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Cancer immunology

Thomas Menter, Alexandar Tzankov
Purpose: Targeting cancer cells by modulating the immune system has become an important new therapeutic option in many different malignancies. Inhibition of CTLA4/B7 and PD1/PDL1 signaling is now also being investigated and already successfully applied to various hematologic malignancies. Methods: A literature review of PubMed and results of our own studies were compiled in order to give a comprehensive overview on this topic. Results: We elucidate the pathophysiological role of immunosuppressive networks in lymphomas, ranging from changes in the cellular microenvironment composition to distinct signaling pathways such as PD1/PDL1 or CTLA4/B7/CD28...
2018: Frontiers in Oncology
Nischala Ammannagari, Ajlan Atasoy
Gastroesophageal (GE) cancers continue to be a significant cause of mortality globally. Despite therapeutic advances in oncology, the prognosis of advanced GE cancer remains exceedingly poor. Immunotherapy has caused a major paradigm shift in the field of oncology. Not all patients benefit from these agents and several studies are trying to identify predictive and prognostic biomarkers to better inform and guide treatment decisions. The potential role of immunotherapy in GE cancers is emerging. These cancer types are molecularly and immunologically heterogeneous, and this heterogeneity influences the tumor microenvironment posing a significant challenge to studying biomarkers of response to immunotherapy...
February 2018: Journal of Gastrointestinal Oncology
Nicola Silvestris, Oronzo Brunetti, Rosamaria Pinto, Daniela Petriella, Antonella Argentiero, Livia Fucci, Stefania Tommasi, Katia Danza, Simona De Summa
OBJECTIVES: Adenosquamous cancer of pancreas (ASCP) is a rare variant of pancreatic adenocarcinoma (PDAC). It is characterized by poor prognosis and lacks of literature data supporting the choice of systemic therapies. The role of immunotherapy for this malignancy is still unknown. In this study, we evaluated any differences between immune-related genes of PDAC and its adenosquamous variant with the aim to characterize these histothistotypes and eventually identify potential biomarkers useful for an immune-therapy approach in ASCP...
March 21, 2018: Expert Opinion on Therapeutic Targets
Yu-Kui Shang, Can Li, Ze-Kun Liu, Ling-Min Kong, Ding Wei, Jing Xu, Zi-Ling Wang, Huijie Bian, Zhi-Nan Chen
CD147, encoded by BSG , is a highly glycosylated transmembrane protein that belongs to the immunological superfamily and expressed on the surface of many types of cancer cells. While CD147 is best known as a potent inducer of extracellular matrix metalloproteinases, it can also function as a key mediator of inflammatory and immune responses. To systematically elucidate the function of CD147 in cancer cells, we performed an analysis of genome-wide profiling across the Cancer Cell Line Encyclopedia (CCLE). We showed that CD147 mRNA expression was much higher than that of most other genes in cancer cell lines...
February 27, 2018: Oncotarget
Martine J Kallemeijn, François G Kavelaars, Michèle Y van der Klift, Ingrid L M Wolvers-Tettero, Peter J M Valk, Jacques J M van Dongen, Anton W Langerak
Immunological aging remodels the immune system at several levels. This has been documented in particular for the T-cell receptor (TCR)αβ+ T-cell compartment, showing reduced naive T-cell outputs and an accumulation of terminally differentiated clonally expanding effector T-cells, leading to increased proneness to autoimmunity and cancer development at older age. Even though TCRαβ+ and TCRγδ+ T-cells follow similar paths of development involving V(D)J-recombination of TCR genes in the thymus, TCRγδ+ T-cells tend to be more subjected to peripheral rather than central selection...
2018: Frontiers in Immunology
Honglin Jin, Chao Wan, Zhenwei Zou, Guifang Zhao, Lingling Zhang, Yuanyuan Geng, Tong Chen, Ai Huang, Fagang Jiang, Jue-Ping Feng, Jonathan F Lovell, Jing Chen, Gang Wu, Kunyu Yang
Immunosuppressive tumor microenvironments (TMEs) create tremendous obstacles for an effective cancer therapy. Herein, we developed a melittin-RADA32 hybrid peptide hydrogel loaded with doxorubicin (DOX) for a potent chemoimmunotherapy against melanoma through the active regulation of TMEs. The formed melittin-RADA32-DOX (MRD) hydrogel has an interweaving nanofiber structure and exhibits excellent biocompatibility, controlled drug release properties both in vitro and in vivo, and an enhanced killing effect to melanoma cells...
