Shorouk M El-Sayyad, Mennatallah A Ali, Lamia S Kandil, Ghada M Ragab, Sherihan S Abdelhamid Ibrahim
OBJECTIVE: Rheumatoid arthritis is a progressive inflammatory disease with multiple dysfunctional intracellular signaling pathways that necessitate new approaches for its management. Hence, the study aimed to inspect the ability of the combination therapy of metformin and omega-3 to modulate different signaling pathways and micro RNAs such as (miR-155, miR-146a and miR-34) as new targets in order to mitigate adjuvant-induced arthritis and compare their effect to that of methotrexate. METHODS: Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with metformin (200 mg/kg/day) and/or omega-3 (300 mg/kg/day) or intraperitoneally with methotrexate (2 mg/kg/week) for 4 weeks...
January 13, 2021: International Immunopharmacology
Jinsheng Huang, Zecong Xiao, Yongcheng An, Shisong Han, Wei Wu, Yong Wang, Yu Guo, Xintao Shuai
Although a combination with photodynamic therapy (PDT) is a potential means to improve the immune checkpoint blockade (ICB)-based anticancer immunotherapy, this strategy is subjected to the extremely poor light penetration in melanoma. Herein, we develop a lipid (LP)-based micellar nanocarrier encapsulating sonosensitizer chlorin e6 (Ce6) in the core, conjugating anti-PD-L1 antibody (aPD-L1) to the interlayer through MMP-2-cleavable peptide, and bearing a PEG coating sheddable at low pH value (≈6.5) of tumor microenvironment...
January 4, 2021: Biomaterials
M Rey-Cárdenas, F Guerrero-Ramos, A Gómez de Liaño Lista, A Carretero-González, H Bote, M Herrera-Juárez, L Carril-Ajuria, M Martín-Soberón, J M Sepulveda, E G Billalabeitia, D Castellano, G de Velasco
Urothelial bladder cancer (UC) is the most common malignancy involving the urinary system and represents a significant health problem. Immunotherapy has been used for decades for UC with intravesical bacillus Calmette-Guérin (BCG) set as the standard of care for non-muscle-invasive bladder cancer (NMIBC). The advent of immune checkpoint inhibitors (ICIs) has completely transformed the treatment landscape of bladder cancer enabling to expand the treatment strategies. Novel ICIs have successfully shown improved outcomes on metastatic disease to such an extent that the standard of care paradigm has changed leading to the development of different trials with the aim of determining whether ICIs may have a role in early disease...
January 5, 2021: Cancer Treatment Reviews
Fatemeh Moadab, Hossein Khorramdelazad, Mitra Abbasifard
Evidence suggests that uncontrolled immune system responses and their components play a significant role in developing rheumatoid arthritis (RA), which is considered an autoimmune disease (AD). Among immune system mediators, cytokines and chemokines are involved in numerous physiological and pathological processes. CCL2 or monocyte chemoattractant protein-1 (MCP-1) is known as a CC chemokine that can induce the locomotion and recruitment of monocytes and macrophages to the site of injury. When CCL2 binds to its receptors, the most important of which is CCR2, various signaling pathways are triggered, eventually leading to various immunological events such as inflammation...
January 13, 2021: Life Sciences
Tomonari Kinoshita, Mohammad Abu Sayem, Tomonori Yaguchi, Budiman Kharma, Kenji Morii, Daiki Kato, Shigeki Ohta, Yukihiko Mashima, Hisao Asamura, Yutaka Kawakami
Modulation of the immunosuppressive tumor microenvironment (TME) is essential for enhancing the anti-tumor effects of immune checkpoint inhibitors (ICIs). Adhesion molecules and enzymes such as vascular adhesion protein-1 (VAP-1), which are expressed in some cancers and tumor vascular endothelial cells, may be involved in the generation of an immunosuppressive TME. In this study, the role of VAP-1 in TME was investigated in two murine colon cancer models and human cancer cells. Intraperitoneal administration of the VAP-1-specific inhibitor U-V296 inhibited murine tumor growth by enhancing IFN-γ-producing tumor antigen-specific CD8+ T cells...
January 16, 2021: Cancer Science
Naama Epstein Rigbi, Naama Schwartz, Michael R Goldberg, Michael B Levy, Liat Nachshon, Arnon Elizur
BACKGROUND: The start of oral immunotherapy (OIT) for food allergy is a critical period in the treatment process, with a potential to influence patient quality of life (QOL) and subsequently treatment outcome. The association of medical clowning with QOL at OIT initiation was examined. METHODS: Children aged 4-12 years supported by a medical clown (MC) during the induction week of OIT for food allergy were studied. Children in the same age range starting OIT without the support of a MC served as controls...
