dierckx, Soraya Maria Menezes, Daniele Decanine, Kristof Theys, Aline Clara Silva, Lourdes Farré, Achiléa Bittencourt, Massimo Mangino, Mario Roederer, Anne-Mieke Vandamme, Johan Van Weyenbergh
Adult T-cell leukemia (ATL) is an aggressive, chemotherapy-resistant CD4+ CD25+ leukemia caused by HTLV-1 infection, which usually develops in a minority of patients several decades after infection. IFN + AZT combination therapy has shown clinical benefit in ATL, although its mechanism of action remains unclear. We have previously shown that an IFN-responsive FAS promoter polymorphism in a STAT1 binding site (rs1800682) is associated to ATL susceptibility and survival. Recently, CD4 T stem cell memory (TSCM ) Fashi cells have been identified as the hierarchical cellular apex of ATL, but a possible link between FAS, apoptosis, proliferation and IFN response in ATL has not been studied...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721390/cd96-targeted-antibodies-need-not-block-cd96-cd155-interactions-to-promote-nk-cell-anti-metastatic-activity
#7
Amelia Roman Aguilera, Viviana P Lutzky, Deepak Mittal, Xian-Yang Li, Kimberley Stannard, Kazuyoshi Takeda, Günter Bernhardt, Michele W L Teng, William C Dougall, Mark J Smyth
CD96 is a transmembrane glycoprotein Ig superfamily receptor, expressed on various T cell subsets and NK cells, that interacts with nectin and nectin-like proteins, including CD155/polio virus receptor (PVR). Here, we have compared three rat anti-mouse CD96 mAbs, including two that block CD96-CD155 (3.3 and 6A6) and one that does not block CD96-CD155 (8B10). Using flow cytometry, we demonstrated that both mAbs 3.3 and 6A6 bind to the first Ig domain of mouse CD96 and compete with CD155 binding, while mAb 8B10 binds to the second Ig domain and does not block CD155...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721389/bacterial-ghosts-as-adjuvant-to-oxaliplatin-chemotherapy-in-colorectal-carcinomatosis
#8
Diana Groza, Sebastian Gehrig, Pavol Kudela, Martin Holcmann, Christine Pirker, Carina Dinhof, Hemma H Schueffl, Marek Sramko, Julia Hoebart, Fatih Alioglu, Michael Grusch, Manfred Ogris, Werner Lubitz, Bernhard K Keppler, Irena Pashkunova-Martic, Christian R Kowol, Maria Sibilia, Walter Berger, Petra Heffeter
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality worldwide. At late stage of the disease CRC often shows (multiple) metastatic lesions in the peritoneal cavity which cannot be efficiently targeted by systemic chemotherapy. This is one major factor contributing to poor prognosis. Oxaliplatin is one of the most commonly used systemic treatment options for advanced CRC. However, drug resistance - often due to insufficient drug delivery - is still hampering successful treatment...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721388/circulating-tumor-dna-evaluated-by-next-generation-sequencing-is-predictive-of-tumor-response-and-prolonged-clinical-benefit-with-nivolumab-in-advanced-non-small-cell-lung-cancer
#9
Etienne Giroux Leprieur, Guillaume Herbretau, Coraline Dumenil, Catherine Julie, Violaine Giraud, Sylvie Labrune, Jennifer Dumoulin, Julie Tisserand, Jean-François Emile, Hélène Blons, Thierry Chinet
Nivolumab is an anti-PD1 antibody, given in second-line or later treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to describe the predictive value of circulating tumor DNA (ctDNA) on the efficacy of nivolumab in advanced NSCLC. We prospectively included all consecutive patients with advanced NSCLC treated with nivolumab in our Department between June 2015 and October 2016. Plasma samples were obtained before the first injection of nivolumab and at the first tumor evaluation with nivolumab...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721387/development-of-anti-drug-antibodies-is-associated-with-shortened-survival-in-patients-with-metastatic-melanoma-treated-with-ipilimumab
#10
Anders H Kverneland, Christian Enevold, Marco Donia, Lars Bastholt, Inge Marie Svane, Claus H Nielsen
Introduction: Checkpoint inhibitors, including the CTLA-4 blocking antibody ipilimumab, have become the new standard therapy for many metastatic cancers. Development of anti-drug antibodies (ADAs) after treatment with other biopharmaceuticals has been thoroughly described, but the induction of ADAs after treatment with checkpoint inhibitors has been inadequately investigated. In this retrospective study, we relate ipilimumab serum levels and anti-ipilimumab antibody levels to clinical outcomes in patients with metastatic melanoma (MM)...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721386/in-situ-delivery-of-allogeneic-natural-killer-cell-nk-combined-with-cetuximab-in-liver-metastases-of-gastrointestinal-carcinoma-a-phase-i-clinical-trial
#11
