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cancer cell,tumor,immune surveilance

Francisco S Barreto, Adriano J M Chaves Filho, Márcia C C R de Araújo, Manoel O de Moraes, Maria E A de Moraes, Michael Maes, David F de Lucena, Danielle S Macedo
Both depression and cancer are related to a dysregulation of inflammatory and immune pathways. Indeed, depression is associated with increased expression of interferon-γ, interleukin-1β, and tumor necrosis factor α (TNF-α). In contrast, reductions of the activity of major histocompatibility complex protein molecules - class I and class II and natural killer cells are also observed. Similarly, cancers present elevated levels of TNF-α, reduced major histocompatibility complex class I and II, and natural killer cells...
April 2018: Behavioural Pharmacology
Jonuelle Acosta, Walter Wang, David M Feldser
Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor...
March 15, 2018: Oncogene
Theresa L Whiteside
Regulatory T cells (Treg) characterized by expression of FOXP3 and strong immunosuppressive activity play a key role in regulating homeostasis in health and disease. Areas covered: Human Treg are highly diverse phenotypically and functionally. In the tumor microenvironment (TME), Treg are reprogrammed by the tumor, acquiring an activated phenotype and enhanced suppressor functions. No unique phenotypic markers for Treg accumulating in human tumors exist. Treg are heterogeneous and use numerous mechanisms to mediate suppression, which either silences anti-tumor immune surveillance or prevents tissue damage by activated T cells...
March 13, 2018: Expert Opinion on Therapeutic Targets
Kimio Yonesaka, Koji Haratani, Shiki Takamura, Hitomi Sakai, Ryoji Kato, Naoki Takegawa, Takayuki Takahama, Kaoru Tanaka, Hidetoshi Hayashi, Masayuki Takeda, Shigeki Kato, Osamu Maenishi, Kazuko Sakai, Yasutaka Chiba, Takafumi Okabe, Keita Kudo, Yoshikazu Hasegawa, Hiroyasu Kaneda, Michiko Yamato, Kenji Hirotani, Masaaki Miyazawa, Kazuto Nishio, Kazuhiko Nakagawa
PURPOSE: Anti-programmed-death-1 (PD-1) immunotherapy improves survival in non-small cell lung cancer (NSCLC), but some cases are refractory to treatment, thereby requiring alternative strategies. B7-H3, an immune-checkpoint molecule, is expressed in various malignancies. To our knowledge, this study is the first to evaluate B7-H3 expression in NSCLCs treated with anti-PD-1 therapy and the therapeutic potential of a combination of anti-PD-1 therapy and B7-H3 targeting. EXPERIMENTAL DESIGN: B7-H3 expression was evaluated immunohistochemically in patients with NSCLC (n = 82), and its relationship with responsiveness to anti-PD-1 therapy and CD8+ tumor infiltrating lymphocytes (TILs) was analyzed...
March 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Claudia Fumarola, Pier Giorgio Petronini, Roberta Alfieri
Cell metabolic reprogramming is one of the main hallmarks of cancer and many oncogenic pathways that drive the cancer-promoting signals also drive the altered metabolism. This review focuses on recent data on the use of oncogene-targeting agents as potential modulators of deregulated metabolism in different solid cancers. Many drugs, originally designed to inhibit a specific target, then have turned out to have different effects involving also cell metabolism, which may contribute to the mechanisms underlying the growth inhibitory activity of these drugs...
March 9, 2018: Biochemical Pharmacology
Amedea B Seabra, Nelson Durán
Nitric oxide (NO) is an endogenous molecule that plays pivotal physiological and pathophysiological roles, particularly in cancer biology. Generally, low concentrations of NO (pico- to nanomolar range) lead to tumor promotion. In contrast, high NO concentrations (micromolar range) have pro-apoptotic functions, leading to tumor suppression, and in this case, NO is involved in immune surveillance. Under oxidative stress, inducible NO synthase (iNOS) produces high NO concentrations for antineoplastic activities...
March 1, 2018: European Journal of Pharmacology
Min Yang, Yuehua Feng, Cuihua Yue, Bin Xu, Lujun Chen, Jingting Jiang, Binfeng Lu, Yibei Zhu
OBJECTIVE: Lung cancer is one of the deadliest malignancies. The immune checkpoint-blockade (ICB) tumor therapy has led to striking improvement of long-term survival for some lung cancer patients. However, the response rate of immunotherapy is still low for lung cancer. Studying the tumor microenvironment (TME) should shed light on improvement of immunotherapy of lung cancer. Interleukin-33 (IL-33), an "alarmin" cytokine, has been implicated in tumor associated immune responses and inflammatory diseases of the lung...
