Yuta Ando, Chelsea Mariano, Keyue Shen
Tumor immunotherapy is rapidly evolving as one of the major pillars of cancer treatment. Cell-based immunotherapies, which utilize patient's own immune cells to eliminate cancer cells, have shown great promise in treating a range of malignancies, especially those of hematopoietic origins. However, their performance on a broader spectrum of solid tumor types still fall short of expectations in the clinical stage despite of the promising preclinical assessments. In this review, we briefly introduce cell-based immunotherapies and the inhibitory mechanisms in tumor microenvironments that may have contributed to this discrepancy...
April 12, 2021: Acta Biomaterialia
Jennifer A Harbottle
Engineered immune cell therapy is revolutionising the field of cancer therapeutics. US Food and Drug Administration (FDA) approval of two chimeric antigen receptor (CAR)-T cell products for the treatment of haematological malignancies has paved the way for individualised cancer treatment. However, multiple genetic edits will be required to improve the efficacy of CAR-T cell therapies if they are to treat refractory malignancies successfully, particularly solid tumours. Off-target effects of CRISPR-Cas9-mediated multiplex editing are likely to hinder its safety and application in the clinic...
April 12, 2021: Drug Discovery Today
Ester Gangoso, Benjamin Southgate, Leanne Bradley, Stefanie Rus, Felipe Galvez-Cancino, Niamh McGivern, Esra Güç, Chantriolnt-Andreas Kapourani, Adam Byron, Kirsty M Ferguson, Neza Alfazema, Gillian Morrison, Vivien Grant, Carla Blin, IengFong Sou, Maria Angeles Marques-Torrejon, Lucia Conde, Simona Parrinello, Javier Herrero, Stephan Beck, Sebastian Brandner, Paul M Brennan, Paul Bertone, Jeffrey W Pollard, Sergio A Quezada, Duncan Sproul, Margaret C Frame, Alan Serrels, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Mechanistically, this is not elicited via genetic selection of tumor subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack...
April 9, 2021: Cell
Joo Sang Lee, Nishanth Ulhas Nair, Gal Dinstag, Lesley Chapman, Youngmin Chung, Kun Wang, Sanju Sinha, Hongui Cha, Dasol Kim, Alexander V Schperberg, Ajay Srinivasan, Vladimir Lazar, Eitan Rubin, Sohyun Hwang, Raanan Berger, Tuvik Beker, Ze'ev Ronai, Sridhar Hannenhalli, Mark R Gilbert, Razelle Kurzrock, Se-Hoon Lee, Kenneth Aldape, Eytan Ruppin
Precision oncology has made significant advances, mainly by targeting actionable mutations in cancer driver genes. Aiming to expand treatment opportunities, recent studies have begun to explore the utility of tumor transcriptome to guide patient treatment. Here, we introduce SELECT (synthetic lethality and rescue-mediated precision oncology via the transcriptome), a precision oncology framework harnessing genetic interactions to predict patient response to cancer therapy from the tumor transcriptome. SELECT is tested on a broad collection of 35 published targeted and immunotherapy clinical trials from 10 different cancer types...
April 14, 2021: Cell
Byong H Kang, Noor Momin, Kelly D Moynihan, Murillo Silva, Yingzhong Li, Darrell J Irvine, K Dane Wittrup
Following curative immunotherapy of B16F10 tumors, ~60% of mice develop a strong antibody response against cell-surface tumor antigens. Their antisera confer prophylactic protection against intravenous challenge with B16F10 cells, and also cross-react with syngeneic and allogeneic tumor cell lines MC38, EL.4, 4T1, and CT26. We identified the envelope glycoprotein (env) of a murine endogenous retrovirus (ERV) as the antigen accounting for the majority of this humoral response. A systemically administered anti-env monoclonal antibody cloned from such a response protects against tumor challenge, and prophylactic vaccination against the env protein protects a majority of naive mice from tumor establishment following subcutaneous inoculation with B16F10 cells...
2021: PloS One
Yongneng Zhang, Evangelos D Michelakis
No abstract text is available yet for this article.
April 15, 2021: American Journal of Respiratory and Critical Care Medicine
Kari C Nadeau
No abstract text is available yet for this article.
April 15, 2021: American Journal of Respiratory and Critical Care Medicine
Altan Kara, Aykut Özgür, Sinem Nalbantoğlu, Abdullah Karadağ
Lung cancer is the leading cancer type of death rate. The lung adenocarcinoma subtype is responsible for almost half of the total lung cancer deaths. Despite the improvements in cancer treatment in recent years, lung adenocarcinoma patients' overall survival rate remains poor. Immunetherapy and chemotherapy are two of the most widely used options for the treatment of cancer. Although many cancer types initially respond to these treatments, the development of resistance is inevitable. The rapid development of drug resistance mainly characterizes lung adenocarcinoma...
