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https://www.readbyqxmd.com/read/28210259/resolution-of-cancer-promoting-inflammation-a-new-approach-for-anticancer-therapy
#1
REVIEW
Qi Zhang, Bo Zhu, Yongsheng Li
Inflammation is a protective response that eliminates harmful stimuli and restores tissue homeostasis, whereas the failure to resolve inflammation leads to the development of malignancies. Immune cells in the tumor inflammatory microenvironment endow cancer cells with their specific hallmarks, including mutations, metabolic reprograming, angiogenesis, invasion, and metastasis. Targeting the inflammatory microenvironment with anti-inflammatory drugs (e.g., aspirin) or by enhancing antitumor immunity (e.g., chimeric antigen receptor T cell therapy) has been extensively investigated and has achieved promising results in many cancers...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28210081/role-of-lap-cd4-t-cells-in-the-tumor-microenvironment-of-colorectal-cancer
#2
Wu Zhong, Zhi-Yuan Jiang, Lei Zhang, Jia-Hao Huang, Shi-Jun Wang, Cun Liao, Bin Cai, Li-Sheng Chen, Sen Zhang, Yun Guo, Yun-Fei Cao, Feng Gao
AIM: To investigate the abundance and potential functions of LAP(+)CD4(+) T cells in colorectal cancer (CRC). METHODS: Proportions of LAP(+)CD4(+) T cells were examined in peripheral blood and tumor/paratumor tissues of CRC patients and healthy controls using flow cytometry. Expression of phenotypic markers such as forkhead box (Fox)p3, cytotoxic T-lymphocyte-associated protein (CTLA)-4, chemokine CC receptor (CCR)4 and CCR5 was measured using flow cytometry. LAP(-)CD4(+) and LAP(+)CD4(+) T cells were isolated using a magnetic cell-sorting system and cell purity was analyzed by flow cytometry...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28210073/macrophages-as-key-drivers-of-cancer-progression-and-metastasis
#3
REVIEW
Sebastian R Nielsen, Michael C Schmid
Macrophages are one of the most abundant immune cells in the tumour microenvironment of solid tumours and their presence correlates with reduced survival in most cancers. Macrophages are present at all stages of tumour progression and stimulate angiogenesis, tumour cell invasion, and intravasation at the primary site. At the metastatic site, macrophages and monocytes prepare for the arrival of disseminated tumour cells and promote their extravasation and survival by inhibiting immune-mediated clearance or by directly engaging with tumour cells to activate prosurvival signalling pathways...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28209270/crosstalk-between-glucocorticoids-and-il-4-modulates-ym1-expression-in-alternatively-activated-myeloid-cells
#4
Nathalie Ng Kuet Leong, Frank Brombacher, Alexander H Dalpke, Michael Weitnauer
Airway epithelial cells induce a tolerogenic microenvironment by modulating immune cells in the lung. We recently showed that the supernatant of airway epithelial cells induces two marker genes of alternative activation, Ym1 and Ms4a8a, in respiratory myeloid cells. This induction was partially mediated by glucocorticoids, secreted by airway epithelial cells. In this study, we further investigated Ym1 and Ms4a8a regulation in alternatively activated myeloid cells in the presence of the TH2 cytokines IL-4 and IL-13...
February 9, 2017: Immunobiology
https://www.readbyqxmd.com/read/28209174/mouse-genomic-screen-reveals-novel-host-regulator-of-metastasis
#5
Toni Celià-Terrassa, Yibin Kang
Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.
February 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28207637/the-efficacy-of-a-prevascularized-retrievable-poly-d-l-lactide-co-%C3%AE%C2%B5-caprolactone-subcutaneous-scaffold-as-transplantation-site-for-pancreatic-islets
#6
Alexandra M Smink, Shiri Li, Don T Hertsig, Bart J de Haan, Leendert Schwab, Aart A van Apeldoorn, Eelco de Koning, Marijke M Faas, Jonathan R T Lakey, Paul de Vos
BACKGROUND: The liver as transplantation site for human pancreatic islets is a harsh microenvironment for islets and it lacks the ability to retrieve the graft. A retrievable, extrahepatic transplantation site that mimics the pancreatic environment is desired. Ideally this transplantation site should be located subdermal for easy surgical-access but this never resulted in normoglycemia. Here we describe the design and efficacy of a novel prevascularized, subcutaneously implanted, retrievable poly (D,L-lactide-co-ε-caprolactone) (PDLLCL) scaffold...
February 15, 2017: Transplantation
https://www.readbyqxmd.com/read/28207184/an-im-penetrable-shield-how-the-tumor-microenvironment-protects-cancer-stem-cells
#7
Theresa Relation, Massimo Dominici, Edwin M Horwitz
Cancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules...