2018: PloS One
Kazuyoshi Takeda, Katashi Nagamatsu, Ko Okumura
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis, a resinous material collected from numerous plants by honeybees, has historically been used as a health-promoting food. Recently, due to its potential anti-tumor effects, use of propolis has been proposed as an adjuvant therapy to chemotherapy; however, the effects of propolis on immune responses remain unclear. AIM OF THE STUDY: In this study, we examined the effects of the oral ingestion of propolis on natural killer (NK) cell activity, which is important in immune surveillance against cancer and viral infections...
February 26, 2018: Journal of Ethnopharmacology
Guillaume P Andrieu, Jordan S Shafran, Jude T Deeney, Kishan R Bharadwaj, Annapoorni Rangarajan, Gerald V Denis
Obesity and its associated pathology Type 2 diabetes are two chronic metabolic and inflammatory diseases that promote breast cancer progression, metastasis, and poor outcomes. Emerging critical opinion considers unresolved inflammation and abnormal metabolism separately from obesity; settings where they do not co-occur can inform disease mechanism. In breast cancer, the tumor microenvironment is often infiltrated with T effector and T regulatory cells programmed by metabolic signaling. The pathways by which tumor cells evade immune surveillance, immune therapies, and take advantage of antitumor immunity are poorly understood, but likely depend on metabolic inflammation in the microenvironment...
March 1, 2018: Journal of Leukocyte Biology
Angela R Elia, Matteo Grioni, Veronica Basso, Flavio Curnis, Massimo Freschi, Angelo Corti, Anna Mondino, Matteo Bellone
PURPOSE: Irregular blood flow and endothelial cell anergy, which characterize many solid tumors, hinder tumor infiltration by cytotoxic T lymphocytes (CTLs). This confers resistance to cancer immunotherapy with monoclonal antibodies directed against regulatory pathways in T lymphocytes (i.e., immune checkpoint blockade, ICB). We investigated whether NGR-TNF, a TNF derivative capable of targeting the tumor vasculature, and improving intra-tumor infiltration by activated CTLs, could sensitize tumors to ICB with antibodies specific for the PD-1 and CTLA-4 receptors...
February 28, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Hiroaki Tanaka, Tatsuro Tamura, Yoshihiro Okita, Mami Yoshii, Mao Tokumoto, Yukie Go, Chie Sakimura, Soichiro Hiramatsu, Junya Nishimura, Yoshihito Yamagoe, Masakazu Yashiro, Yuichiro Miki, Takahiro Toyokawa, Kazuya Muguruma, Kosei Hirakawa, Masaichi Ohira
There are many reports on the association between infiltrating immune cells andcancer prognosis. It is generally thought that cancer cells escape from the immune surveillance system in vivo. Cells associatedwith tumor immunosuppressive mechanisms include macrophages, regulatory T cells, bone marrow-derived immunosuppressive cells(MDSC), andneutrophils. These immunosuppressive cells enhance the production of TGF-b andIL -10 andthe expression of PDL-1 by cytokines producedby stromal cells such as cancer cells andfibroblasts, thereby inducing cytotoxic T cells lymphocytes(CTL)...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
S M Mansour Haeryfar, Christopher R Shaler, Patrick T Rudak
Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. However, whether they promote malignancy or contribute to anticancer immunity is unclear. On the one hand, MAIT cells produce IL-17A in certain locations and under certain circumstances, which could in turn facilitate neoangiogenesis, intratumoral accumulation of immunosuppressive cell populations, and cancer progression...
February 22, 2018: Cancer Immunology, Immunotherapy: CII
Paulo G Bergerot, Andrew W Hahn, Cristiane Decat Bergerot, Jeremy Jones, Sumanta Kumar Pal
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) is a novel technology that can complement tumor tissue NGS and has the potential to influence diagnosis and treatment of both localized and metastatic renal cell carcinoma (mRCC). ctDNA NGS is an attractive alternative to tumor tissue NGS because it circumvents the need for repeated, invasive tissue biopsies while providing a contemporary mutational profile of a patient's tumors. While the role of ctDNA NGS in non-small cell lung cancer and colorectal cancer is well established, studies of ctDNA NGS in mRCC are only hypothesis-generating to date...
