Ligong Lu, Jun Jiang, Meixiao Zhan, Hui Zhang, Qian-Ting Wang, Sheng-Nan Sun, Xiao-Kai Guo, Hua Yin, Yadong Wei, Shi-You Li, Jun O Liu, Yong Li, You-Wen He
There are few treatment options for advanced-stage hepatocellular carcinoma (HCC). Targeting tumor-associated antigens (TAAs) for HCC immunotherapy has been tested clinically for many years with limited success. Recent advances in applying mutated tumor-specific neoantigens as immunotherapeutic targets raise hope that this class of antigens may be used in HCC treatment. Accordingly, multiple clinical trials have been initiated to test this concept. However, recent findings demonstrate that mutated neoantigens are rarely detected while unmutated antigens derived from TAAs are represented in the HLA ligandomes of HCC patients, suggesting a requirement to target TAAs for HCC immunotherapy...
August 7, 2020: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Anna S Smagina, Sergey V Kulemzin, Gaukhar M Yusubalieva, Anna G Kedrova, Andrey E Sanzharov, Yurii V Ivanov, Darya A Matvienko, Vladimir A Kalsin, Andrey A Gorchakov, Vladimir P Baklaushev, Aleksandr V Taranin
Immunotherapy based on adoptive transfer of genetically engineered T- and NK-cells is an area of active ongoing research, and has proven highly efficacious for patients with certain B-cell malignancies. Use of NK cells and NK cell lines as carriers of chimeric antigen receptors (CARs) appears particularly promising, as this opens an opportunity for moving the therapy from autologous to the allogeneic (universal) format. This "off-the-shelf" approach is thought to significantly reduce the price of the treatment and make it available to many more patients in need...
August 7, 2020: Biotechnology and Applied Biochemistry
Jing H Wang
The question as to why some hosts can eradicate their tumors while others succumb to tumor-progression remains unanswered. Here, a provocative concept is proposed that intrinsic differences in the T cell receptor (TCR) repertoire of individuals may influence the outcome of anti-tumor immunity by affecting the frequency and/or variety of tumor-reactive CD8 and/or CD4 tumor-infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, "a hole in the TCR repertoire" might exist...
August 7, 2020: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
Nicola J Mason
Approximately 800 people are diagnosed with osteosarcoma (OSA) per year in the USA. Although 70% of patients with localized OSA are cured with multiagent chemotherapy and surgical resection, the prognosis for patients with metastatic or relapsed disease is guarded. The small number of patients diagnosed annually contributes to an incomplete understanding of disease pathogenesis, and challenges in performing appropriately powered clinical trials and detecting correlative biomarkers of response. While mouse models of OSA are becoming increasingly sophisticated, they generally fail to accurately recapitulate tumor heterogeneity, tumor microenvironment (TME), systemic immune dysfunction, and the clinical features of tumor recurrence, metastases, and chemoresistance, which influence outcome...
2020: Advances in Experimental Medicine and Biology
Hillary G Pratt, E Markel Justin, Brock A Lindsey
Osteosarcoma, the most common malignant bone tumor in children and adolescents, remains a complicated disease to treat; no new treatments have been developed in more than three decades. Due to the importance of the immune system in osteosarcoma disease progression, immunotherapeutic strategies have been explored to potentially improve long-term survival. However, most immunotherapeutics have not reached the level of success hoped would occur in this disease. Understanding the immune system in osteosarcoma will be key to optimizing treatments and improving patient outcomes...
2020: Advances in Experimental Medicine and Biology
Xiaolong Wu, Xiangyu Gao, Xiaofang Xing, Xianzi Wen, Ziyu Li, Jiafu Ji
BACKGROUND: Immunogenic chemotherapy promotes antitumor immune response in the tumor microenvironment (TME). In gastric cancer, the effect of a preexisting T-cell-inflamed TME on the efficacy of adjuvant chemotherapy (ACT) is unclear. The purpose of the present study was to evaluate the benefits of ACT in T-cell-inflamed gastric cancer. METHODS: Three cohorts (n = 267, 300, and 198) of gastric cancer patients who underwent gastrectomy with or without ACT were included in this study...
August 7, 2020: Annals of Surgical Oncology
Carly Bess Williams, Caroline A Nebhan, Jinming Yang, Lauren S Starnes, Chi Yan, Anna E Vilgelm, Sheau-Chiann Chen, Gregory Dan Ayers, Vandana Abramson, Ingrid A Mayer, Ann Richmond
PURPOSE: Patients with localized breast cancer have a 5-year survival rate > 99% compared to patients with metastatic breast cancer (MBC) that have a 5-year survival rate of ~ 27%. Unregulated PI3K/AKT signaling is a common characteristic of MBC, making it a desirable therapeutic target for tumors with activating mutations in this pathway. Interestingly, inhibition of the PI3K/AKT pathway can affect signaling in immune cells, which could potentially alter the immune phenotype of patients undergoing therapy with these drugs...
