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Immune based cancer therapy

Lan Huang, Huaxi Xu, Guangyong Peng
Cellular energy metabolism not only promotes tumor cell growth and metastasis but also directs immune cell survival, proliferation and the ability to perform specific and functional immune responses within the tumor microenvironment. A better understanding of the molecular regulation of metabolism in different cell components in the tumor-suppressive microenvironment is critical for the development of effective strategies for human cancer treatments. Toll-like receptors (TLRs) have recently been recognized as critical factors involved in tumor pathogenesis, regulating both tumor cells and tumor-infiltrating innate and adaptive immune cells...
March 19, 2018: Cellular & Molecular Immunology
Lijuan Wang, Yanchun Quan, Yongfang Yue, Xueyuan Heng, Fengyuan Che
Interleukin (IL)-37, a new IL-1 family member, has received increasing attention in recent years. In the past decade, it has been determined that IL-37 is expressed in various normal cells and tissues and is regulated by inflammatory stimuli and pro-cytokines via different signal transduction pathways. Recently, it has been found that IL-37 is expressed in a variety of cancers, chronic inflammatory and autoimmune disorders, and exerts anti-inflammatory effects. Moreover, a growing body of literature demonstrates that IL-37 plays a vital role in inhibiting both innate and adaptive immune responses as well as inflammatory reactions...
April 2018: Oncology Letters
A Boussommier-Calleja, Y Atiyas, K Haase, M Headley, C Lewis, R D Kamm
Metastasis is the leading cause of cancer-related deaths. Recent developments in cancer immunotherapy have shown exciting therapeutic promise for metastatic patients. While most therapies target T cells, other immune cells, such as monocytes, hold great promise for therapeutic intervention. In our study, we provide primary evidence of direct engagement between human monocytes and tumor cells in a 3D vascularized microfluidic model. We first characterize the novel application of our model to investigate and visualize at high resolution the evolution of monocytes as they migrate from the intravascular to the extravascular micro-environment...
March 5, 2018: Biomaterials
Aurélien Gobert, Marianne Veyri, Isabelle Poizot-Martin, Armelle Lavolé, Caroline Solas, Romain Paliche, Christine Katlama, Dominique Costagliola, Jean-Philippe Spano
Since the era of combined antiretroviral therapy, life expectancy of people living with HIV has been improved and is associated with a change in causes of death. Cancer, both AIDS-defining or non-AIDS-defining cancers, has become the leading cause of death in people living with HIV associated with an increase in the incidence of some cancers compared to the general population. Epidemiology and the identification of risk factors is a crucial issue, particularly to determine the most appropriate prevention and screening strategies in this population...
March 13, 2018: Bulletin du Cancer
Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Marina Chiara Garassino, Byoung-Chul Cho, Joo-Hang Kim, Julien Mazières, Johan Vansteenkiste, Hervé Lena, Jesus Corral Jaime, Jhanelle E Gray, John Powderly, Christos Chouaid, Paolo Bidoli, Paul Wheatley-Price, Keunchil Park, Ross A Soo, Yifan Huang, Catherine Wadsworth, Phillip A Dennis, Naiyer A Rizvi
BACKGROUND: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR-/ALK-), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1...
March 12, 2018: Lancet Oncology
Benjamin L Solomon, Ignacio Garrido-Laguna
The advent of immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4) has resulted in unprecedented long-term remissions of unresectable cancers. The efficacy of checkpoint inhibitors was recently demonstrated in gastrointestinal malignancies with mismatch repair deficiencies (dMMR). Pembrolizumab became the first tissue-agnostic US FDA-approved drug based on the presence of the predictive biomarker dMMR. In addition, the FDA in 2017 approved pembrolizumab for PD-L1-positive advanced gastric cancer in third-line and second-line hepatocellular therapy...