February 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#8
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28202513/myeloid-cells-that-impair-immunotherapy-are-restored-in-melanomas-which-acquire-resistance-to-braf-inhibitors
#9
Shannon M Steinberg, Tamer Shabaneh, Peisheng Zhang, Viktor Martyanov, Zhenghui Li, Brian Malik, Tammara Wood, Andrea Boni, Aleksey Molodtsov, Christina V Angeles, Tyler J Curiel, Michael Whitfield, Mary Jo Turk
Acquired resistance to BRAFV600E inhibitors (BRAFi) in melanoma remains a common clinical obstacle, as is the case for any targeted drug therapy that can be developed given the plastic nature of cancers. While there has been significant focus on the cancer cell-intrinsic properties of BRAFi resistance, the impact of BRAFi resistance on host immunity has not been explored. Here we provide preclinical evidence that resistance to BRAFi in an autochthonous mouse model of melanoma is associated with restoration of myeloid-derived suppressor cells (MDSC) in the tumor microenvironment initially reduced by BRAFi treatment...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28202039/immune-modulation-of-some-autoimmune-diseases-the-critical-role-of-macrophages-and-neutrophils-in-the-innate-and-adaptive-immunity
#10
REVIEW
Kely Campos Navegantes, Rafaelli de Souza Gomes, Priscilla Aparecida Tártari Pereira, Paula Giselle Czaikoski, Carolina Heitmann Mares Azevedo, Marta Chagas Monteiro
Macrophages and neutrophils are key components involved in the regulation of numerous chronic inflammatory diseases, infectious disorders, and especially certain autoimmune disease. However, little is known regarding the contribution of these cells to the pathogenesis of autoimmune disorders. Recent studies have aimed to clarify certain important factors affecting the immunogenicity of these cells, including the type and dose of antigen, the microenvironment of the cell-antigen encounter, and the number, subset, and phenotype of these cells, which can prevent or induce autoimmune responses...
February 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28201978/multiple-myeloma-and-the-immune-microenvironment
#11
Yawara Kawano, Aldo M Roccaro, Jamil Azzi, Irene M Ghobrial
One of the great advances in the field of cancer therapy in recent years is the emergence of immune therapies. Immune therapies, especially immune checkpoint inhibitors, have shown promising results in pre-clinical models and clinical trials of solid tumors, such as melanoma, breast cancer and lung cancer. Therapeutic strategies targeting the immune microenvironment have also been applied to hematological malignancies such as multiple myeloma (MM), a plasma cell neoplasia characterized by clonal expansion of malignant plasma cells mainly in the bone marrow (BM)...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28201977/targeting-the-immune-niche-within-the-bone-marrow-microenvironment-the-rise-of-immunotherapy-in-multiple-myeloma
#12
Klaus Podar, D Jäger
Multiple Myeloma (MM) cells inhibit the development of an effective anti-MM immune response via defects in T cell function, ineffective antigen presentation; reduced phagocytic capacity; natural killer and dendritic cell dysfunction; decreased responsiveness to IL-2 and defects in B cell immunity; upregulation of inhibitory pathways; and production of excessive pro-inflammatory cytokines. Moreover, immune cells including plasmacytoid dendritic cells and macrophages trigger tumor cell proliferation, survival, and drug resistance...
February 13, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28199990/activation-of-nk-cells-and-disruption-of-pd-l1-pd-1-axis-two-different-ways-for-lenalidomide-to-block-myeloma-progression
#13
REVIEW
Massimo Giuliani, Bassam Janji, Guy Berchem
Natural Killer (NK) cells play a critical role against tumor cells in hematological malignancies. Their activating receptors are essential in tumor cell killing. In Multiple Myeloma (MM) patients, NK cell differentiation, activation and cytotoxic potential are strongly impaired leading to MM escape from immune surveillance in tissues and bone marrow. Mechanisms used by MM to affect NK cell functions are mediated by the release of soluble factors, the expression of activating and inhibitory NK cell ligands, and the expression of immune check-point inhibitors...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28199204/the-crossroads-between-cancer-immunity-and-autoimmunity-antibodies-to-self-antigens
#14
Monica Benvenuto, Rosanna Mattera, Laura Masuelli, Ilaria Tresoldi, Maria Gabriella Giganti, Giovanni Vanni Frajese, Vittorio Manzari, Andrea Modesti, Roberto Bei
