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Oncoimmunology

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https://www.readbyqxmd.com/read/29416940/tumor-associated-macrophages-remodeling-emt-and-predicting-survival-in-colorectal-carcinoma
#1
Si Li, Fangying Xu, Jing Zhang, Lili Wang, Yang Zheng, Xuesong Wu, Jing Wang, Qiong Huang, Maode Lai
The immune contexture, a composition of the tumor microenvironment, plays multiple important roles in cancer stem cell (CSC) and epithelial-mesenchymal transition (EMT), and hence critically influences tumor initiation, progression and patient outcome. Tumor-associated macrophages (TAMs) are abundant in immune contexture, however their roles in CSC, EMT and prognosis of colorectal cancer (CRC) have not been elucidated. In 419 colorectal carcinomas, immune cell types (CD68+ macrophages, CD3+, CD4+ or CD8+ T lymphocytes, CD20+ B lymphocytes), EMT markers (E-cadherin and Snail) as well as the stem cell marker (CD44v6) were detected in tumor center (TC) and tumor invasive front (TF) respectively by immunohistochemistry...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29416939/maturation-of-tertiary-lymphoid-structures-and-recurrence-of-stage-ii-and-iii-colorectal-cancer
#2
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399416/macrophage-derived-lipocalin-2-transports-iron-in-the-tumor-microenvironment
#3
Christina Mertens, Javier Mora, Bilge Ören, Stephan Grein, Sofia Winslow, Klaus Scholich, Andreas Weigert, Per Malmström, Carina Forsare, Mårten Fernö, Tobias Schmid, Bernhard Brüne, Michaela Jung
While the importance of iron for tumor development is widely appreciated, the exact sources of tumor-supporting iron largely remain elusive. The possibility that iron might be provided by stromal cells in the tumor microenvironment was not taken into account so far. In the present study, we show that tumor-associated macrophages (TAM) acquire an iron-release phenotype upon their interaction with tumor cells, thereby increasing the availability of iron in the tumor microenvironment. Mechanistically, TAM expressed elevated levels of the high-affinity iron-binding protein lipocalin-2 (LCN-2), which appeared to be critical for the export of iron from TAM, and in turn enhanced tumor cell proliferation...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399415/melanoma-induced-immunosuppression-is-mediated-by-hematopoietic-dysregulation
#4
Neha Kamran, Youping Li, Maria Sierra, Mahmoud S Alghamri, Padma Kadiyala, Henry D Appelman, Marta Edwards, Pedro R Lowenstein, Maria G Castro
Tumors are associated with expansion of immunosuppressive cells such as tumor associated macrophages (TAMs), regulatory T cells (Tregs) and myeloid derived suppressor cells (MDSCs). These cells promote tumor growth, angiogenesis, metastasis and immune escape. Cancer patients frequently present symptoms such as anemia, leukocytosis and/or cytopenia; associated with poor prognosis. To uncover tumor-mediated hematopoietic abnormalities and identify novel targets that can be harnessed to improve tumor-specific immune responses, we investigated the hematopoietic stem and progenitor cell compartment in melanoma bearing mice...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399414/virus-like-particle-display-of-her2-induces-potent-anti-cancer-responses
#5
Arianna Palladini, Susan Thrane, Christoph M Janitzek, Jessica Pihl, Stine B Clemmensen, Willem Adriaan de Jongh, Thomas M Clausen, Giordano Nicoletti, Lorena Landuzzi, Manuel L Penichet, Tania Balboni, Marianna L Ianzano, Veronica Giusti, Thor G Theander, Morten A Nielsen, Ali Salanti, Pier-Luigi Lollini, Patrizia Nanni, Adam F Sander
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399413/cellular-vaccination-of-mlh1-mice-an-immunotherapeutic-proof-of-concept-study
#6
Claudia Maletzki, Yvonne Saara Gladbach, Mohamed Hamed, Georg Fuellen, Marie-Luise Semmler, Jan Stenzel, Michael Linnebacher
