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Cancer AND Immune System

Juan M R Albano, Lígia Nunes de Morais Ribeiro, Verônica Muniz Couto, Mariana Barbosa Messias, Gustavo Henrique Rodrigues da Silva, Márcia Cristina Breitkreitz, Eneida de Paula, Monica Pickholz
In this work, a stable nanocarrier for the anti-cancer drug docetaxel was rational designed. The nanocarrier was developed based on the solid lipid nanoparticle preparation process aiming to minimize the total amount of excipients used in the final formulations. A particular interest was put on the effects of the polymers in the final composition. In this direction, two poloxoamers -Pluronic F127 and F68- were selected. Some poloxamers are well known to be inhibitors of the P-glycoprotein efflux pump. Additionally, their poly-ethylene-oxide blocks can help them to escape the immune system, making the poloxamers appealing to be present in a nanoparticle designed for the treatment of cancer...
November 28, 2018: Colloids and Surfaces. B, Biointerfaces
Tianqun Lang, Yiran Liu, Zhong Zheng, Wei Ran, Yihui Zhai, Qi Yin, Pengcheng Zhang, Yaping Li
Metastatic breast cancer may be resistant to chemo-immunotherapy due to the existence of cancer stem cells (CSC). And the control of particle size and drug release of a drug carrier for multidrug combination is a key issue influencing therapy effect. Here, a cocktail strategy is reported, in which chemotherapy against both bulk tumor cells and CSC and immune checkpoint blockade therapy are intergraded into one drug delivery system. The chemotherapeutic agent paclitaxel (PTX), the anti-CSC agent thioridazine (THZ), and the PD-1/PD-L1 inhibitor HY19991 (HY) are all incorporated into an enzyme/pH dual-sensitive nanoparticle with a micelle-liposome double-layer structure...
December 5, 2018: Advanced Materials
Vardhman Kumar, Shyni Varghese
The emergence of immunotherapies and recent FDA approval of several of them makes them a promising therapeutic strategy for cancer. While these advancements underscore the potential of engaging the immune system to target tumors, this approach has so far been efficient only for certain cancers. Extending immunotherapy as a widely acceptable treatment for various cancers requires a deeper understanding of the interactions of tumor cells within the tumor microenvironment (TME). The immune cells are a key component of the TME, which also includes other stromal cells, soluble factors, and extracellular matrix-based cues...
December 5, 2018: Advanced Healthcare Materials
Ahmed Ibrahim, Luisa Hugerth, Linnea Hases, Ashish Saxena, Maike Seifert, Quentin Thomas, Jan-Åke Gustafsson, Lars Engstrand, Cecilia Williams
Chronic inflammation of the colon (colitis) is a risk factor for colorectal cancer (CRC). Hormone-replacement therapy reduces CRC incidences, and the estrogen receptor beta (ERβ/ESR2) has been implicated in this protection. Gut microbiota is altered in both colitis and CRC and may influence the severity of both. Here we test the hypothesis that intestinal ERβ impacts the gut microbiota. Mice with and without intestine-specific deletion of ERβ (ERβKOVil ) were generated using the Cre-LoxP system. Colitis and CRC were induced with a single intraperitoneal injection of azoxymethane (AOM) followed by administration of three cycles of dextran sulfate sodium (DSS) in drinking water...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Neha Kaushik, Seungmo Kim, Yongjoon Suh, Su-Jae Lee
Cancer is a systemic disease in which neoplastic cells interact with multiple types of non-neoplastic stromal cells as well as non-cellular components. The extracellular matrix (ECM) is a non-cellular component that is aberrantly regulated in many types of tumor microenvironments. Since the ECM generally maintains the tissue structure and provides mechanical forces in the tumor microenvironment, it has been simply assumed to act as a physical barrier for cancer metastasis and have a passive role in cancer progression...
December 4, 2018: Archives of Pharmacal Research
Soizic Garaud, Pawel Zayakin, Laurence Buisseret, Undine Rulle, Karina Silina, Alexandre de Wind, Gert Van den Eyden, Denis Larsimont, Karen Willard-Gallo, Aija Linē
An important role for tumor infiltrating B lymphocytes (TIL-B) in the immune response to cancer is emerging; however, very little is known about the antigen specificity of antibodies produced in situ . The presence of IgA antibodies in the tumor microenvironment has been noted although their biological functions and clinical significance are unknown. This study used a 91-antigen microarray to examine the IgG and IgA autoantibody repertoires in breast cancer (BC). Tumor and adjacent breast tissue supernatants and plasma from BC patients together with normal breast tissue supernatants and plasma from healthy controls (patients undergoing mammary reduction and healthy blood donors) were analyzed to investigate relationships between autoantibodies and the clinical, histological and immunological features of tumors...