August 7, 2020: Breast Cancer Research and Treatment
Gianluca Perego, Paolo Barzaghi, Ivano Vavassori, Fausto Petrelli
First-line treatment for metastatic clear-cell renal cell carcinoma patients with intermediate and poor-risk features consists of a combination of immune checkpoint inhibitors (e.g., nivolumab + ipilimumab) or immunotherapy with an anti-vascular endothelial growth factor receptor (VEGFR) drug (e.g., axitinib). The subsequent line of therapy should be determined on the basis of previous treatments and approved drugs available, based on the results of randomized clinical trials. Unfortunately, no phase 3 trial has compared the safety and efficacy of drugs after immunotherapy; thus, drug choice is more empirical than evidence-based...
August 7, 2020: Medical Oncology
Wilson Alobuia, Andrea Gillis, Electron Kebebew
Anaplastic thyroid cancer (ATC) is a rare but very aggressive form of undifferentiated thyroid cancer. Due to its rapid rate of progression and invasive nature, ATC poses significant risks of morbidity and mortality. The cornerstone in the management of ATC remains a prompt diagnosis of the disease and timely management of complications depending on the stage of disease. Surgery continues to offer a higher chance of a cure, although not all patients are candidates for surgical management. Patients with advanced disease may be considered for palliative surgery to reduce morbidity and complications from advanced disease...
August 7, 2020: Current Treatment Options in Oncology
F Bootz, A Franzen
Surgical therapy, regardless of the procedure, remains of great importance for today's treatment of oropharyngeal carcinomas, despite advances in radiation and immunotherapy. The individual treatment plan should be defined in discussion with the patient and in an interdisciplinary tumor conference, taking into account the likelihood of achieving of tumor-free resection margins and an acceptable postoperative quality of life. With regard to conventional and possibly also open surgical procedures, a good overview of the surgical site-particularly in the case of more extensive carcinomas and challenging patient anatomy-and simplified reconstructability of the defect region are decisive aspects...
August 7, 2020: HNO
Fang Yang, Svetomir N Markovic, Julian R Molina, Thorvardur R Halfdanarson, Lance C Pagliaro, Ashish V Chintakuntlawar, Rutian Li, Jia Wei, Lifeng Wang, Baorui Liu, Grzegorz S Nowakowski, Michael L Wang, Yucai Wang
Importance: Sex, age, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) may affect immune response. However, the association of these factors with the survival benefit of cancer immunotherapy with immune checkpoint inhibitors (ICIs) remains unclear. Objective: To assess the potential sex, age, and ECOG PS differences of immunotherapy survival benefit in patients with advanced cancer. Data Sources: PubMed, Web of Science, Embase, and Scopus were searched from inception to August 31, 2019...
August 3, 2020: JAMA Network Open
Xiuxiu Yao, Baochan Yang, Shan Wang, Zhichao Dai, Dongsheng Zhang, Xiuwen Zheng, Qingyun Liu
A new multi-modal therapy agent, FePt/BP-PEI-FA nanoplatform, with FePt nanoparticles (FePt NPs) loaded onto ultrathin black phosphorus nanosheets (BPNs), has been constructed to enhance synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemodynamic therapy (CDT) that target primary tumors. In this work, BPNs exhibit excellent photothermal and photodynamic behaviors under different wavelength laser irradiation. After polyethylenimine (PEI) modification, FePt NPs with sizes of 3-4 nm are uniformly attached onto the surface of modified BPNs via electrostatic adsorption...
August 7, 2020: Journal of Materials Chemistry. B, Materials for Biology and Medicine
Chimaobi Anugwom, Thomas Leventhal
Cancer treatment has taken giant strides in recent years with the advent of immunotherapy, including checkpoint inhibitors. The use of these medications in liver transplant recipients has been debated, and the added effect of previous hepatitis C infection on the immune system in this setting, is poorly understood. We present a case of cholestatic hepatitis after the treatment of recurrent hepatocellular carcinoma with nivolumab in the post-transplant period. Understanding the pathophysiology is relevant to improving the management of this type of liver injury and expanding our knowledge of programmed death-1 inhibitors in liver transplant recipients...