April 15, 2021: Molecular Biology Reports
Devarati Mitra, Gabriel Ologun, Emily Z Keung, Ryan P Goepfert, Rodabe N Amaria, Merrick I Ross, Jeffrey E Gershenwald, Anthony Lucci, Sarah B Fisher, Michael A Davies, Jeffrey E Lee, Andrew J Bishop, Ahsan S Farooqi, Jennifer Wargo, B Ashleigh Guadagnolo
BACKGROUND: Management of patients with sentinel lymph node (SLN)-positive melanoma has changed dramatically over the last few years such that completion lymph node dissection (CLND) has become uncommon, and many patients receive adjuvant immunotherapy or targeted therapy. This study seeks to characterize patterns and predictors of early recurrence in this setting. PATIENTS AND METHODS: All patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy (SLNB) between 3/2016 and 12/2019 were identified...
April 15, 2021: Annals of Surgical Oncology
Ondrej Uher, Veronika Caisova, Lucie Padoukova, Karolina Kvardova, Kamila Masakova, Radka Lencova, Andrea Frejlachova, Marketa Skalickova, Anna Venhauerova, Adela Chlastakova, Per Hansen, Jindrich Chmelar, Jan Kopecky, Zhengping Zhuang, Karel Pacak, Jan Zenka
Pancreatic adenocarcinoma is one of the leading causes of cancer-related deaths, and its therapy remains a challenge. Our proposed therapeutic approach is based on the intratumoral injections of mannan-BAM, toll-like receptor ligands, and anti-CD40 antibody (thus termed MBTA therapy), and has shown promising results in the elimination of subcutaneous murine melanoma, pheochromocytoma, colon carcinoma, and smaller pancreatic adenocarcinoma (Panc02). Here, we tested the short- and long-term effects of MBTA therapy in established subcutaneous Panc02 tumors two times larger than in previous study and bilateral Panc02 models as well as the roles of CD4+ and CD8+ T lymphocytes in this therapy...
April 15, 2021: Cancer Immunology, Immunotherapy: CII
Padma Kadiyala, Jason V Gregory, Pedro R Lowenstein, Joerg Lahann, Maria G Castro
Glioblastoma is an aggressive brain tumor with poor prognosis. The brain is protected by the blood-brain barrier, which precludes transport of chemotherapeutics. We developed nanoparticles that achieve delivery of small-interfering RNA against Stat3 after systemic administration. Nanoparticles combined with radiation inhibited tumor progression and elicited anti-glioblastoma immunity in mice.
January 31, 2021: Molecular & Cellular Oncology
Daniel Geh, Quentin M Anstee, Helen L Reeves
Due to an increase in the obesity-associated metabolic syndrome of epidemic proportions, nonalcoholic fatty liver disease (NAFLD) is becoming a leading cause of hepatocellular carcinoma (HCC) in western countries. This presents added challenges, as NAFLD-associated HCC tends to present at an advanced stage in older patients with co-morbidities. Their prognosis is generally poor with the benefits of standard therapies less certain. The pathogenesis of NAFLD-associated HCC is multifactorial and not well understood, although the risk of HCC developing undoubtedly increases as NAFLD progresses to steatohepatitis and cirrhosis...
2021: Journal of Hepatocellular Carcinoma
Wenlin Chen, Yuekun Wang, Binghao Zhao, Penghao Liu, Lei Liu, Yu Wang, Wenbin Ma
The optimal treatment of recurrent glioblastoma (GBM) remains controversial. Therefore, our study aimed to compare and rank active therapies in recurrent GBM. We performed a systematic review and a Bayesian network meta-analysis. We obtained a treatment hierarchy using the surface under the cumulative ranking curve and mean ranks. A cluster analysis was conducted to aggregate the separated results of three outcomes. The protocol was registered in PROSPERO (CRD42019146794). A total of 1,667 citations were identified, and 15 eligible articles with 17 treatments remained in the final network meta-analysis...
2021: Frontiers in Oncology
Yannick Van Herck, Asier Antoranz, Madhavi Dipak Andhari, Giorgia Milli, Oliver Bechter, Frederik De Smet, Francesca Maria Bosisio
The state-of-the-art for melanoma treatment has recently witnessed an enormous revolution, evolving from a chemotherapeutic, "one-drug-for-all" approach, to a tailored molecular- and immunological-based approach with the potential to make personalized therapy a reality. Nevertheless, methods still have to improve a lot before these can reliably characterize all the tumoral features that make each patient unique. While the clinical introduction of next-generation sequencing has made it possible to match mutational profiles to specific targeted therapies, improving response rates to immunotherapy will similarly require a deep understanding of the immune microenvironment and the specific contribution of each component in a patient-specific way...
