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Immunogenic cell death

Lorenzo Galluzzi, Aitziber Buqué, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Immunogenicity depends on two key factors: antigenicity and adjuvanticity. The presence of exogenous or mutated antigens explains why infected cells and malignant cells can initiate an adaptive immune response provided that the cells also emit adjuvant signals as a consequence of cellular stress and death. Several infectious pathogens have devised strategies to control cell death and limit the emission of danger signals from dying cells, thereby avoiding immune recognition. Similarly, cancer cells often escape immunosurveillance owing to defects in the molecular machinery that underlies the release of endogenous adjuvants...
October 17, 2016: Nature Reviews. Immunology
Zhao Luo, Xue-Wei Cao, Chen Li, Miao-Dan Wu, Xu-Zhong Yang, Jian Zhao, Fu-Jun Wang
Cell-penetrating peptides (CPPs) have been shown to be potential drug carriers for cancer therapy. The inherently low immunogenicity and cytotoxicity of human-derived CPPs make them more suitable for intracellular drug delivery compared to other delivery vehicles. In this work, the protein transduction ability of a novel CPP (termed HBP) derived from the heparin-binding domain of HB-EGF was evaluated. Our data shows, for the first time, that HBP possesses similar properties to typical CPPs and is a potent drug delivery vector for improving the antitumor activity of impermeable MAP30...
October 14, 2016: Journal of Peptide Science: An Official Publication of the European Peptide Society
Martin Tobias Speth, Urska Repnik, Gareth Griffiths
Tuberculosis (TB) is a major disease burden globally causing more than 1.5 million deaths per year. The attenuated live vaccine strain Bacille Calmette-Guérin (BCG), although providing protection against childhood TB, is largely ineffective against adult pulmonary TB. A major aim therefore is to increase the potency of the BCG vaccine to generate stronger and more sustained immunity against TB. Here, we investigated the use of layer-by-layer (LbL) nanocoating of the surface of live BCG with several layers of polyinosinic-polycytidylic acid (poly(I:C)), a strong inducer of cell-mediated immunity, and the biodegradable polysaccharide chitosan to enhance BCG immunogenicity...
September 30, 2016: Biomaterials
Bradley J Monk, Andrea Facciabene, William E Brady, Carol Aghajanian, Paula M Fracasso, Joan Walker, Heather A Lankes, Kristi L Manjarrez, Gwenn Danet-Desnoyers, Katherine M Bell-McGuinn, Carolyn K McCourt, Alexander Malykhin, Robert M Hershberg, George Coukos
BACKGROUND: Immunotherapy is an emerging paradigm for the treatment of cancer, but the potential efficacy of many drugs cannot be sufficiently tested in the mouse. We sought to develop a rational combination of motolimod-a novel Toll-like receptor 8 (TLR8) agonist that stimulates robust innate immune responses in humans but diminished responses in mice-with pegylated liposomal doxorubicin (PLD), a chemotherapeutic that induces immunogenic cell death. METHODS: We followed an integrative pharmacologic approach including healthy human volunteers, non-human primates, NSG-HIS ("humanized immune system") mice reconstituted with human CD34+ cells, and cancer patients to test the effects of motolimod and to assess the combination of motolimod with PLD for the treatment of ovarian cancer...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Soheila Moeini, Mohsen Saeidi, Fatemeh Fotouhi, Mahdieh Mondanizdeh, Sadegh Shirian, Alireza Mohebi, Ali Gorji, Amir Ghaemi
The use of DNA vaccines has become an attractive approach for generating antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of DNA vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) can be improved by using an adjuvant injected together with checkpoint antibodies. In the current study, we evaluated whether the therapeutic effects of a DNA vaccine encoding human papilloma virus type 16 (HPV-16) E7 can be enhanced by combined application of an immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway and secondary lymphoid tissue chemokine (SLC) also known as CCL21 adjuvant, in a mouse cervical cancer model...
October 3, 2016: Archives of Virology
Alessia Mennitto, Paolo Grassi, Raffaele Ratta, Elena Verzoni, Michele Prisciandaro, Giuseppe Procopio
Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α)...
October 2016: Therapeutic Advances in Urology
Yuejuan Yao, Jiexian Jing
The death of patients with gastric cancer is mainly due to its recurrence and metastasis, and circulating tumor cell (CTC) is the necessary condition of metastasis. As liquid biopsy, CTC detection has its certain clinical significance. The detection is required after enrichment because circulating tumor cells are rare. Many enrichment methods have been developed: methods based on physical characteristics of TCT, like density, size and dielectric properties and so on; immunogenicity, like Cell Search System; and microfluidic chip technology...