Mismatch-repair deficiency (MMR-D) is closely linked to hypermutation and accordingly, high immunogenicity. MMR-D-related tumors thus constitute ideal vaccination targets for both therapeutic and prophylactic approaches. Herein, the prophylactic and therapeutic impact of a cellular vaccine on tumor growth and tumor-immune microenvironment was studied in a murine MLH1-/- knockout mouse model. Prophylactic application of the lysate (+/- CpG ODN 1826) delayed tumor development, accompanied by increased levels of circulating T cell numbers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399412/a-virus-like-particle-immunotherapy-targeting-epitope-specific-anti-xct-expressed-on-cancer-stem-cell-inhibits-the-progression-of-metastatic-cancer-in-vivo
#7
Elisabetta Bolli, John P O'Rourke, Laura Conti, Stefania Lanzardo, Valeria Rolih, Jayne M Christen, Giuseppina Barutello, Marco Forni, Federica Pericle, Federica Cavallo
Aggressive forms of breast cancer, such as Her2+ and triple negative breast cancer (TNBC), are enriched in breast cancer stem cells (BCSC) and have limited therapeutic options. BCSC represent a key cellular reservoir for relapse, metastatic progression and therapeutic resistance. Their ability to resist common cytotoxic therapies relies on different mechanisms, including improved detoxification. The cystine-glutamate antiporter protein xCT (SLC7A11) regulates cystine intake, conversion to cysteine and subsequent glutathione synthesis, protecting cells against oxidative and chemical insults...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399411/monocytes-macrophages-promote-vascular-cxcr4-expression-via-the-erk-pathway-in-hepatocellular-carcinoma
#8
Ya-Ming Meng, Jing Liang, Chong Wu, Jing Xu, Dan-Ni Zeng, Xing-Juan Yu, Huiheng Ning, Li Xu, Limin Zheng
We recently identified CXCR4 as a novel vascular marker for vessel sprouting in hepatocellular carcinoma (HCC) tissues. Thus, CXCR4+ endothelial cells (ECs) could serve as a potential predictor for patients who may benefit from sorafenib treatment; however, the mechanism that regulates vascular CXCR4 expression in HCC remains largely unknown. Here, we revealed a large number of monocytes/macrophages (Mo/Mϕ) to be selectively enriched in the perivascular areas of CXCR4+ vessels in HCC samples. The depletion of Mo/Mϕ with gadolinium chloride (GdCl3) or zoledronic acid (ZA) treatment significantly reduced vascular CXCR4 expression in HCC tumors...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399410/poly-i-c-primes-primary-human-glioblastoma-cells-for-an-immune-response-invigorated-by-pd-l1-blockade
#9
Jorrit De Waele, Elly Marcq, Jonas Rm Van Audenaerde, Jinthe Van Loenhout, Christophe Deben, Karen Zwaenepoel, Erik Van de Kelft, David Van der Planken, Tomas Menovsky, Johan Mj Van den Bergh, Yannick Willemen, Patrick Pauwels, Zwi N Berneman, Filip Lardon, Marc Peeters, An Wouters, Evelien Lj Smits
Prognosis of glioblastoma remains dismal, underscoring the need for novel therapies. Immunotherapy is generating promising results, but requires combination strategies to unlock its full potential. We investigated the immunomodulatory capacities of poly(I:C) on primary human glioblastoma cells and its combinatorial potential with programmed death ligand (PD-L) blockade. In our experiments, poly(I:C) stimulated expression of both PD-L1 and PD-L2 on glioblastoma cells, and a pro-inflammatory secretome, including type I interferons (IFN) and chemokines CXCL9, CXCL10, CCL4 and CCL5...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399409/development-of-chimeric-antigen-receptors-targeting-t-cell-malignancies-using-two-structurally-different-anti-cd5-antigen-binding-domains-in-nk-and-crispr-edited-t-cell-lines
#10
Sunil S Raikar, Lauren C Fleischer, Robert Moot, Andrew Fedanov, Na Yoon Paik, Kristopher A Knight, Christopher B Doering, H Trent Spencer
Relapsed T-cell malignancies have poor outcomes when treated with chemotherapy, but survival after allogeneic bone marrow transplantation (BMT) approaches 50%. A limitation to BMT is the difficulty of achieving remission prior to transplant. Chimeric antigen receptor (CAR) T-cell therapy has shown successes in B-cell malignancies. This approach is difficult to adapt for the treatment of T-cell disease due to lack of a T-lymphoblast specific antigen and the fratricide of CAR T cells that occurs with T-cell antigen targeting...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399408/oncolytic-viruses-sensitize-human-tumor-cells-for-ny-eso-1-tumor-antigen-recognition-by-cd4-effector-t-cells