2021: Frontiers in Oncology
Xuehui Huang, Jingmei Pan, Funeng Xu, Binfen Shao, Yi Wang, Xing Guo, Shaobing Zhou
In the past decade, bacteria-based cancer immunotherapy has attracted much attention in the academic circle due to its unique mechanism and abundant applications in triggering the host anti-tumor immunity. One advantage of bacteria lies in their capability in targeting tumors and preferentially colonizing the core area of the tumor. Because bacteria are abundant in pathogen-associated molecular patterns that can effectively activate the immune cells even in the tumor immunosuppressive microenvironment, they are capable of enhancing the specific immune recognition and elimination of tumor cells...
April 2021: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Aidin Lak, Sabrina Disch, Philipp Bender
Iron oxide nanoparticles have tremendous scientific and technological potential in a broad range of technologies, from energy applications to biomedicine. To improve their performance, single-crystalline and defect-free nanoparticles have thus far been aspired. However, in several recent studies, defect-rich nanoparticles outperform their defect-free counterparts in magnetic hyperthermia and magnetic particle imaging (MPI). Here, an overview on the state-of-the-art of design and characterization of defects and resulting spin disorder in magnetic nanoparticles is presented with a focus on iron oxide nanoparticles...
April 2021: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Seong Dong Jeong, Bo-Kyeong Jung, Hyo Min Ahn, DaeYong Lee, JongHoon Ha, Ilkoo Noh, Chae-Ok Yun, Yeu-Chun Kim
Immunogenic cell death (ICD) is distinguished by the release of tumor-associated antigens (TAAs) and danger-associated molecular patterns (DAMPs). This cell death has been studied in the field of cancer immunotherapy due to the ability of ICD to induce antitumor immunity. Herein, endoplasmic reticulum (ER) stress-mediated ICD inducing fluorinated mitochondria-disrupting helical polypeptides (MDHPs) are reported. The fluorination of the polypeptide provides a high helical structure and potent anticancer ability...
April 2021: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
Yeongjoo Kim, Ji Wan Kang, Junho Kang, Eun Jung Kwon, Mihyang Ha, Yoon Kyeong Kim, Hansong Lee, Je-Keun Rhee, Yun Hak Kim
The tumor microenvironment (TME) within mucosal neoplastic tissue in oral cancer (ORCA) is greatly influenced by tumor-infiltrating lymphocytes (TILs). Here, a clustering method was performed using CIBERSORT profiles of ORCA data that were filtered from the publicly accessible data of patients with head and neck cancer in The Cancer Genome Atlas (TCGA) using hierarchical clustering where patients were regrouped into binary risk groups based on the clustering-measuring scores and survival patterns associated with individual groups...
March 29, 2021: Oncoimmunology
Anan Yin, Zhende Shang, Amandine Etcheverry, Yalong He, Marc Aubry, Nan Lu, Yuhe Liu, Jean Mosser, Wei Lin, Xiang Zhang, Yu Dong
The clinical and molecular implications of DNA methylation alterations remain unclear among the majority of glioblastomas (GBMs) without glioma-CpGs island methylator phenotype (G-CIMP); integrative multi-level molecular profiling may provide useful information. Independent cohorts of non-G-CIMP GBMs or IDH wild type (wt) lower-grade gliomas (LGGs) from local and public databases with DNA methylation and gene expression microarray data were included for discovery and validation of a multimarker signature, combined using a RISK score model...
March 29, 2021: Oncoimmunology
Cong Chen, Yan-Mei Gu, Fan Zhang, Zheng-Chao Zhang, Ya-Ting Zhang, Yi-Di He, Ling Wang, Ning Zhou, Fu-Tian Tang, Hong-Jian Liu, Yu-Min Li
Chimeric antigen receptor (CAR) T cell is a promising method in cancer immunotherapy but faces many challenges in solid tumors. One of the major problems was immunosuppression caused by PD-1. In our study, the expression of c-Met in GC was analyzed from TCGA datasets, GC tissues, and cell lines. The c-Met CAR was a second-generation CAR with 4-1BB, cMet-PD1/CD28 CAR was c-Met CAR adding PD1/CD28 chimeric-switch receptor (CSR). In vitro , we measured the changes of different subgroups, phenotypes and PD-1 expression in CAR-T cells...
March 31, 2021: Oncoimmunology
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