September 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
J Ng, E Golden, D Stuff, J Khani, I Shuryak, A Harken, D J Brenner, S Formenti
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
María José García Cebrián, Monika Bauden, Roland Andersson, Stefan Holdenrieder, Daniel Ansari
Pancreatic cancer has a dismal prognosis and there is an increasing and unmet need to identify better diagnostic and therapeutic targets in order to ameliorate the course of the disease. HMGB1, a nuclear DNA-binding protein that acts as a transcription factor, is currently in the limelight. HMGB1 exhibits a dual role in pancreatic cancer; when intracellular, it acts as an anti-tumor protein stabilizing the genome, whereas extracellular HMGB1 behaves as a pro-tumor protein with cytokine, chemokine and growth factor functions...
September 2016: Anticancer Research
Sarah Maria Johler, Jörg Fuchs, Guido Seitz, Sorin Armeanu-Ebinger
Macrophage migration inhibitory factor (MIF) is known to be involved in oncogenic transformation, tumour progression, and immunosuppression and is overexpressed in many solid tumours, including paediatric rhabdomyosarcoma (RMS). We investigated the function of MIF in RMS during treatment with cytotoxic drugs. RMS cell lines were analysed by flow cytometry, immunofluorescence staining, and ELISA. We demonstrated the overexpression of MIF in RMS cells and the enhanced expression and secretion after treatment with cytotoxic agents...
September 15, 2016: Cancer Immunology, Immunotherapy: CII
Stefania Di Blasio, Inge M N Wortel, Diede A G van Bladel, Laura E de Vries, Tjitske Duiveman-de Boer, Kuntal Worah, Nienke de Haas, Sonja I Buschow, I Jolanda M de Vries, Carl G Figdor, Stanleyson V Hato
Chemotherapeutics, including the platinum compounds oxaliplatin (OXP) and cisplatin (CDDP), are standard care of treatment for cancer. Although chemotherapy has long been considered immunosuppressive, evidence now suggests that certain cytotoxic agents can efficiently stimulate antitumor responses, through the induction of a form of apoptosis, called immunogenic cell death (ICD). ICD is characterized by exposure of calreticulin and heat shock proteins (HSPs), secretion of ATP and release of high-mobility group box 1 (HMGB1)...
August 2016: Oncoimmunology
Mani H Vemula, Raghavender Medisetti, Rakesh Ganji, Kiran Jakkala, Swetha Sankati, Kiranam Chatti, Sharmistha Banerjee
Zinc metalloprotease-1 (Zmp1) from Mycobacterium tuberculosis (M.tb), the tuberculosis (TB) causing bacillus, is a virulence factor involved in inflammasome inactivation and phagosome maturation arrest. We earlier reported that Zmp1 was secreted under granuloma-like stress conditions, induced Th2 cytokine microenvironment and was highly immunogenic in TB patients as evident from high anti-Zmp1 antibody titers in their sera. In this study, we deciphered a new physiological role of Zmp1 in mycobacterial dissemination...
2016: Frontiers in Microbiology
Motoko Sasaki, Yasuni Nakanuma
Various cellular responses including apoptosis, necrosis, autophagy and cellular senescence are involved in the pathogenesis of inflammatory cholangiopathies, such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and biliary atresia (BA). For example, dysregulated autophagy may play a role in abnormal expression of mitochondrial antigens and following autoimmune pathogenesis in bile duct lesions in PBC. Recently, new types of regulated cell death including necroptosis, parthanatos, pyroptosis, immunogenic cell death are the subject of numerous reports and they may play roles in pathogenesis of liver diseases, such as nonalcoholic steatohepatitis...
September 8, 2016: Clinics and Research in Hepatology and Gastroenterology
Charlotte S Lo, Sanaz Sanii, David R Kroeger, Katy Milne, Aline Talhouk, Derek S Chiu, Kurosh Rahimi, Patricia A Shaw, Blaise A Clarke, Brad H Nelson
PURPOSE: Some forms of chemotherapy can enhance anti-tumor immunity through immunogenic cell death, resulting in increased T cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunological changes consistent with this possibility. METHODS: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors...