January 16, 2021: Pediatric Allergy and Immunology
Fengyi Hou, Zhiyuan Pan, Ruifu Yang, Fachao Zhi, Yujing Bi
Programmed cell death protein-1/programmed cell death-ligand 1 and cytotoxic T-lymphocyte antigen-4 are two immune checkpoint inhibitors (ICIs), exhibiting significant antitumor effects on multiple types of cancers in clinical practice. However, only some patients respond to ICI agents, which limits their widespread application. Recent findings revealed that the gut microbiota is relevant to host health through the modulation of host physical and immune functions. Therefore, the modulation of gut microbiota to achieve the desired taxa may be a potential strategy to improve the efficacy of immunotherapies...
January 16, 2021: Journal of Cellular Physiology
Aaron D Stevens, Timothy N J Bullock
Dendritic cells are potently activated by the synergistic action of CD40 stimulation in conjunction with signaling through toll like receptors, subsequently priming T cells. Cancer vaccines targeting the activation of dendritic cells in this manner show promise in murine models and are being developed for human patients. While the efficacy of vaccines based on CD40 and toll like receptor stimulation has been established, further investigation is needed to understand the mechanism of tumor control and how vaccination alters tumor infiltrating immune cells...
January 16, 2021: Cancer Immunology, Immunotherapy: CII
Claudia Canzonetta, Andrea Pelosi, Sabina Di Matteo, Irene Veneziani, Nicola Tumino, Paola Vacca, Enrico Munari, Marco Pezzullo, Charles Theuer, Rita De Vito, Vito Pistoia, Luigi Tomao, Franco Locatelli, Lorenzo Moretta, Ignazio Caruana, Bruno Azzarone
BACKGROUND: Neuroblastoma (NB) is the most common, extracranial childhood solid tumor arising from neural crest progenitor cells and is a primary cause of death in pediatric patients. In solid tumors, stromal elements recruited or generated by the cancer cells favor the development of an immune-suppressive microenvironment. Herein, we investigated in NB cell lines and in NB biopsies, the presence of cancer cells with mesenchymal phenotype and determined the immune-suppressive properties of these tumor cells on natural killer (NK) cells...
January 2021: Journal for Immunotherapy of Cancer
Moran Yang, Jiaqi Lu, Guodong Zhang, Yiying Wang, Mengdi He, Qing Xu, Congjian Xu, Haiou Liu
BACKGROUND: Most patients with high-grade serous ovarian cancer (HGSC) lack an effective response to immune checkpoint blockade, highlighting the need for more knowledge about what is required for successful treatment. As follicular cytotoxic CXCR5+ CD8+ T cells are maintained by reinvigoration by immune checkpoint blockade in tumors, we attempted to reveal the relationship between CXCR5+ CD8+ T cells and the tumor microenvironment to predict immunotherapy responses in HGSC. METHODS: 264 patients with HGSC from two cohorts and 340 HGSC cases from The Cancer Genome Atlas cohort were enrolled...
January 2021: Journal for Immunotherapy of Cancer
Sheera R Rosenbaum, Nicole A Wilski, Andrew E Aplin
Unleashing the immune system with immune checkpoint inhibitors (ICI) has significantly improved overall survival for subsets of patients with stage III/IV cancer. However, many tumors are nonresponsive to ICIs, in part due to a lack of tumor-infiltrating lymphocytes (TIL). Converting these immune "cold" tumors to "hot" tumors that are thus more likely to respond to ICIs is a major obstacle for cancer treatment. Triggering inflammatory forms of cell death, such as necroptosis and pyroptosis, may alter the tumor immune microenvironment and the influx of TILs...
January 15, 2021: Cancer Discovery
Shuchi Gulati, Ramya Muddasani, Paulo Gustavo Bergerot, Sumanta K Pal
As the novel severe acute respiratory syndrome coronavirus-2 related pandemic - Corona Virus Disease 2019 (COVID-19) has emerged, decision making in the context of cancer treatment has become more complex. The apprehension of using drugs that could adversely affect infected patients, the risk of not using life-saving treatments and the complexities related to the type of cancer itself, all must be taken into consideration before proceeding with treatment. Data from large registries such as COVID-19 and Cancer Consortium, Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) and NCI COVID-19 in Cancer Patients Study will hopefully provide granularity on the outcomes of patients with cancer who are infected with COVID-19...
December 26, 2020: Urologic Oncology
Lucía Trilla-Fuertes, Ismael Ghanem, Angelo Gámez-Pozo, Joan Maurel, Laura G-Pastrián, Marta Mendiola, Cristina Peña, Rocío López-Vacas, Guillermo Prado-Vázquez, Elena López-Camacho, Andrea Zapater-Moros, Victoria Heredia, Miriam Cuatrecasas, Pilar García-Alfonso, Jaume Capdevila, Carles Conill, Rocío García-Carbonero, Ricardo Ramos-Ruiz, Claudia Fortes, Carlos Llorens, Paolo Nanni, Juan Ángel Fresno Vara, Jaime Feliu
Anal squamous cell carcinoma is a rare tumor. Chemo-radiotherapy yields a 50% 3-year relapse-free survival rate in advanced anal cancer, so improved predictive markers and therapeutic options are needed. High-throughput proteomics and whole-exome sequencing were performed in 46 paraffin samples from anal squamous cell carcinoma patients. Hierarchical clustering was used to establish groups de novo. Then, probabilistic graphical models were used to study the differences between groups of patients at the biological process level...