2018: Frontiers in Immunology
Jiao Wang, Kyle B Lupo, Andrea M Chambers, Sandro Matosevic
BACKGROUND: The anti-tumor immunity of natural killer (NK) cells can be paralyzed by the CD73-induced generation of immunosuppressive adenosine from precursor ATP within the hypoxic microenvironment of solid tumors. In an effort to redirect purinergic immunosuppression of NK cell anti-tumor function, we showed, for the first time, that immunometabolic combination treatment with NKG2D-engineered CAR-NK cells alongside blockade of CD73 ectonucleotidase activity can result in significant anti-tumor responses in vivo...
December 4, 2018: Journal for Immunotherapy of Cancer
Junaid Raja, Johannes M Ludwig, Scott N Gettinger, Kurt A Schalper, Hyun S Kim
BACKGROUND: Immunotherapy is at the forefront of modern oncologic care. Various novel therapies have targeted all three layers of tumor biology: tumor, niche, and immune system with a range of promising results. One emerging class in both primary and salvage therapy is oncolytic viruses. This therapy offers a multimodal approach to specifically and effectively target and destroy malignant cells, though a barrier oncoviral therapies have faced is a limited therapeutic response to currently delivery techniques...
December 4, 2018: Journal for Immunotherapy of Cancer
Kevin Sek, Christina Mølck, Gregory D Stewart, Lev Kats, Phillip K Darcy, Paul A Beavis
The immune system plays a major role in the surveillance and control of malignant cells, with the presence of tumor infiltrating lymphocytes (TILs) correlating with better patient prognosis in multiple tumor types. The development of 'checkpoint blockade' and adoptive cellular therapy has revolutionized the landscape of cancer treatment and highlights the potential of utilizing the patient's own immune system to eradicate cancer. One mechanism of tumor-mediated immunosuppression that has gained attention as a potential therapeutic target is the purinergic signaling axis, whereby the production of the purine nucleoside adenosine in the tumor microenvironment can potently suppress T and NK cell function...
December 2, 2018: International Journal of Molecular Sciences
Michael H Gerber, Patrick W Underwood, Sarah M Judge, Daniel Delitto, Andrea E Delitto, Rachel L Nosacka, Bayli B DiVita, Ryan M Thomas, Jennifer B Permuth, Steven J Hughes, Shannon M Wallet, Andrew R Judge, Jose G Trevino
Cancer cachexia is a debilitating condition seen frequently in patients with pancreatic ductal adenocarcinoma (PDAC). The underlying mechanisms driving cancer cachexia are not fully understood but are related, at least in part, to the immune response to the tumor both locally and systemically. We hypothesize that there are unique differences in cytokine levels in the tumor microenvironment and systemic circulation between PDAC tumors and that these varying profiles affect the degree of cancer cachexia observed...
December 1, 2018: International Journal of Molecular Sciences
Bassel Akache, Felicity C Stark, Yimei Jia, Lise Deschatelets, Renu Dudani, Blair A Harrison, Gerard Agbayani, Dean Williams, Mohammad P Jamshidi, Lakshmi Krishnan, Michael J McCluskie
Archaeosomes are liposomes traditionally comprised of total polar lipids (TPL) or semi-synthetic glycerolipids of ether-linked isoprenoid phytanyl cores with varied glyco- and amino-head groups. As adjuvants, they induce robust, long-lasting humoral and cell-mediated immune responses and enhance protection in murine models of infectious disease and cancer. Traditional total polar lipid (TPL) archaeosome formulations are relatively complex and first generation semi-synthetic archaeosomes involve many synthetic steps to arrive at the final desired glycolipid composition...
2018: PloS One
Ioannis Koliarakis, Anna Psaroulaki, Taxiarchis Konstantinos Nikolouzakis, Markos N Sgantzos, George Goulielmos, Vasilis P Androutsopoulos, John Tsiaoussis
Colon holds a complex microbial community, which is crucial for maintaining homeostasis and regulating metabolic functions, supporting the intestinal barrier and controlling immune responses. Previous studies have supported a link between intestinal microbiota and colorectal cancer (CRC). Based on these fndings, the present review analyzed the numerous interactions that occur between microbiota and CRC, starting from the role of intestinal microbiota in colonic homoeostasis. Intestinal microbiota is a cause of CRC and involves various mechanisms such as chronic inflammation, the production of genotoxins causing DNA impairment and/or the biosynthesis of toxic compounds...
September 2018: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Sanam Sadreddini, Behzad Baradaran, Ali Aghebati-Maleki, Sevil Sadreddini, Dariush Shanehbandi, Ali Fotouhi, Leili Aghebati-Maleki
Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors...