March 15, 2018: Future Oncology
Alejo Rodriguez-Vida, Joaquim Bellmunt
Metastatic urothelial carcinoma (UC) remains an aggressive disease associated with limited treatment options and a reduced survival. In spite of this, the first-line treatment based on platinum-based combinations has remained virtually unchanged for the last 20-30 years. Similarly, before the advent of the immune checkpoint inhibitors, there were no FDA-approved drugs for second-line therapy. In the last few years, impressive signs of anti-tumor activity have been reported with several immunotherapy agents targeting the programmed cell death-1 (PD-1) pathway...
March 14, 2018: Expert Review of Anticancer Therapy
Mei Zhang, Julian A Kim, Alex Yee-Chen Huang
Immunotherapy is revolutionizing cancer treatment. Recent clinical success with immune checkpoint inhibitors, chimeric antigen receptor T-cell therapy, and adoptive immune cellular therapies has generated excitement and new hopes for patients and investigators. However, clinically efficacious responses to cancer immunotherapy occur only in a minority of patients. One reason is the tumor microenvironment (TME), which potently inhibits the generation and delivery of optimal antitumor immune responses. As our understanding of TME continues to grow, strategies are being developed to change the TME toward one that augments the emergence of strong antitumor immunity...
2018: Frontiers in Immunology
Johanna M Gostner, Eva Obermayr, Ioana E Braicu, Nicole Concin, Sven Mahner, Adriaan Vanderstichele, Jalid Sehouli, Ignace Vergote, Dietmar Fuchs, Robert Zeillinger
OBJECTIVE: Circulating tumor cells (CTCs) may represent a chronic stimulus for the immune system. In the present study we investigated the potential association of CTCs, the immune activation marker neopterin, and the ratio of kynurenine to tryptophan (Kyn/Trp) as a measure for tryptophan breakdown. METHODS: Neopterin, tryptophan and kynurenine levels were measured in plasma samples from patients with benign gynecological diseases (n=65) and with primary advanced epithelial ovarian cancer (EOC) at diagnosis (n=216) and six months after adjuvant platinum-based chemotherapy (n=45) by an enzyme-linked immunosorbent assay and high performance liquid chromatography...
March 9, 2018: Gynecologic Oncology
Soumaya Kouidhi, Farhat Ben Ayed, Amel Benammar Elgaaied
Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains a major challenge for more effective antitumor immunity. There is a growing evidence that the TME supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the antitumor immune response and tumor progression...
2018: Frontiers in Immunology
Darya Alizadeh, Ethan E White, Teresa C Sanchez, Shunan Liu, Leying Zhang, Behnam Badie, Jacob M Berlin
Even when treated with aggressive current therapies, patients with glioblastoma usually survive less than two years and exhibit a high rate of recurrence. CpG is an oligonucleotide that activates the innate immune system via TLR9 activation. Injection of CpG into glioblastoma tumors showed promise as an immunotherapy in mouse models but proved disappointing in human trials. One aspect of glioma that is not addressed by CpG therapy alone is the highly invasive nature of glioma cells, which is associated with resistance to radiation and chemotherapy...
March 10, 2018: Bioconjugate Chemistry
Mengdi Yang, Yi Sun, Jing Sun, Zhiyu Wang, Yiyi Zhou, Guangyu Yao, Yifeng Gu, Huizhen Zhang, Hui Zhao
Despite recent advances in targeted and immune-based therapies, the poor prognosis of lung adenocarcinoma (LUAD) with bone metastasis (BM) remains a challenge. First, two-dimensional gel electrophoresis (2-DE) was used to identify proteins that were differentially expressed in LUAD with BM, and then matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify these proteins. Second, the Cancer Genome Atlas (TCGA) was used to identify mutations in these differentially expressed proteins and Kaplan-Meier plotter (KM Plotter) was used to generate survival curves for the analyzed cases...