The production of autoantibodies to self antigens is dependent on the failure of immune tolerance. Cancer cells express antigens which elicit a spontaneous immune response in cancer patients. The repertoire of autoantibodies found in cancer patients partly covers that of patients with autoimmune diseases. Biological activities of autoantibodies to self antigens may induce paraneoplastic syndromes which reflect the attempt of cancer patients to counteract tumor growth. Autoantibodies with similar specificities may have different effects in cancer and autoimmune disease patients due to different immunological microenvironments...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28197389/adaptive-resistance-to-anti-pd1-therapy-by-tim-3-upregulation-is-mediated-by-the-pi3k-akt-pathway-in-head-and-neck-cancer
#15
Gulidanna Shayan, Raghvendra Srivastava, Jing Li, Nicole Schmitt, Lawrence P Kane, Robert L Ferris
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197388/inhibition-of-tumor-growth-and-metastasis-by-emmprin-multiple-antigenic-peptide-map-vaccination-is-mediated-by-immune-modulation
#16
Elina Simanovich, Vera Brod, Maya M Rahat, Ella Drazdov, Miriam Walter, Jivan Shakya, Michal A Rahat
Previously, we have identified a new epitope in EMMPRIN, a multifunctional protein that mediates tumor cell-macrophage interactions and induces both MMP-9 and VEGF. Here, we synthesized this epitope as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, and sometimes regressed, tumor growth in a dose-dependent manner, reaching 94%, 71% and 72% inhibition, respectively, at a 50 μg dose (p < 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197385/prognostic-and-predictive-aspects-of-the-tumor-immune-microenvironment-and-immune-checkpoints-in-malignant-pleural-mesothelioma
#17
Elly Marcq, Vasiliki Siozopoulou, Jorrit De Waele, Jonas van Audenaerde, Karen Zwaenepoel, Eva Santermans, Niel Hens, Patrick Pauwels, Jan P van Meerbeeck, Evelien L J Smits
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tissue sections from 54 MPM patients (40 at time of diagnosis; 14 treated with chemotherapy)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197383/analysis-of-the-prognostic-role-of-an-immune-checkpoint-score-in-resected-non-small-cell-lung-cancer-patients
#18
Marta Usó, Eloísa Jantus-Lewintre, Silvia Calabuig-Fariñas, Ana Blasco, Eva García Del Olmo, Ricardo Guijarro, Miguel Martorell, Carlos Camps, Rafael Sirera
Tumors develop mechanisms to recruit tolerogenic immune cells and to induce the expression of molecules that act as immune checkpoints. This regulation of the immune microenvironment favors immune tolerance to the neoplastic cells. In this study, we have investigated the prognostic role of immune-checkpoint expression markers in a cohort of resectable non-small cell lung cancer (NSCLC) patients. RNA was isolated from fresh-frozen lung specimens (tumor and normal lung) (n = 178). RTqPCR was performed to analyze the relative expression of 20 immune-related genes that were normalized by the use of endogenous genes selected by GeNorm algorithm...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197366/compensatory-upregulation-of-pd-1-lag-3-and-ctla-4-limits-the-efficacy-of-single-agent-checkpoint-blockade-in-metastatic-ovarian-cancer
#19
Ruea-Yea Huang, Ariel Francois, Aj Robert McGray, Anthony Miliotto, Kunle Odunsi
Tumor-associated or -infiltrating lymphocytes (TALs or TILs) co-express multiple immune inhibitory receptors that contribute to immune suppression in the ovarian tumor microenvironment (TME). Dual blockade of PD-1 along with LAG-3 or CTLA-4 has been shown to synergistically enhance T-cell effector function, resulting in a delay in murine ovarian tumor growth. However, the mechanisms underlying this synergy and the relative contribution of other inhibitory receptors to immune suppression in the ovarian TME are unknown...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197361/nkp30-isoforms-and-nkp30-ligands-are-predictive-biomarkers-of-response-to-imatinib-mesylate-in-metastatic-gist-patients
#20
Sylvie Rusakiewicz, Aurélie Perier, Michaela Semeraro, Jonathan M Pitt, Elke Pogge von Strandmann, Katrin S Reiners, Sandrine Aspeslagh, Christelle Pipéroglou, Frédéric Vély, Alexandre Ivagnes, Sarah Jegou, Niels Halama, Loic Chaigneau, Pierre Validire, Christos Christidis, Thierry Perniceni, Bruno Landi, Anne Berger, Nicolas Isambert, Julien Domont, Sylvie Bonvalot, Philippe Terrier, Julien Adam, Jean-Michel Coindre, Jean-François Emile, Vichnou Poirier-Colame, Kariman Chaba, Benedita Rocha, Anne Caignard, Antoine Toubert, David Enot, Joachim Koch, Aurélien Marabelle, Marion Lambert, Sophie Caillat-Zucman, Serge Leyvraz, Christian Auclair, Eric Vivier, Alexander Eggermont, Christophe Borg, Jean-Yves Blay, Axel Le Cesne, Olivier Mir, Laurence Zitvogel
Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST...
2017: Oncoimmunology
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