March 20, 2018: ACS Nano
Siambi Kikete, Li Luo, Beitian Jia, Li Wang, Gregory Ondieki, Yuhong Bian
Today, cancers pose a major public health burden. Although a myriad of cancer treatments are available, only a few have achieved clinical efficacy. This is partly attributed to cancers capability to evade host immunity by converting dendritic cells (DCs) from potent stimulators to negative modulators of immunity. Dendritic cell-based immunotherapy attempts to resolve this problem by manipulating the functional characteristics of DCs. Plant-derived polysaccharides (PDPs) can stimulate the maturation of DCs conferring on them the capacity to present internalised tumorigenic antigens to naïve T cells and subsequently priming T cells to eliminate tumours...
March 19, 2018: Cytotechnology
Tuan Hiep Tran, Thi Thu Phuong Tran, Hanh Thuy Nguyen, Cao Dai Phung, Jee-Heon Jeong, Martina H Stenzel, Sung Giu Jin, Chul Soon Yong, Duy Hieu Truong, Jong Oh Kim
Crosstalk among immune cells has attracted considerable attention with the advent of immunotherapy as a novel therapeutic approach for challenging diseases, especially cancer, which is the leading cause of mortality worldwide. Dendritic cells-the key antigen-presenting cells-play a pivotal role in immunological response by presenting exogenous epitopes to T cells, which induces the self-defense mechanisms of the body. Furthermore, nanotechnology has provided promising ways for diagnosing and treating cancer in the last decade...
March 16, 2018: International Journal of Pharmaceutics
Zhijuan Qiu, Brian S Sheridan
The intestinal immune system plays an essential role in maintaining the barrier function of the gastrointestinal tract by generating tolerant responses to dietary antigens and commensal bacteria while mounting effective immune responses to enteropathogenic microbes. In addition, it has become clear that local intestinal immunity has a profound impact on distant and systemic immunity. Therefore, it is important to study how an intestinal immune response is induced and what the immunologic outcome of the response is...
February 28, 2018: Journal of Visualized Experiments: JoVE
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
Weihuang Liu, Jie Zhao, Qiaoqi Li, Qiaona Wang, Ying Zhou, Zan Tong
Dendritic cells (DCs) are important in tumor immunology. Identifying DC subset markers in the peripheral blood, which are informative for gastric cancer stages, is not only useful for prognosis but may also provide mechanistic insights into processes facilitating therapy. The present study investigated plasmacytoid dendritic cells (pDCs) and myeloid CD1c+ dendritic cells (mDC1s) in the peripheral blood of patients with gastric cancer and healthy controls using flow cytometry. Using peripheral DC staining and subset analysis, patients with gastric cancer were identified to have substantially higher numbers of peripheral pDCs and mDC1s...
April 2018: Oncology Letters
Nuria Farré, Ramon Farré, David Gozal
Obstructive Sleep Apnea (OSA) has emerged as a highly prevalent public health problem that imposes important mid-term and long-term consequences, namely cardiovascular, metabolic, cognitive and cancer-related alterations. OSA is characterized by increased upper airway resistance, alveolar hypoventilation, and recurrent upper airway obstruction during sleep. Recurrent collapse of the upper airway develops with sleep onset, and is associated with both intermittent hypoxemia and sleep fragmentation. The microbiome is a vast and complex polymicrobial ecosystem that coexists with the human organism, and has been identified as playing significant roles in the development of host immunological phenotypes...
March 13, 2018: Chest
Benedikt Hacker, Christoph Schultheiß, Michael Döring, Ursula Kurzik-Dumke
This study provides first insights into the involvement of hNOT/ALG3, the human counterpart of the Drosophila NOT and yeast ALG3 gene, in various putative molecular networks. HNOT/ALG3 encodes two translated transcripts encoding precursor proteins differing in their N-terminus and showing 33% identity with the yeast asparagine-linked glycosylation 3 (ALG3) protein. Experimental evidence for the functional homology of the proteins of fly and man in the N-glycosylation has still to be provided. In this study, using the yeast two-hybrid technique we identify 17 molecular partners of hNOT-1/ALG3-1...
March 14, 2018: Human Molecular Genetics
Marco A Moro-García, Juan C Mayo, Rosa M Sainz, Rebeca Alonso-Arias
T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form...