#11
Tiphaine Delaunay, Mathilde Violland, Nicolas Boisgerault, Soizic Dutoit, Virginie Vignard, Christian Münz, Monique Gannage, Brigitte Dréno, Kristine Vaivode, Dace Pjanova, Nathalie Labarrière, Yaohe Wang, E Antonio Chiocca, Fabrice Le Boeuf, John C Bell, Philippe Erbs, Frédéric Tangy, Marc Grégoire, Jean-François Fonteneau
Oncolytic immunotherapy using oncolytic viruses (OV) has been shown to stimulate the antitumor immune response by inducing the release of tumor-associated antigens (TAA) and danger signals from the dying infected tumor cells. In this study, we sought to determine if the lysis of tumor cells induced by different OV: measles virus, vaccinia virus, vesicular stomatitis virus, herpes simplex type I virus, adenovirus or enterovirus, has consequences on the capacity of tumor cells to present TAA, such as NY-ESO-1...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399407/beta-blocker-use-correlates-with-better-overall-survival-in-metastatic-melanoma-patients-and-improves-the-efficacy-of-immunotherapies-in-mice
#12
Kathleen M Kokolus, Ying Zhang, Jeffrey M Sivik, Carla Schmeck, Junjia Zhu, Elizabeth A Repasky, Joseph J Drabick, Todd D Schell
Immunotherapy has expanded treatment options for cancers with historically poor outcomes, yet a significant proportion of patients still fail to achieve durable clinical benefit. We defined the contribution of β-adrenergic receptor (βAR) signaling, a component of the stress response, on success of immunotherapy for melanoma since the use of antagonists (β-blockers) is associated with improved clinical outcomes in some cancers. We show that metastatic melanoma patients who received immunotherapy had improved overall survival if they also received pan β-blockers...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399406/deep-sequencing-of-the-t-cell-receptor-visualizes-reconstitution-of-t-cell-immunity-in-mogamulizumab-treated-adult-t-cell-leukemia
#13
Takero Shindo, Kazutaka Kitaura, Hiroshi Ureshino, Kazuharu Kamachi, Masaharu Miyahara, Kazuko Doi, Tatsuro Watanabe, Eisaburo Sueoka, Tadasu Shin-I, Ryuji Suzuki, Shinya Kimura
Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399405/genomic-landscape-of-advanced-basal-cell-carcinoma-implications-for-precision-treatment-with-targeted-and-immune-therapies
#14
Aaron M Goodman, Shumei Kato, Philip R Cohen, Amélie Boichard, Garrett Frampton, Vincent Miller, Philip J Stephens, Gregory A Daniels, Razelle Kurzrock
Metastatic basal cell cancer (BCC) is an ultra-rare malignancy with no approved therapies beyond Hedgehog inhibitors. We characterized the genomics, tumor mutational burden (TMB), and anti-PD-1 therapy responses in patients with locally advanced or metastatic BCC. Overall, 2,039 diverse cancer samples that had undergone comprehensive genomic profiling (CGP) were reviewed. Eight patients with locally advanced/metastatic BCC were identified (two had two CGP analyses; total, 10 biopsies). Two tumors demonstrated PD-L1 amplification...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399404/frequent-adaptive-immune-responses-against-arginase-1
#15
Evelina Martinenaite, Rasmus Erik Johansson Mortensen, Morten Hansen, Morten Orebo Holmström, Shamaila Munir Ahmad, Nicolai Grønne Dahlager Jørgensen, Özcan Met, Marco Donia, Inge Marie Svane, Mads Hald Andersen
The enzyme arginase-1 reduces the availability of arginine to tumor-infiltrating immune cells, thus reducing T-cell functionality in the tumor milieu. Arginase-1 is expressed by some cancer cells and by immune inhibitory cells, such as myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and its expression is associated with poor prognosis. In the present study, we divided the arginase-1 protein sequence into overlapping 20-amino-acid-long peptides, generating a library of 31 peptides covering the whole arginase-1 sequence...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399403/lack-of-mhc-class-ii-molecules-favors-cd8-t-cell-infiltration-into-tumors-associated-with-an-increased-control-of-tumor-growth
#16