December 3, 2018: Journal of Cellular Physiology
Noah Sorrelle, Debolina Ganguly, Adrian T A Dominguez, Yuqing Zhang, Huocong Huang, Lekh N Dahal, Natalie Burton, Arturas Ziemys, Rolf A Brekken
Immune profiling of tissue through multiplex immunohistochemistry is important for the investigation of immune cell dynamics, and it can contribute to disease prognosis and evaluation of treatment response in cancer patients. However, protocols for mouse formalin-fixed, paraffin-embedded tissue have been less successful. Given that formalin fixation and paraffin embedding remains the most common preparation method for processing mouse tissue, this has limited the options to study the immune system and the impact of novel therapeutics in preclinical models...
December 3, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Silvia Piconese, Ilenia Cammarata, Vincenzo Barnaba
In the present review, we analyzed the various overlapping and non-mutually exclusive mechanisms that intersect and form complex and highly flexible immunological networks allowing the defense against liver infections and tumors. Liver immunity results from the combination of the skills of systemic and local immune system(s) to sense and recognize pathogen or tumor antigens, to sensitize a wide range of innate and adaptive immune cells, and to clear the "invaders", through the establishment of a transient liver immunopathology state undergoing resolution/control of infections or tumors, and memory development...
December 2018: Journal of Autoimmunity
Tanja Fehm, Volkmar Müller
Within the last years significant improvements have been achieved in early and metastatic breast cancer treatment by innovative targeted therapies and new drug combinations. GnRH-analogues have been confirmed as an important part of endocrine treatment in premenopausal patients. Endocrine based strategies including CDK-4/6-Inhibitors substantially improve progression-free survival in metastatic patients. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has achieved a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer...
December 2018: Deutsche Medizinische Wochenschrift
Huangliang Zheng, Jiaqi Li, Xiang Luo, Cong Li, Ling Hu, Qiujun Qiu, Junqiang Ding, Yanzhi Song, Yihui Deng
Macrophage-mediated drug delivery system has emerged and gained wide interest as a novel strategy for cancer treatment. Among them, RAW264.7 cell was commonly used as the macrophage model for antitumor drug loading and delivery. However, this cell line was a macrophage-like cancerous cell with both immunogenicity and pro-tumorigenic properties, which may interfere with the positive response of the host immune system to developed tumor. Thus, the safety and efficacy of the RAW264.7 cell line as a drug carrier for cancer therapy remain questionable...
November 30, 2018: Cancer Chemotherapy and Pharmacology
Ruchi Chaudhary, Luca Quagliata, Jermann Philip Martin, Ilaria Alborelli, Dinesh Cyanam, Vinay Mittal, Warren Tom, Janice Au-Young, Seth Sadis, Fiona Hyland
Background: Tumor mutational burden (TMB) is an increasingly important biomarker for immune checkpoint inhibitors. Recent publications have described strong association between high TMB and objective response to mono- and combination immunotherapies in several cancer types. Existing methods to estimate TMB require large amount of input DNA, which may not always be available. Methods: In this study, we develop a method to estimate TMB using the Oncomine Tumor Mutation Load (TML) Assay with 20 ng of DNA, and we characterize the performance of this method on various formalin-fixed, paraffin-embedded (FFPE) research samples of several cancer types...
December 2018: Translational Lung Cancer Research
Ignacio Morales-Orue, Rodolfo Chicas-Sett, Pedro C Lara
Over the last decade, immunotherapy has emerged as a hopeful alternative in cancer therapy. Different drugs are used to stimulate the immune system and block negative immune regulatory pathways, known as "immune checkpoint inhibitors (ICI)". Although clinical studies have reported efficacy and safety with the use of ICI, only a small group of patients have obtained a clinical benefit. Because of this, immunomodulation based on immunogenic cell death produced by radiotherapy (RT) has been well positioned as an alternative to increase the clinical effect on the primary neoplasm, but also in distant tumours, a phenomenon known as the "abscopal effect"...
January 2019: Reports of Practical Oncology and Radiotherapy
Takashi Nakamura
The appearance of immune checkpoint inhibitors has been a major turning point in cancer therapy. The success of immune checkpoint therapy has revolutionized the field of cancer therapy, and immunotherapy has joined the cancer treatment ranks as a pillar. To induce effective anti-tumor immune responses, it is necessary both to enhance the activity of immune cells and to block immune suppression by tumor cells. Carrier type drug delivery systems based on nanobiotechnology (nano DDS) represent a potentially useful technology for efficiently achieving both: enhancement of the activity of immune cells and blocking immune suppression...
2018: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
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