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https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#1
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29146441/combining-immunotherapies-for-the-treatment-of-prostate-cancer
#2
REVIEW
Jason M Redman, James L Gulley, Ravi A Madan
Sipuleucel-T, a therapeutic dendritic-cell vaccine, was Food and Drug Administration-approved for prostate cancer in 2010. No new immunotherapies for prostate cancer have been approved since. However, novel agents and combination approaches offer great promise for improving outcomes for prostate cancer patients. Here we review the latest developments in immunotherapy for prostate cancer. Sipuleucel-T has demonstrated a survival advantage of 4.1 months in metastatic castration-resistant prostate cancer. PSA-TRICOM (PROSTVAC), a prostate-specific antigen-targeted vaccine platform, showed evidence of clinical and immunologic efficacy in early-phase clinical trials, and results from a phase III trial in advanced disease are pending...
December 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29146244/extending-antigen-release-from-particulate-vaccines-results-in-enhanced-antitumor-immune-response
#3
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, David Sailer, J Christopher Luft, Joseph M DeSimone
Tumor-specific CD8(+) cytotoxic T lymphocytes (CTLs) play a critical role in an anti-tumor immune response. However, vaccination intended to elicit a potent CD8(+) T cell responses employing tumor-associated peptide antigens, are typically ineffective due to poor immunogenicity. Previously, we engineered a polyethylene glycol (PEG) hydrogel-based subunit vaccine for the delivery of an antigenic peptide and CpG (adjuvant) to elicit potent CTLs. In this study, we further examined the effect of antigen release kinetics on their induced immune responses...
November 13, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#4
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have shown that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate anti-tumor immune responses. However, it remains unclear how ICD can be exploited for cancer immunotherapy. Here, we present a new biomaterial-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their immunogenicity in murine models of melanoma and colon carcinoma...
November 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/29143804/telomeres-and-telomerase-in-hematopoietic-dysfunction-prognostic-implications-and-pharmacological-interventions
#5
REVIEW
Theresa Vasko, Andrea Kaifie, Matthias B Stope, Thomas Kraus, Patrick Ziegler
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML), indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes (BMFS)...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29143359/indolent-t-lymphoblastic-proliferation-concomitant-to-acinic-cell-carcinoma-mimicking-t-lymphoblastic-lymphoma-case-report-and-literature-review
#6
Hajime Yasuda, Miyuki Tsutsui, Yasunori Ota, Masaru Tanaka, Norio Komatsu
Indolent T-lymphoblastic proliferation (iT-LBP) is a non-clonal benign condition showing extrathymic proliferation of T-lymphoblasts positive for CD3, CD4, CD8, and TdT. Isolated iT-LBP has been observed, but the majority of iT-LBP have been seen in conjunction with other disorders including Castleman disease, hepatocellular carcinoma, follicular dendritic cell tumors, angioimmunoblastic T-cell lymphoma, myasthenia gravis, and acinic cell carcinoma (ACC). The clinical course of iT-LBP is indolent, and no therapy is usually required...
November 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29143114/cancer-vaccine-strategies-translation-from-mice-to-human-clinical-trials
#7
REVIEW
Jay A Berzofsky, Masaki Terabe, Jane B Trepel, Ira Pastan, David F Stroncek, John C Morris, Lauren V Wood
We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs)...
