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https://www.readbyqxmd.com/read/29137267/tumacrophage-macrophages-transformed-into-tumor-stem-like-cells-by-virulent-genetic-material-from-tumor-cells
#1
Yizhuang Zhang, Na Zhou, Xiuyan Yu, Xuehui Zhang, Shanxin Li, Zhen Lei, Ruobi Hu, Hui Li, Yiqing Mao, Xi Wang, Jinshu Zhang, Yuan Li, Hongyan Guo, David M Irwin, Gang Niu, Huanran Tan
Tumor-associated macrophages are regarded as tumor-enhancers as they have key roles in the subversion of adaptive immunity and in inflammatory circuits that promote tumor progression. Here, we show that cancer cells can subvert macrophages yielding cells that have gained pro-tumor functions. When macrophages isolated from mice or humans are co-cultured with dead cancer cell line cells, induced to undergo apoptosis to mimic chemotherapy, up-regulation of pro-tumor gene expression was identified. Phagocytosis of apoptotic cancer cells by macrophages resulted in their transformation into tumor stem (initiating)-like cells, as indicated by the expression of epithelial markers (e...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131550/innate-and-acquired-immune-surveillance-in-the-post-dissemination-phase-of-metastasis
#2
REVIEW
Hugo Gonzalez, Isabella Robles, Zena Werb
Metastasis is responsible for the majority of death in cancer patients. Of the different steps in the metastasis cascade, the post-dissemination phase is perhaps one of the least understood. Many factors, both from the disseminated tumor cells (DTCs) and the microenvironment, impact the success of the metastatic outgrowth. In this article, we discuss the interactions between colonizing cancer cells and immune cells in the period between vascular arrest in a secondary organ and metastatic outgrowth. We address the ambiguity in the findings of current research regarding the role of immune cells in regulating the metastatic microenvironment, and their hand in determining cancer cell fate...
November 13, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29123966/pd-1-blockade-at-the-time-of-tumor-escape-potentiates-the-immune-mediated-antitumor-effects-of-a-melanoma-targeting-monoclonal-antibody
#3
Laetitia They, Henri-Alexandre Michaud, Ondine Becquart, Virginie Lafont, Bernard Guillot, Florence Boissière-Michot, Marta Jarlier, Caroline Mollevi, Jean-François Eliaou, Nathalie Bonnefoy, Laurent Gros
Tumor antigen-targeting monoclonal antibodies (TA-targeting mAbs) are used as therapeutics in many malignancies and their capacity to mobilize the host immunity puts them at the forefront of anti-cancer immunotherapies. Both innate and adaptive immune cells have been associated with the therapeutic activity of such antibodies, but tumor escape from mAb-induced tumor immune surveillance remains one of the main clinical issues. In this preclinical study, we grafted immunocompetent and immunocompromised mice with the B16F10 mouse melanoma cell line and treated them with the TA99 TA-targeting mAb to analyze the immune mechanisms associated with the tumor response and resistance to TA99 monotherapy...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29105655/pre-metastatic-cancer-exosomes-induce-immune-surveillance-by-patrolling-monocytes-at-the-metastatic-niche
#4
Michael P Plebanek, Nicholas L Angeloni, Elena Vinokour, Jia Li, Anna Henkin, Dalia Martinez-Marin, Stephanie Filleur, Reshma Bhowmick, Jack Henkin, Stephen D Miller, Igal Ifergan, Yesung Lee, Iman Osman, C Shad Thaxton, Olga V Volpert
Metastatic cancers produce exosomes that condition pre-metastatic niches in remote microenvironments to favor metastasis. In contrast, here we show that exosomes from poorly metastatic melanoma cells can potently inhibit metastasis to the lung. These "non-metastatic" exosomes stimulate an innate immune response through the expansion of Ly6C(low) patrolling monocytes (PMo) in the bone marrow, which then cause cancer cell clearance at the pre-metastatic niche, via the recruitment of NK cells and TRAIL-dependent killing of melanoma cells by macrophages...
November 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/29104473/the-inhibition-of-indoleamine-2-3-dioxygenase-1-by-connexin-43
#5
Han-Chen Lin, Chih-Jen Yang, Yu-Diao Kuan, Wei-Kuang Wang, Wen-Wei Chang, Che-Hsin Lee
Upregulation of connexin 43 (Cx43) showed potential in enhancing immune surveillance that was suppressed in the tumor microenvironment. The expression of indoleamine 2, 3-dioxygenase (IDO) is one of the crucial factors contributing to tumor immune tolerance by depletion of tryptophan and IDO-mediated tryptophan metabolites. Here, we aim to investigate the role of Cx43 in IDO production in murine tumor by using Cx43 inducers. Resveratrol (trans-3, 5, 4 '-trihydroxystilbene) is a natural plant-derived polyphenol possessing positive effect against cancer...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29102276/effect-of-cd4-count-on-treatment-toxicity-and-tumor-recurrence-in-human-immunodeficiency-virus-positive-patients-with-anal-cancer
#6
Alex K Bryant, Ross Mudgway, Minh-Phuong Huynh-Le, Daniel R Simpson, Loren K Mell, Samir Gupta, Andrew B Sharabi, James D Murphy
PURPOSE: To study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients. METHODS AND MATERIALS: From a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival...