September 6, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tobias Weiss, Michael Weller, Patrick Roth
INTRODUCTION: The mainstays of brain tumor therapy are surgery, radiotherapy and chemotherapy. Cancer immunotherapy is explored as an additional treatment modality. However, emerging evidence indicates that also radio- and chemotherapy have immunological effects in addition to their cytotoxic and cytostatic activities. AREA COVERED: We summarize the literature on radio- and chemotherapy-mediated immunological effects in primary and secondary brain tumors and outline open questions within the field...
October 2016: Expert Review of Anticancer Therapy
Heng Zhou, Allan Sauvat, Lígia C Gomes-da-Silva, Sylvère Durand, Sabrina Forveille, Kristina Iribarren, Takahiro Yamazaki, Sylvie Souquere, Lucillia Bezu, Kevin Müller, Marion Leduc, Peng Liu, Liwei Zhao, Aurélien Marabelle, Laurence Zitvogel, Øystein Rekdal, Oliver Kepp, Guido Kroemer
LTX-401 is an oncolytic amino acid derivative with potential immunogenic properties. Here, we demonstrate that LTX-401 selectively destroys the structure of the Golgi apparatus, as determined by means of ultrastructural analyses and fluorescence microscopic observation of cells expressing Golgi-targeted GFP reporters. Subcellular fractionation followed by mass spectrometric detection revealed that LTX-401 selectively enriched in the Golgi rather than in mitochondria or in the cytosol. The Golgi-dissociating agent Brefeldin A (BFA) reduced cell killing by LTX-401 as it partially inhibited LTX-401-induced mitochondrial release of cytochrome c and the activation of BAX...
September 2, 2016: Cell Death and Differentiation
Cristina Migali, Monica Milano, Dario Trapani, Carmen Criscitiello, Angela Esposito, Marzia Locatelli, Ida Minchella, Giuseppe Curigliano
Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity. This heterogeneity enhances the 'danger signals' and select clone variants that could be more antigenic or, in other words, that could more strongly stimulate a host immune antitumor response...
September 2016: Therapeutic Advances in Medical Oncology
Guy R Simpson, Kate Relph, Kevin Harrington, Alan Melcher, Hardev Pandha
Oncolytic viruses are multifunctional anticancer agents with huge clinical potential, and have recently passed the randomized Phase III clinical trial hurdle. Both wild-type and engineered viruses have been selected for targeting of specific cancers, to elicit cytotoxicity, and also to generate antitumor immunity. Single-agent oncolytic virotherapy treatments have resulted in modest effects in the clinic. There is increasing interest in their combination with cytotoxic agents, radiotherapy and immune-checkpoint inhibitors...
2016: Oncolytic Virotherapy
Kuangda Lu, Chunbai He, Nining Guo, Christina Chan, Kaiyuan Ni, Ralph R Weichselbaum, Wenbin Lin
Photodynamic therapy (PDT) can destroy local tumors and minimize normal tissue damage, but is ineffective at eliminating metastases. Checkpoint blockade immunotherapy has enjoyed recent success in the clinic, but only elicits limited rates of systemic antitumor response for most cancers due to insufficient activation of the host immune system. Here we describe a treatment strategy that combines PDT by a new chlorin-based nanoscale metal-organic framework (nMOF), TBC-Hf, and a small-molecule immunotherapy agent that inhibits indoleamine 2,3-dioxygenase (IDO), encapsulated in the nMOF channels to induce systemic antitumor immunity...
September 28, 2016: Journal of the American Chemical Society
Elham Beyranvand Nejad, Tetje C van der Sluis, Suzanne van Duikeren, Hideo Yagita, George M Janssen, Peter A van Veelen, Cornelis J M Melief, Sjoerd H van der Burg, Ramon Arens
Certain cytotoxic chemotherapeutic drugs are immunogenic, stimulating tumor immunity through mechanisms that are not completely understood. Here we show how the DNA-damaging drug cisplatin modulates tumor immunity. At the maximum tolerated dose (MTD), cisplatin cured 50% of mice with established murine TC-1 or C3 tumors, which are preclinical models of human papillomavirus (HPV)-associated cancer. Notably, the curative benefit of cisplatin relied entirely upon induction of tumor-specific CD8(+) T cells. Mechanistic investigations showed that cisplatin stimulated tumor infiltration of inflammatory antigen-presenting cells (APC) expressing relatively higher levels of the T-cell costimulatory ligands CD70, CD80, and CD86...
October 15, 2016: Cancer Research
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