July 2020: ACG Case Reports Journal
Andreas Saltos, Michael Shafique, Alberto Chiappori
Small-cell lung cancer (SCLC) accounts for 13-15% of all new lung cancer cases in the US. The tumor has a tendency to disseminate early resulting in 80-85% of patients being diagnosed with extensive disease (ES-SCLC). Chemotherapy has provided SCLC patients considerable survival benefits over the past three decades. Nonetheless, most patients relapse and rarely survive beyond 2 years. Despite consistent overall response rates of ≥50%, until recently, median survival times and 2-year survivals only ranged between 7-10 months and 10-20%, respectively...
2020: Frontiers in Oncology
Parnia Forouzan, Philip R Cohen
Alopecia areata is a non-scarring hair loss that commonly presents on the scalp. In men, when this condition results in facial hair loss on the cheek, jaw, and neck, it is referred to as beard alopecia areata. Beard alopecia areata can be associated with autoimmune conditions, such as diabetes mellitus, thyroid disorders, and vitiligo. A 28-year-old man presented with a five-month history of facial hair loss; his condition was diagnosed as beard alopecia areata after clinical examination. Treatment with twice daily topical 0...
July 31, 2020: Curēus
Raman J Sohal, Sandeep Sohal, Ali Wazir, Sam Benjamin
Mucosal melanoma is a rare variant of melanoma representing around 1% of total cases of melanoma diagnosed. The usual sites of mucosal involvement are the sino-nasal passages, the oral cavity, and less commonly the upper gastrointestinal (GI) tract. It also has been reported to occur in vulvovaginal and anorectal mucosa.  We present a rare case of mucosal melanoma that presented as recurrent epistaxis, headache, and sinus pressure. CT maxillofacial imaging revealed a large mass right nasal cavity. This was biopsied by ENT and shown to be mucosal melanoma...
July 30, 2020: Curēus
Hao Wang, Chao Yan, Hong Ye
Cervical cancer (CC) is the fourth ranking gynaecologic tumour in women worldwide, with respect to both incidence and mortality. MUC16 is one of the most frequently mutated genes, which functions as a tumour marker in CC. In the present study, mutation, clinical and RNA-Seq data collected from The Cancer Genome Atlas database were used to investigate the association between MUC16 mutation, immune response and clinical prognosis in CC. mRNA expression levels from the TCGA datasets and the results from the present study demonstrated that MUC16 was overexpressed in CC samples; however, there was no difference between mutant and wild-type CC samples...
August 2020: Experimental and Therapeutic Medicine
Yang Kong, Zi-Chao Feng, Yu-Lin Zhang, Xiao-Fei Liu, Yuan Ma, Zhi-Min Zhao, Bin Huang, An-Jing Chen, Di Zhang, Frits Thorsen, Jian Wang, Ning Yang, Xin-Gang Li
Background: The tumor microenvironment (TME) of human glioblastoma (GBM) exhibits considerable immune cell infiltration, and such cell types have been shown to be widely involved in the development of GBM. Here, weighted correlation network analysis (WGCNA) was performed on publicly available datasets to identify immune-related molecules that may contribute to the progression of GBM and thus be exploited as potential therapeutic targets. Methods: WGCNA was used to identify highly correlated gene clusters in Chinese Glioma Genome Atlas glioma dataset...
2020: Frontiers in Immunology
Alessio Romerio, Francesco Peri
Toll-Like Receptor 4 (TLR4) is one of the receptors of innate immunity. It is activated by Pathogen- and Damage-Associated Molecular Patterns (PAMPs and DAMPs) and triggers pro-inflammatory responses that belong to the repertoire of innate immune responses, consequently protecting against infectious challenges and boosting adaptive immunity. Mild TLR4 stimulation by non-toxic molecules resembling its natural agonist (lipid A) provided efficient vaccine adjuvants. The non-toxic TLR4 agonist monophosphoryl lipid A (MPLA) has been approved for clinical use...
2020: Frontiers in Immunology
Yi-Te Huang, Ya-Ping Chen, Wen-Chih Lin, Wu-Chou Su, Yuan-Ting Sun
The development of immune checkpoint inhibitors (ICIs) has been a major breakthrough in cancer immunotherapy. The increasing use of ICIs has led to the discovery of a broad spectrum of immune-related adverse events (irAEs). Immune-related myasthenia gravis (irMG) is a rare but life-threatening irAE. In this review, the clinical presentations of irMG are described and the risk of irMG-related mortality is examined using information from relevant studies. In 47 reported cases of irMG with clear causes of mortality, irMG appeared to be a distinct category of neuromuscular disorders and differed from classical MG in terms of its demographic patient characteristics, pathogenesis, serology profile, response to treatment, associated complications, and prognosis...
2020: Frontiers in Neurology
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