O Adotevi, Y Godet, J Galaine, Z Lakkis, I Idirene, J M Certoux, M Jary, R Loyon, C Laheurte, S Kim, A Dormoy, F Pouthier, C Barisien, F Fein, P Tiberghien, X Pivot, S Valmary-Degano, C Ferrand, P Morel, E Delabrousse, C Borg
Despite successful introduction of NK-based cellular therapy in the treatment of myeloid leukemia, the potential use of NK alloreactivity in solid malignancies is still elusive. We performed a phase I clinical trial to assess the safety and efficacy of in situ delivery of allogeneic NK cells combined with cetuximab in liver metastasis of gastrointestinal origin. The conditioning chemotherapy was administrated before the allogeneic NK cells injection via hepatic artery. Three escalating doses were tested (3...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721385/prognosis-of-ovarian-cancer-is-associated-with-effector-memory-cd8-t-cell-accumulation-in-ascites-cxcl9-levels-and-activation-triggered-signal-transduction-in-t-cells
#12
Sonja Lieber, Silke Reinartz, Hartmann Raifer, Florian Finkernagel, Tobias Dreyer, Holger Bronger, Julia M Jansen, Uwe Wagner, Thomas Worzfeld, Rolf Müller, Magdalena Huber
The accumulation of intratumoral CD8+ T cells is associated with the survival of high grade serous ovarian carcinoma patients, but it is unclear which CD8+ T cell subsets contribute to this effect and how they are affected by the peritoneal tumor microenvironment. Here, we provide evidence for a functional link between long relapse-free survival, accumulation of CD8+ effector memory T (TEM ) cells in peritoneal effusion (ascites), and the level of the CD8+ TEM attracting chemokine CXCL9, produced by macrophages as a major source...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721384/low-dose-gemcitabine-increases-the-cytotoxicity-of-human-v%C3%AE-9v%C3%AE-2-t-cells-in-bladder-cancer-cells-in-vitro-and-in-an-orthotopic-xenograft-model
#13
Teruki Shimizu, Mako Tomogane, Masatsugu Miyashita, Osamu Ukimura, Eishi Ashihara
Human γδT cell immunotherapy is well tolerated and has shown promising results in clinical trials; however, its antitumor efficacy is limited, including results in solid tumors. Ex-vivo expanded γδT cell stimulated by zoledronic acid (ZOL) activates the γδT cell subpopulation of so called Vγ9Vδ2 T cells. To improve the clinical outcomes of Vγ9Vδ2 T cell (abbreviated as γδT cell here) immunotherapy, we aimed to increase the cytotoxicity of γδT cells by focusing on two issues: recognition of tumor cells by γδT cells and the effector (γδT cell)-to-target (tumor cell) (E/T) ratio...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721383/myeloid-derived-macrophages-and-secreted-hsp90%C3%AE-induce-pancreatic-ductal-adenocarcinoma-development
#14
Chia-Chi Chen, Li-Li Chen, Chung-Pin Li, Yu-Ting Hsu, Shih-Sheng Jiang, Chi-Shuan Fan, Kee Voon Chua, Sheng-Xiang Huang, Yi-Ming Shyr, Li-Tzong Chen, Tze-Sing Huang
We detected a significant elevation of serum HSP90α levels in pancreatitis patients and even more in pancreatic ductal adenocarcinoma (PDAC) patients. However, there was no significant difference in the serum HSP90α levels between patients with early-stage and late-stage PDAC. To study whether elevation of serum HSP90α levels occurred early during PDAC development, we used LSL-KrasG12D/Pdx1-Cre transgenic mice as a studying model. Elevated serum HSP90α levels were detected before PDAC formation and an extracellular HSP90α (eHSP90α) inhibitor effectively prevented PDAC development...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721382/expression-of-llt1-and-its-receptor-cd161-in-lung-cancer-is-associated-with-better-clinical-outcome
#15
Véronique M Braud, Jérôme Biton, Etienne Becht, Samantha Knockaert, Audrey Mansuet-Lupo, Estelle Cosson, Diane Damotte, Marco Alifano, Pierre Validire, Fabienne Anjuère, Isabelle Cremer, Nicolas Girard, Dominique Gossot, Agathe Seguin-Givelet, Marie-Caroline Dieu-Nosjean, Claire Germain
Co-stimulatory and inhibitory receptors expressed by immune cells in the tumor microenvironment modulate the immune response and cancer progression. Their expression and regulation are still not fully characterized and a better understanding of these mechanisms is needed to improve current immunotherapies. Our previous work has identified a novel ligand/receptor pair, LLT1/CD161, that modulates immune responses. Here, we extensively characterize its expression in non-small cell lung cancer (NSCLC). We show that LLT1 expression is restricted to germinal center (GC) B cells within tertiary lymphoid structures (TLS), representing a new hallmark of the presence of active TLS in the tumor microenvironment...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721381/foxo1-promotes-resistance-of-non-hodgkin-lymphomas-to-anti-cd20-based-therapy
#16