April 2020: Molecular & Cellular Proteomics: MCP
Michael Ghosh, Marion Gauger, Ana Marcu, Annika Nelde, Monika Denk, Heiko Schuster, Hans-Georg Rammensee, Stefan Stevanović
For more than two decades naturally presented, human leukocyte antigen (HLA)-restricted peptides (immunopeptidome) have been eluted and sequenced using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since, identified disease-associated HLA ligands have been characterized and evaluated as potential active substances. Treatments based on HLA-presented peptides have shown promising results in clinical application as personalized T cell-based immunotherapy. Peptide vaccination cocktails are produced as investigational medicinal products under GMP conditions...
March 2020: Molecular & Cellular Proteomics: MCP
Nataly Mancette Rijensky, Netta R Blondheim Shraga, Eilon Barnea, Nir Peled, Eli Rosenbaum, Aron Popovtzer, Solomon M Stemmer, Alejandro Livoff, Mark Shlapobersky, Neta Moskovits, Dafna Perry, Eitan Rubin, Itzhak Haviv, Arie Admon
Personalized cancer immunotherapy targeting patient-specific cancer/testis antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. Although significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis...
August 2020: Molecular & Cellular Proteomics: MCP
Mariko Ishibashi, Rimpei Morita, Hideto Tamura
The signaling lymphocytic activation molecule (SLAM) family receptors are expressed on various immune cells and malignant plasma cells in multiple myeloma (MM) patients. In immune cells, most SLAM family molecules bind to themselves to transmit co-stimulatory signals through the recruiting adaptor proteins SLAM-associated protein (SAP) or Ewing's sarcoma-associated transcript 2 (EAT-2), which target immunoreceptor tyrosine-based switch motifs in the cytoplasmic regions of the receptors. Notably, SLAMF2, SLAMF3, SLAMF6, and SLAMF7 are strongly and constitutively expressed on MM cells that do not express the adaptor proteins SAP and EAT-2...
January 13, 2021: Cancers
Saman Fouladirad, Horacio Bach
The Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, was first reported in December 2019 in Wuhan, Hubei province, China. This virus has led to 61.8 million cases worldwide being reported as of December 1st, 2020. Currently, there are no definite approved therapies endorsed by the World Health Organization for COVID-19, focusing only on supportive care. Treatment centers around symptom management, including oxygen therapy or invasive mechanical ventilation. Immunotherapy has the potential to play a role in the treatment of SARS-CoV-2...
January 13, 2021: Microorganisms
Nai-Jung Chiang, Li-Tzong Chen, Yan-Shen Shan, Chun-Nan Yeh, Ming-Huang Chen
Biliary tract cancer (BTC) compromises a heterogenous group of tumors with poor prognoses. Curative surgery remains the first choice for localized disease; however, most BTC patients have had unresectable or metastatic disease. The gold standard therapy for these patients is chemotherapy with gemcitabine and cisplatin. There are no consensus guidelines for standard treatment in a second-line setting, although the data of the ABC-06 trial showed a slight survival benefit from oxaliplatin and 5-fluorouracil combination chemotherapy...
January 13, 2021: Biomolecules
Tamiem Adam, Therese M Becker, Wei Chua, Victoria Bray, Tara L Roberts
Immune checkpoint inhibitors (ICIs) are being increasingly utilised in a variety of advanced malignancies. Despite promising outcomes in certain patients, the majority will not derive benefit and are at risk of potentially serious immune-related adverse events (irAEs). The development of predictive biomarkers is therefore critical to personalise treatments and improve outcomes. A number of biomarkers have shown promising results, including from tumour (programmed cell death ligand 1 (PD-L1), tumour mutational burden (TMB), stimulator of interferon genes (STING) and apoptosis-associated speck-like protein containing a CARD (ASC)), from blood (peripheral blood mononuclear cells (PBMCs), circulating tumour DNA (ctDNA), exosomes, cytokines and metal chelators) and finally the microbiome...
January 13, 2021: Cancers
Fabio Morandi, Federica Sabatini, Marina Podestà, Irma Airoldi
Neuroblastoma is the most common extracranial pediatric solid tumor with a heterogeneous clinical course, ranging from spontaneous regression to metastatic disease and death, irrespective of intensive chemotherapeutic regimen. On the basis of several parameters, children affected by neuroblastoma are stratified into low, intermediate and high risk. At present, more than 50% of high-risk patients with metastatic spread display an overall poor long-term outcome also complicated by devastating long-term morbidities...
January 13, 2021: Vaccines
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