September 22, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/29092006/novel-tools-to-assist-neoepitope-targeting-in-personalized-cancer-immunotherapy
#7
S K Saini, N Rekers, S R Hadrup
Current cancer immunotherapy approaches utilize the remarkable surveillance capacity of the human immune system, which is capable of recognizing and eliminating cancer cells based on identification of tumor-associated antigens arising as a consequence of the transformation process. Among these, mutational-derived neoepitopes have proved to be powerful targets for tumor elimination and mutational load has been shown to correlate with the clinical response to treatment with checkpoint inhibitors in many different tumor types...
October 30, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29061083/immuno-oncology-the-translational-runway-for-gene-therapy
#8
Ludger Weß, Frank Schnieders
Cancer therapy once again is experiencing a paradigm shift. This shift is based on extensive clinical experience demonstrating that cancer cannot be successfully fought by addressing single targets or pathways only. Even the combination of several neo-antigens in cancer vaccines is not sufficient for a successful, lasting tumor eradication. The focus therefore has shifted on the immune systems role in cancer and the striking abilities of cancer cells to manipulate and/or deactivate the immune system. Researchers and pharma companies have started to target the processes and cells known to support immune surveillance and the elimination of tumor cells...
October 23, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/29054599/indoleamine-2-3-dioxygenase-expression-in-primary-cutaneous-melanoma-correlates-with-breslow-thickness-and-is-of-significant-prognostic-value-for-progression-free-survival
#9
Felicia Rubel, Johannes S Kern, Kristin Technau-Hafsi, Sibylle Uhrich, Kaethe Thoma, Georg Häcker, Nikolas von Bubnoff, Frank Meiss, Dagmar von Bubnoff
The enzyme indoleamine 2,3-dioxygenase (IDO) is emerging as a facilitator of cancer development through its effects on cancer-associated inflammation. Recent studies report a significant improvement of the response rates in melanoma patients to PD-1 antibodies when IDO-inhibitors were added to the regimen. Data on IDO-expression in primary human melanomas are however incomplete and conflicting. Here, we show that the level of IDO-expression in primary human melanoma cells significantly correlates with Breslow thickness (p = 0...
October 17, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29054421/selenocompounds-in-cancer-therapy-an-overview
#10
Desirée Bartolini, Luca Sancineto, Andreza Fabro de Bem, Kenneth D Tew, Claudio Santi, Rafael Radi, Pierangelo Toquato, Francesco Galli
In vitro and in vivo experimental models clearly demonstrate the efficacy of Se compounds as anticancer agents, contingent upon chemical structures and concentrations of test molecules, as well as on the experimental model under investigation that together influence cellular availability of compounds, their molecular dynamics and mechanism of action. The latter includes direct and indirect redox effects on cellular targets by the activation and altered compartmentalization of molecular oxygen, and the interaction with protein thiols and Se proteins...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29054268/saliva-exosomics-in-cancer-molecular-characterization-of-cancer-derived-exosomes-in-saliva
#11
Taichiro Nonaka, David T W Wong
Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells and detected in saliva. Pathophysiological roles for salivary exosomes are beginning to be recognized in diseases including cancer, highlighting potential biomarkers and biological functions. Since early detection of cancer is vital for successful treatment, salivary exosomes would be advantageous in achieving a better survival rate due to their ready availability and noninvasiveness. The use of salivary exosomes may therefore be promising in the accurate detection of premalignant lesions and early-stage cancers, also for better our understanding of the molecular basis of tumorigenesis...
2017: Enzymes
https://www.readbyqxmd.com/read/29052136/human-t-cell-leukemia-virus-type-1-infection-and-adult-t-cell-leukemia
#12
Chi-Ping Chan, Kin-Hang Kok, Dong-Yan Jin
Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus discovered to cause adult T-cell leukemia (ATL), a highly aggressive blood cancer. HTLV-1 research in the past 35 years has been most revealing in the mechanisms of viral oncogenesis. HTLV-1 establishes a lifelong persistent infection in CD4(+) T lymphocytes. The infection outcome is governed by host immunity. ATL develops in 2-5% of infected individuals 30-50 years after initial exposure. HTLV-1 encodes two oncoproteins Tax and HBZ, which are required for initiation of cellular transformation and maintenance of cell proliferation, respectively...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29046675/interpreting-t-cell-cross-reactivity-through-structure-implications-for-tcr-based-cancer-immunotherapy
#13
Dinler A Antunes, Maurício M Rigo, Martiela V Freitas, Marcus F A Mendes, Marialva Sinigaglia, Gregory Lizée, Lydia E Kavraki, Liisa K Selin, Markus Cornberg, Gustavo F Vieira
Immunotherapy has become one of the most promising avenues for cancer treatment, making use of the patient's own immune system to eliminate cancer cells. Clinical trials with T-cell-based immunotherapies have shown dramatic tumor regressions, being effective in multiple cancer types and for many different patients. Unfortunately, this progress was tempered by reports of serious (even fatal) side effects. Such therapies rely on the use of cytotoxic T-cell lymphocytes, an essential part of the adaptive immune system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29032503/cd4-and-cd8-t-lymphocyte-interplay-in-controlling-tumor-growth
#14
REVIEW
Dmitrij Ostroumov, Nora Fekete-Drimusz, Michael Saborowski, Florian Kühnel, Norman Woller
The outstanding clinical success of immune checkpoint blockade has revived the interest in underlying mechanisms of the immune system that are capable of eliminating tumors even in advanced stages. In this scenario, CD4 and CD8 T cell responses are part of the cancer immune cycle and both populations significantly influence the clinical outcome. In general, the immune system has evolved several mechanisms to protect the host against cancer. Each of them has to be undermined or evaded during cancer development to enable tumor outgrowth...