March 9, 2018: Cancer Medicine
Yong-Seok Kim, Jae-Sung Ahn, Semi Kim, Hyun-Jin Kim, Shin-Hee Kim, Ju-Seop Kang
Exosomes are membranous vesicles of 30-150 nm in diameter that are derived from the exocytosis of the intraluminal vesicles of many cell types including immune cells, stem cells, cardiovascular cells and tumor cells. Exosomes participate in intercellular communication by delivering their contents to recipient cells, with or without direct contact between cells, and thereby influence physiological and pathological processes. They are present in various body fluids and contain proteins, nucleic acids, lipids, and microRNAs that can be transported to surrounding cells...
March 2018: Korean Journal of Physiology & Pharmacology
Madelon Q Wentink, Henk M W Verheul, Arjan W Griffioen, Kenneth A Schafer, Susan McPherson, Richard J Early, Hans J van der Vliet, Tanja D de Gruijl
INTRODUCTION: Vascular endothelial growth factor (VEGF) is pivotal in tumor angiogenesis and therapies targeting the VEGF axis are widely used in the clinic for the treatment of cancer. We have developed a therapeutic vaccine targeting human (h)VEGF165 . hVEGF26-104 /RFASE is based on the truncated protein hVEGF26-104 as antigen formulated in an oil-in-water emulsion containing the sulpholipopolysaccharide RFASE as adjuvant. Here we describe the toxicity and immunogenicity of this therapeutic vaccine in cynomolgus monkeys...
March 5, 2018: Vaccine
Mark A Samaan, Polychronis Pavlidis, Sophie Papa, Nick Powell, Peter M Irving
Immune checkpoint inhibitor therapies are a novel group of monoclonal antibodies with proven effectiveness in a wide range of malignancies, including melanoma, renal cell carcinoma, non-small-cell lung cancer, urothelial carcinoma and Hodgkin lymphoma. Their use in a range of other indications, such as gastrointestinal and head and neck cancer, is currently under investigation. The number of agents included in this drug group is increasing, as is their use. Although they have the potential to improve the treatment of advanced malignancies, they are also associated with a substantial risk of immune-related adverse events...
March 7, 2018: Nature Reviews. Gastroenterology & Hepatology
Najmeh Khosravianfar, Jamshid Hadjati, Afshin Namdar, Roobina Boghozian, Morteza Hafezi, Mahboubeh Ashourpour, Nasim Kheshtchin, Mahsa Banitalebi, Reza Mirzaei, Seyed Alireza Razavi
Myeloid-derived suppressor cells (MDSCs) are capable of suppressing the immune response. 5-Fluorouracil (5-FU) compared to other chemotherapy drugs have shown considerable decreases in the number of MDSCs without visible effects on T, B and natural killer cells, as well as dendritic cells (DCs). DC-based vaccines considered to be appropriate candidates for cancer immunotherapy. However, due to the presence of various factors like MDSCs in tumor microenvironment, DC vaccine cannot effectively perform its function...
February 2018: Iranian Journal of Allergy, Asthma, and Immunology
Mladen Korbelik
The insult delivered by photodynamic therapy (PDT) in treated cells is oxidative stress. The main burden threatening survival of PDT-treated cells is proteotoxic damage that jeopardizes proteostasis in these cells. For dealing with this type of proteostasis impairment, cells have developed protection mechanisms operating by signaling networks. This review will outline various components of signaling networks that can be engaged in stressed cells with highlighting the emerging aspects relevant to response to PDT...
March 7, 2018: Lasers in Surgery and Medicine
Duojiao Wu, Xiangdong Wang, Hongzhi Sun
Mitochondrial malfunction is related to aging and to the onset of many diseases, such as obesity/diabetes, cancer, and cardiovascular and neurodegenerative diseases. The molecular principles of biological and toxicological processes the mitochondria can regulate should be disease-specific, cell type-specific, and drug targetable. Mitochondrial biology and toxicology is evolving and undergoing a revolution through fast-developing biotechnologies garnering increasing attention due to the importance of targeted therapies...
March 6, 2018: Cell Biology and Toxicology
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
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