February 20, 2018: Current Treatment Options in Oncology
Lilla Hornyák, Nikoletta Dobos, Gábor Koncz, Zsolt Karányi, Dénes Páll, Zoltán Szabó, Gábor Halmos, Lóránt Székvölgyi
Tumors are composed of abnormally transformed cell types and tissues that differ from normal tissues in their genetic and epigenetic makeup, metabolism, and immunology. Molecular compounds that modulate the immune response against neoplasms offer promising new strategies to combat cancer. Inhibitors targeting the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent therapeutic opportunities to inhibit tumor growth. Herein, we assess the biochemical role of IDO1 in tumor metabolism and immune surveillance, and review current diagnostic and therapeutic approaches that are intended to increase the effectiveness of immunotherapies against highly aggressive and difficult-to-treat IDO-expressing cancers...
2018: Frontiers in Immunology
Florian Posch, Karina Silina, Sebastian Leibl, Axel Mündlein, Holger Moch, Alexander Siebenhüner, Panagiotis Samaras, Jakob Riedl, Michael Stotz, Joanna Szkandera, Herbert Stöger, Martin Pichler, Roger Stupp, Maries van den Broek, Peter Schraml, Armin Gerger, Ulf Petrausch, Thomas Winder
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers...
2018: Oncoimmunology
Jeroen F Vermeulen, Wim Van Hecke, Elisabeth J M Adriaansen, Mieke K Jansen, Rianne G Bouma, José Villacorta Hidalgo, Paul Fisch, Roel Broekhuizen, Wim G M Spliet, Marcel Kool, Niels Bovenschen
Pediatric medulloblastomas are the most frequently diagnosed embryonal tumors of the central nervous system. Current therapies cause severe neurological and cognitive side effects including secondary malignancies. Cellular immunotherapy might be key to improve survival and to avoid morbidity. Efficient killing of tumor cells using immunotherapy requires to overcome cancer-associated strategies to evade cytotoxic immune responses. Here, we examined the immune response and immune evasion strategies in pediatric medulloblastomas...
2018: Oncoimmunology
Chun-Lin Zhao, Shuang Yu, Shu-Hui Wang, Shi-Gang Li, Zhi-Ju Wang, Sheng-Na Han
The increased expression of cluster of differentiation (CD)47 has been identified in a number of different tumor types and is recognized as an adverse prognostic factor that indicates an increased risk of mortality in patients. The binding of CD47 to signal regulatory protein α (SIRPα) inhibits the macrophage phagocytosis of tumor cells by triggering an inhibitory 'do not eat me' signal. This is one of the mechanisms used by tumor cells to evade immune surveillance. In the present study, CD47 levels and macrophage infiltration were assessed in patients with esophageal squamous cell cancer (ESCC)...
February 2018: Oncology Letters
Lijie He, Jing Wang, Dandan Chang, Dandan Lv, Haina Li, Heping Zhang
The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3+, CD4+, CD8+ and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1...
February 2018: Experimental and Therapeutic Medicine
Agnieszka Witalisz-Siepracka, Dagmar Gotthardt, Michaela Prchal-Murphy, Zrinka Didara, Ingeborg Menzl, Daniela Prinz, Leo Edlinger, Eva Maria Putz, Veronika Sexl
Cyclin-dependent kinase 8 (CDK8) is a member of the transcription-regulating CDK family. CDK8 activates or represses transcription by associating with the mediator complex or by regulating transcription factors. Oncogenic activity of CDK8 has been demonstrated in several cancer types. Targeting CDK8 represents a potential therapeutic strategy. Because knockdown of CDK8 in a natural killer (NK) cell line enhances cytotoxicity and NK cells provide the first line of immune defense against transformed cells, we asked whether inhibiting CDK8 would improve NK-cell antitumor responses...
January 31, 2018: Cancer Immunology Research
Sobha R Bodduluri, Steven Mathis, Paramahamsa Maturu, Elangovan Krishnan, Shuchismita R Satpathy, Paula M Chilton, Thomas Mitchell, Sergio A Lira, Massimo Locati, Alberto Mantovani, Venkatakrishna R Jala, Bodduluri Haribabu
The presence of mast cells in some human colorectal cancers is a positive prognostic factor, but the basis for this association is incompletely understood. Here, we found that mice with a heterozygous mutation in the adenomatous polyposis coli gene (ApcMin/+) displayed reduced intestinal tumor burdens and increased survival in a chemokine decoy receptor, ACKR2-null background, which led to discovery of a critical role for mast cells in tumor defense. ACKR2-/-ApcMin/+ tumors showed increased infiltration of mast cells, their survival advantage was lost in mast cell-deficient ACKR2-/-SA-/-ApcMin/+ mice as the tumors grew rapidly, and adoptive transfer of mast cells restored control of tumor growth...
January 30, 2018: Cancer Immunology Research
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