October 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29027231/the-renaissance-of-anti-neoplastic-immunity-from-tumor-cell-demise
#15
REVIEW
Yuting Ma, Jonathan M Pitt, Qingqing Li, Heng Yang
Cancer therapies can temporarily reduce tumor burdens by inducing malignant cell death. However, cancer cure is still far from realization because tumors often gain resistance to current treatment and eventually relapse. Accumulating evidence suggests that successful cancer interventions require anti-tumor immunity. Therapy-induced cell stress responses ultimately result in one or more cell death modalities, including apoptosis, autophagy, necroptosis, and pyroptosis. These irreversible dying processes are accompanied by active or passive release of cell death-associated molecular patterns (CDAMPs), which can be sensed by corresponding pattern recognition receptors (PRR) on tumor-infiltrating immune cells...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/29021794/cd95-fas-non-apoptotic-signaling-pathways-and-kinases
#16
REVIEW
Matthieu Le Gallo, Amanda Poissonnier, Patrick Blanco, Patrick Legembre
Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28978138/il-33-blockade-suppresses-tumor-growth-of-human-lung-cancer-through-direct-and-indirect-pathways-in-a-preclinical-model
#17
Kailing Wang, Shan Shan, Zongjun Yang, Xia Gu, Yuanyuan Wang, Chunhong Wang, Tao Ren
Non-small-cell lung cancer (NSCLC) is the most common type in lung cancer, a leading cause of cancer-related death worldwide. Our previous study unraveled a pro-cancer function of IL-33 in fueling outgrowth and metastasis of human NSCLC cells. Herein, we determined that interfere with IL-33 activity was an effective strategy for limiting NSCLC tumor growth using a preclinical model with human NSCLC xenografts. IL-33 blockade efficiently inhibited tumor growth of NSCLC xenografts in immune-deficient mice. Mechanistically, IL-33 blockade suppressed outgrowth capacity of human NSCLC cells...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977839/genetic-defects-of-the-irf1-mediated-major-histocompatibility-complex-class-i-antigen-presentation-pathway-occur-prevalently-in-the-jak2-gene-in-non-small-cell-lung-cancer
#18
Tao Shen, Zhengming Chen, Zhizhuang Joe Zhao, Jie Wu
Recognition of major histocompatibility complex (MHC) class I antigens on tumor cells by cytotoxic T cells is involved in T cell-mediated tumor immune surveillance and immune checkpoint therapy. The interferon-γ (IFNγ)-IRF1 signaling pathway regulates MHC class I antigen presentation. To examine genetic defects of the IFNγ-IRF1 pathway in non-small cell lung cancer (NSCLC), we analyzed The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LuAd) and lung squamous cell carcinoma (LuSc) data. Loss-of-function (LOF) genetic alterations of the IFNγ-IRF1 pathway genes (IFNGR1, IFNGR2, JAK1, JAK2, STAT1, IRF1) were found in 64 (6...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28955335/translational-significance-for-tumor-metastasis-of-tumor-associated-macrophages-and-epithelial-mesenchymal-transition
#19
REVIEW
Wenzhe Song, Roberta Mazzieri, Tao Yang, Glenda C Gobe
The tumor microenvironment determines development and progression of many cancers. Epithelial-mesenchymal transition (EMT) is fundamental to tumor progression and metastasis not only by increasing invasiveness but also by increasing resistance to cell death, senescence, and various cancer therapies; determining inflammation and immune surveillance; and conferring stem cell properties. It does this by enabling polarized epithelial cells to transform into cells with a mesenchymal, and therefore motile, phenotype...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28948003/the-hedgehog-gli-pathway-in-embryonic-development-and-cancer-implications-for-pulmonary-oncology-therapy
#20
REVIEW
Leonel Armas-López, Joaquín Zúñiga, Oscar Arrieta, Federico Ávila-Moreno
Transcriptional regulation and epigenetic mechanisms closely control gene expression through diverse physiological and pathophysiological processes. These include the development of germ layers and post-natal epithelial cell-tissue differentiation, as well as, involved with the induction, promotion and/or progression of human malignancies. Diverse studies have shed light on the molecular similarities and differences involved in the stages of embryological epithelial development and dedifferentiation processes in malignant tumors of epithelial origin, of which many focus on lung carcinomas...
September 1, 2017: Oncotarget
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