Beata Pyrzynska, Michal Dwojak, Abdessamad Zerrouqi, Giulia Morlino, Piotr Zapala, Nina Miazek, Agnieszka Zagozdzon, Kamil Bojarczuk, Malgorzata Bobrowicz, Marta Siernicka, Marcin M Machnicki, Stefania Gobessi, Joanna Barankiewicz, Ewa Lech-Maranda, Dimitar G Efremov, Przemyslaw Juszczynski, Dinis Calado, Jakub Golab, Magdalena Winiarska
Diminished overall survival rate of non-Hodgkin lymphoma (NHL) patients treated with a combination regimen of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) has been recently linked to recurrent somatic mutations activating FOXO1. Despite of the clinical relevance of this finding, the molecular mechanism driving resistance to R-CHOP therapy remains largely unknown. Herein, we investigated the potential role of FOXO1 in the therapeutic efficacy of rituximab, the only targeted therapy included in the R-CHOP regimen...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721380/targeted-overexpression-of-prostacyclin-synthase-inhibits-lung-tumor-progression-by-recruiting-cd4-t-lymphocytes-in-tumors-that-express-mhc-class-ii
#17
Howard Y Li, Maria McSharry, Deandra Walker, Amber Johnson, Jeff Kwak, Bonnie Bullock, Alexander Neuwelt, Joanna M Poczobutt, Trisha R Sippel, Robert L Keith, Mary C M Weiser-Evans, Eric Clambey, Raphael A Nemenoff
Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We investigated the effects of pulmonary PGIS overexpression in an orthotopic immunocompetent mouse model of lung cancer using two murine lung cancer cell lines. Pulmonary PGIS overexpression significantly inhibited CMT167 lung tumor growth, increased CXCL9 expression, and increased CD4+ tumor-infiltrating lymphocytes...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721379/increased-immune-infiltration-and-chemokine-receptor-expression-in-head-and-neck-epithelial-tumors-after-neoadjuvant-immunotherapy-with-the-irx-2-regimen
#18
Neil L Berinstein, Michael McNamara, Ariane Nguyen, James Egan, Gregory T Wolf
IRX-2 is an injectable cancer immunotherapy composed of cytokines purified from stimulated normal-donor peripheral blood mononuclear cells. In a phase 2a trial (n = 27), neoadjuvant IRX-2 significantly increased lymphocyte infiltration (LI) into resected head and neck tumors and was associated with changes in fibrosis and necrosis. Event-free survival was 65% at 2 years, and overall survival 65% at 5 years. Overall survival was longer for patients with LI greater versus lower than the median. This substudy of the mechanisms responsible for the increase in LI with neoadjuvant IRX-2 employed multiplex immunohistochemistry (IHC) and transcriptome analysis to interrogate matched pre- and post-treatment tumor specimens from 7 available phase 2a trial patients...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721378/a-phase-ii-study-of-combined-therapy-with-a-braf-inhibitor-vemurafenib-and-interleukin-2-aldesleukin-in-patients-with-metastatic-melanoma
#19
Meghan J Mooradian, Alexandre Reuben, Peter A Prieto, Mehlika Hazar-Rethinam, Dennie T Frederick, Brandon Nadres, Adriano Piris, Vikram Juneja, Zachary A Cooper, Arlene H Sharpe, Ryan B Corcoran, Keith T Flaherty, Donald P Lawrence, Jennifer A Wargo, Ryan J Sullivan
Background : Approximately 50% of melanomas harbor BRAF mutations. Treatment with BRAF +/- MEK inhibition is associated with favorable changes in the tumor microenvironment thus providing the rationale for combining targeted agents with immunotherapy. Methods : Patients with unresectable Stage III or IV BRAFV600E mutant melanoma were enrolled in a single-center prospective study (n = 6). Patients were eligible to receive two courses of HD-IL-2 and vemurafenib twice daily. The primary endpoint was progression-free survival (PFS) with secondary objectives including overall survival (OS), response rates (RR), and safety of combination therapy as compared to historical controls...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721377/oncolytic-influenza-virus-infection-restores-immunocompetence-of-lung-tumor-associated-alveolar-macrophages
#20
Dörthe Masemann, Katharina Köther, Meike Kuhlencord, Georg Varga, Johannes Roth, Brian Dennis Lichty, Ulf Rüdiger Rapp, Viktor Wixler, Stephan Ludwig
Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and demonstrates high resistance to radiation and chemotherapy. These tumors evade immune system detection by promoting an immunosuppressive tumor microenvironment. Genetic analysis has revealed oncogenic activation of the Ras/Raf/MEK/ERK signaling pathway to be a hallmark of NSCLCs, which promotes influenza A virus (IAV) infection and replication in these cells. Thus, we aimed to unravel the oncolytic properties of IAV infection against NSCLCs in an immunocompetent model in vivo ...
2018: Oncoimmunology
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