November 15, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29141219/preventive-inhibition-of-liver-tumorigenesis-by-systemic-activation-of-innate-immune-functions
#8
Jin Lee, Rui Liao, Gaowei Wang, Bi-Huei Yang, Xiaolin Luo, Nissi M Varki, Shuang-Jian Qiu, Bing Ren, Wenxian Fu, Gen-Sheng Feng
Liver cancer has become the second most deadly malignant disease, with no efficient targeted or immune therapeutic agents available yet. While dissecting the roles of cytoplasmic signaling molecules in hepatocarcinogenesis using an inducible mouse gene targeting system, Mx1-cre, we identified a potent liver tumor-inhibitory effect of synthetic double-stranded RNA (dsRNA), polyinosinic-polycytidylic acid (pIC), an inducer of the Mx1-cre system. Injection of pIC at the pre-cancer stage robustly suppressed liver tumorigenesis either induced by chemical carcinogens or by Pten loss and associated hepatosteatosis...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29140820/renal-effects-of-cytokines-in-hypertension
#9
Yi Wen, Steven D Crowley
PURPOSE OF REVIEW: Inflammatory cytokines contribute to the pathogenesis of hypertension through effects on renal blood flow and sodium handling. This review will update recent advances that explore the renal actions of immune cells and cytokines in the pathogenesis of hypertension. RECENT FINDINGS: Populations of cells from both the innate and adaptive immune systems contribute to hypertension by modulating functions of the vasculature and epithelial cells in the kidney...
November 14, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29138509/non-thermal-atmospheric-plasma-ameliorates-imiquimod-induced-psoriasis-like-skin-inflammation-in-mice-through-inhibition-of-immune-responses-and-up-regulation-of-pd-l1-expression
#10
Yun Sang Lee, Myung-Hoon Lee, Hang-Jun Kim, Ho-Ryun Won, Chul-Ho Kim
Plasma medicine is an emerging novel therapeutic field. It has been reported that plasma can kill bacteria, promote wound healing and induce apoptosis of tumor cells. However, the effects of plasma on immune cells and immune related skin diseases have not been well studied. In this study, we demonstrated that non-thermal atmospheric plasma (NTP) treatment could inhibit psoriasis-like skin inflammation in mice. NTP treatment in imiquimod-induced psoriasis-like mouse skin inhibited increases in epithelial cell thickness and expression of pro-inflammatory molecules compared to ones without the NTP treatment...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137271/environmental-conditions-differentially-affect-neurobehavioral-outcomes-in-a-mouse-model-of-sepsis-associated-encephalopathy
#11
Mu-Huo Ji, Hui Tang, Dan Luo, Li-Li Qiu, Min Jia, Hong-Mei Yuan, Shan-Wu Feng, Jian-Jun Yang
Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136686/-clinicopathologic-and-molecular-characteristics-of-malignant-gastrointestinal-neuroectodermal-tumors
#12
M Zhao, T W Zhao, J Ma, C Y Wu, L Chen, G Q Ru, X L He
Objective: To investigate the clinicopathologic and molecular characteristics, diagnostic, differential diagnostic and prognostic features of malignant gastrointestinal neuroectodermal tumor. Methods: Two cases of malignant gastrointestinal neuroectodermal tumor were retrieved; the clinical and radiologic features, histomorphology, immunophenotype, molecular genetics and prognosis were analyzed and the relevant literature reviewed. Results: Case 1 was a 57-year-old male, presented with recurrent abdominal pain and melena...
November 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29135371/follistatin-like-protein-1-upregulates-dendritic-cell-based-immunity-in-patients-with-nasopharyngeal-carcinoma
#13
Hong Wang, Shiping Huang, Senyong Wu, Shaolin Yin, Anzhou Tang, Wensheng Wen
Follistatin-like protein-1 (FSTL1) is an inflammatory factor that can induce an inflammatory response and is expressed in cancers. However, little is known about its content and function in nasopharyngeal carcinoma (NPC). Interleukin (IL)-12 and IL-4 are primarily secreted by dendritic cells (DCs) and activated T lymphocytes, respectively; these factors can induce Th cell differentiation and cytotoxic lymphocyte production, both of which facilitate tumors through the STAT4 and STAT6 pathways, respectively. In this study, the relationship between FSTL1 and both IL-12 and IL-4 as well as the functional mechanism of these cytokines was explored...