Nada Chaoul, Alexandre Tang, Belinda Desrues, Marine Oberkampf, Catherine Fayolle, Daniel Ladant, Alexander Sainz-Perez, Claude Leclerc
Regulatory T-cells (Tregs) are crucial for the maintenance of immune tolerance and homeostasis as well as for preventing autoimmune diseases, but their impact on the survival of cancer patients remains controversial. In the TC-1 mouse model of human papillomavirus (HPV)-related carcinoma, we have previously demonstrated that the therapeutic efficacy of the CyaA-E7-vaccine, targeting the HPV-E7 antigen, progressively declines with tumor growth, in correlation with increased intratumoral recruitment of Tregs...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399402/prognostic-relevance-of-tumor-infiltrating-lymphocytes-and-immune-checkpoints-in-pediatric-medulloblastoma
#17
Jeroen F Vermeulen, Wim Van Hecke, Elisabeth J M Adriaansen, Mieke K Jansen, Rianne G Bouma, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Wim G M Spliet, Marcel Kool, Niels Bovenschen
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399401/a-safe-and-highly-efficient-tumor-targeted-type-i-interferon-immunotherapy-depends-on-the-tumor-microenvironment
#18
Anje Cauwels, Sandra Van Lint, Geneviève Garcin, Jennyfer Bultinck, Franciane Paul, Sarah Gerlo, José Van der Heyden, Yann Bordat, Dominiek Catteeuw, Lode De Cauwer, Elke Rogge, Annick Verhee, Gilles Uzé, Jan Tavernier
Despite approval for the treatment of various malignancies, clinical application of cytokines such as type I interferon (IFN) is severely impeded by their systemic toxicity. AcTakines (Activity-on-Target cytokines) are optimized immunocytokines that, when injected in mice, only reveal their activity upon cell-specific impact. We here show that type I IFN-derived AcTaferon targeted to the tumor displays strong antitumor activity without any associated toxicity, in contrast with wild type IFN. Treatment with CD20-targeted AcTaferon of CD20+ lymphoma tumors or melanoma tumors engineered to be CD20+, drastically reduced tumor growth...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399400/harnessing-innate-lung-anti-cancer-effector-functions-with-a-novel-bacterial-derived-immunotherapy
#19
Mark Bazett, Amanda M Costa, Momir Bosiljcic, Rebecca M Anderson, Matthew P Alexander, Stephanie W Y Wong, Salim Dhanji, Jenny Mh Chen, Jim Pankovich, Stephen Lam, Simon Sutcliffe, Hal Gunn, Shirin Kalyan, David W Mullins
Acute infection is known to induce strong anti-tumor immune responses, but clinical translation has been hindered by the lack of an effective strategy to safely and consistently provoke a therapeutic response. These limitations are overcome with a novel treatment approach involving repeated subcutaneous delivery of a Klebsiella-derived investigational immunotherapeutic, QBKPN. In preclinical models of lung cancer, QBKPN administration consistently showed anti-cancer efficacy, which was dependent on Klebsiella pre-exposure, but was independent of adaptive immunity...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29399399/bromodomain-inhibition-exerts-its-therapeutic-potential-in-malignant-pleural-mesothelioma-by-promoting-immunogenic-cell-death-and-changing-the-tumor-immune-environment
#20
Chiara Riganti, Marcello Francesco Lingua, Iris Chiara Salaroglio, Chiara Falcomatà, Luisella Righi, Deborah Morena, Francesca Picca, Daniele Oddo, Joanna Kopecka, Monica Pradotto, Roberta Libener, Sara Orecchia, Paolo Bironzo, Valentina Comunanza, Federico Bussolino, Silvia Novello, Giorgio Vittorio Scagliotti, Federica Di Nicolantonio, Riccardo Taulli
Systemic treatment of malignant pleural mesothelioma (MPM) is moderately active for the intrinsic pharmacological resistance of MPM cell and its ability to induce an immune suppressive environment. Here we showed that the expression of bromodomain (BRD) proteins BRD2, BRD4 and BRD9 was significantly higher in human primary MPM cells compared to normal mesothelial cells (HMC). Nanomolar concentrations of bromodomain inhibitors (BBIs) JQ1 or OTX015 impaired patient-derived MPM cell proliferation and induced cell-cycle arrest without affecting apoptosis...
2018: Oncoimmunology
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