2018: Frontiers in Immunology
Julian A Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E Soyano, Keith L Knutson, Saranya Chumsri, Yanyan Lou
Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways...
March 15, 2018: Journal of Hematology & Oncology
Peixuan Xia, Shihua Chu, Geng Liu, Guoqing Chen, Tao Yi, Shi Feng, Hongying Zhou
Kinesin Family Member 3A (KIF3A) was recognized as a key factor of ciliogenesis and transport system of primary cilia in normal cells. However, its possible function on cancer cells has yet to be identified. In the present study, microarray tissue chips, including 230 breast cancer samples, were applied to determine the KIF3A expression pattern by immunological histological chemistry. Statistical analysis on the KIF3A expression level and the currently used clinicopathological characteristics of breast cancer patients was carried out...
April 2018: Biomedical Reports
Junichiro Kawamura, Fumiaki Sugiura, Yasushi Sukegawa, Yasumasa Yoshioka, Jin-Ichi Hida, Shoichi Hazama, Kiyotaka Okuno
The safety and immunological responsiveness of a peptide vaccine of ring finger protein 43 and 34-kDa translocase of the outer mitochondrial membrane combined with uracil-tegafur/leucovorin (UFT/LV) was previously demonstrated in metastatic colorectal cancer (CRC) in a phase I clinical trial. To clarify the survival benefit of a peptide vaccine combined with UFT/LV as adjuvant treatment, a phase II clinical trial was conducted involving patients with stage III CRC. All enrolled patients, whose human leukocyte antigen (HLA)-A status was double-blinded, were administered the same regime of a peptide vaccine and UFT/LV chemotherapy...
April 2018: Oncology Letters
Jutaek Nam, Sejin Son, Lukasz J Ochyl, Rui Kuai, Anna Schwendeman, James J Moon
Photothermal therapy (PTT) is a promising cancer treatment modality, but PTT generally requires direct access to the source of light irradiation, thus precluding its utility against disseminated, metastatic tumors. Here, we demonstrate that PTT combined with chemotherapy can trigger potent anti-tumor immunity against disseminated tumors. Specifically, we have developed polydopamine-coated spiky gold nanoparticles as a new photothermal agent with extensive photothermal stability and efficiency. Strikingly, a single round of PTT combined with a sub-therapeutic dose of doxorubicin can elicit robust anti-tumor immune responses and eliminate local as well as untreated, distant tumors in >85% of animals bearing CT26 colon carcinoma...
March 14, 2018: Nature Communications
Yangming Gong, Peng Peng, Pingping Bao, Weijian Zhong, Yan Shi, Kai Gu, Ying Zheng, Chunxiao Wu, Sanjun Cai, Ye Xu, Jun Sheng, Fan Wu
BACKGROUND: The incidence and mortality rate of colorectal cancer (CRC) have increased dramatically over the past 3 decades in China due to changes in lifestyle factors. Early detection and treatment guidelines for asymptomatic cases have shown to improve CRC control in developed countries. In response to these challenges, the Shanghai Municipal Government launched a community-based CRC screening program in 2012. MATERIALS AND METHODS: Free initial screening, inclusive of immunochemical fecal occult blood and risk assessment (questionnaire), was provided by community health centers in Shanghai...
March 14, 2018: Oncologist
David A Schaer, Richard P Beckmann, Jack A Dempsey, Lysiane Huber, Amelie Forest, Nelusha Amaladas, Yanxia Li, Ying Cindy Wang, Erik R Rasmussen, Darin Chin, Andrew Capen, Carmine Carpenito, Kirk A Staschke, Linda A Chung, Lacey M Litchfield, Farhana F Merzoug, Xueqian Gong, Philip W Iversen, Sean Buchanan, Alfonso de Dios, Ruslan D Novosiadly, Michael Kalos
Abemaciclib, an inhibitor of cyclin dependent kinases 4 and 6 (CDK4/6), has recently been approved for the treatment of hormone receptor-positive breast cancer. In this study, we use murine syngeneic tumor models and in vitro assays to investigate the impact of abemaciclib on T cells, the tumor immune microenvironment and the ability to combine with anti-PD-L1 blockade. Abemaciclib monotherapy resulted in tumor growth delay that was associated with an increased T cell inflammatory signature in tumors. Combination with anti-PD-L1 therapy led to complete tumor regressions and immunological memory, accompanied by enhanced antigen presentation, a T cell inflamed phenotype, and enhanced cell cycle control...
March 13, 2018: Cell Reports
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