November 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/29133913/nitric-oxide-mediated-inhibition-of-antigen-presentation-from-dcs-to-cd4-t-cells-in-cancer-and-measurement-of-stat1-nitration
#14
Joseph Markowitz, Jiang Wang, Zach Vangundy, Jia You, Vedat Yildiz, Lianbo Yu, Isaac P Foote, Owen E Branson, Andrew R Stiff, Taylor R Brooks, Brandon Biesiadecki, Thomas Olencki, Susheela Tridandapani, Michael A Freitas, Tracey Papenfuss, Mitch A Phelps, William E Carson
Myeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4(+) T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#15
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129292/targeting-myeloid-cells-in-the-tumor-sustaining-microenvironment
#16
REVIEW
Jonathan Schupp, Franziska K Krebs, Niklas Zimmer, Emily Trzeciak, Detlef Schuppan, Andrea Tuettenberg
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29129094/rational-combination-of-immunotherapy-for-triple-negative-breast-cancer-treatment
#17
Chia-Wei Li, Seung-Oe Lim, Jennifer L Hsu, Mien-Chie Hung
Recent evidence indicates that tumor infiltrating lymphocytes (TILs), including cytotoxic T cells, are present in the tumor microenvironment of triple-negative breast cancers (TNBC). Despite the presence of cytotoxic T cells, these tumors still develop, progress, and metastasize, suggesting evasion of immune response. One mechanism of immunosuppression is the presence of the T cell inhibitory molecule, programmed death protein 1 (PD-1), on infiltrating T cells and its cognate ligand programmed death ligand 1 (PD-L1) on tumor cells, myeloid dendritic cells (DCs), and macrophages, in the tumor microenvironment...
October 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/29127106/a-melanin-mediated-cancer-immunotherapy-patch
#18
Yanqi Ye, Chao Wang, Xudong Zhang, Quanyin Hu, Yuqi Zhang, Qi Liu, Di Wen, Joshua Milligan, Adriano Bellotti, Leaf Huang, Gianpietro Dotti, Zhen Gu
Melanin is capable of transforming 99.9% of the absorbed sunlight energy into heat, reducing the risk of skin cancer. We here develop a melanin-mediated cancer immunotherapy strategy through a transdermal microneedle patch. B16F10 whole tumor lysate containing melanin is loaded into polymeric microneedles that allow sustained release of the lysate upon insertion into the skin. In combination with the near-infrared light irradiation, melanin in the patch mediates the generation of heat, which further promotes tumor-antigen uptake by dendritic cells, and leads to enhanced antitumor vaccination...
November 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/29123946/tumor-cell-death-by-pattern-sensing-of-exogenous-rna-tumor-cell-tlr3-directly-induces-necroptosis-by-poly-i-c-in-vivo-independent-of-immune-effector-mediated-tumor-shrinkage
#19
Hiromi Takaki, Hiroaki Shime, Misako Matsumoto, Tsukasa Seya
Poly(I:C) acts on dendritic cells to induce potent antitumor effects through the production of cytokines/interferons, activation of natural killer cells and proliferation of cytotoxic T lymphocytes. In some tumor or myeloid lineages, poly(I:C) seemed to induce necroptosis in concert with a pan-caspase inhibitor by directly acting on toll-like receptor (TLR) 3 in both in vivo and in vitro models.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29122656/programmed-death-1-ligands-pd-l1-and-pd-l2-show-distinctive-and-restricted-patterns-of-expression-in-lymphoma-subtypes
#20
Poonam K Panjwani, Vivek Charu, Monique DeLisser, Hernan Molina-Kirsch, Yasodha Natkunam, Shuchun Zhao
The success of immunotherapy using immune checkpoint blockade in solid tumors and in relapsed/refractory classical Hodgkin lymphoma and chronic lymphocytic leukemia holds promise for targeted therapy in hematologic malignancies. Since efficacy of immunomodulatory therapy is correlated with numbers of cells that express programmed death (PD-1) ligands, we evaluated the expression of PD-L1 and PD-L2 proteins using immunohistochemistry in over 702 diagnostic lymphoma biopsies. In classical Hodgkin lymphoma, PD-L1 and PD-L2 were expressed in 82% and 41% of cases respectively, and PD-L1 but not PD-L2 expression correlated with Epstein Barr Virus in tumor cells...
November 6, 2017: Human Pathology
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