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https://www.readbyqxmd.com/read/29352857/combining-chemotherapy-with-pd-1-blockade-in-nsclc
#1
REVIEW
Matthen Mathew, Thomas Enzler, Catherine A Shu, Naiyer A Rizvi
Antitumor immunity relies on the ability of the immune system to recognize tumor cells as foreign and eliminate them. An effective immune response in this setting is due to surveillance of tumor-specific antigens that induce an adaptive immune response resulting in T-cell mediated cytotoxicity. Immune checkpoint inhibitors, specifically those targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, have demonstrated promising activity in non-small cell lung cancer (NSCLC). However, there remains a crucial need for better treatment strategies for the majority of patients with advanced NSCLC, particularly in the frontline setting...
January 17, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29352201/cross-species-transcriptional-analysis-reveals-conserved-and-host-specific-neoplastic-processes-in-mammalian-glioma
#2
Nina P Connolly, Amol C Shetty, Jesse A Stokum, Ina Hoeschele, Marni B Siegel, C Ryan Miller, Anthony J Kim, Cheng-Ying Ho, Eduardo Davila, J Marc Simard, Scott E Devine, John H Rossmeisl, Eric C Holland, Jeffrey A Winkles, Graeme F Woodworth
Glioma is a unique neoplastic disease that develops exclusively in the central nervous system (CNS) and rarely metastasizes to other tissues. This feature strongly implicates the tumor-host CNS microenvironment in gliomagenesis and tumor progression. We investigated the differences and similarities in glioma biology as conveyed by transcriptomic patterns across four mammalian hosts: rats, mice, dogs, and humans. Given the inherent intra-tumoral molecular heterogeneity of human glioma, we focused this study on tumors with upregulation of the platelet-derived growth factor signaling axis, a common and early alteration in human gliomagenesis...
January 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29350534/discovery-of-tetrahydroisoquinoline-containing-cxcr4-antagonists-with-improved-in-vitro-admet-properties
#3
Eric J Miller, Edgars Jecs, Valarie M Truax, Brooke M Katzman, Yesim A Tahirovic, Robert J Wilson, Katie M Kuo, Michelle B Kim, Huy H Nguyen, Manohar T Saindane, Huanyu Zhao, Tao Wang, Chi S Sum, Mary Ellen Cvijic, Gretchen M Schroeder, Lawrence J Wilson, Dennis C Liotta
CXCR4 is a 7-transmembrane receptor expressed by hematopoietic stem cells and progeny, as well as by ≥ 48 different cancers types. CXCL12, the only chemokine ligand of CXCR4, is secreted within the tumor microenvironment, providing sanctuary for CXCR4+ tumor cells from immune surveillance and chemotherapeutic elimination by 1) stimulating pro-survival signaling and 2) recruiting CXCR4+ immunosuppressive leukocytes. Additionally, distant CXCL12-rich niches attract and support CXCR4+ metastatic growths. Accordingly, CXCR4 antagonists can potentially obstruct CXCR4-mediated pro-survival signaling, recondition the CXCR4+ leukocyte infiltrate from immunosuppressive to immunoreactive, and inhibit CXCR4+ cancer cell metastasis...
January 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29349763/immune-checkpoint-blockade-for-breast-cancer
#4
April Swoboda, Rita Nanda
An effective antitumor immune response requires interaction between cells of the adaptive and innate immune system. Three key elements are required: generation of activated tumor-directed T cells, infiltration of activated T cells into the tumor microenvironment, and killing of tumor cells by activated T cells. Tumor immune evasion can occur as a result of the disruption of each of these three key T cell activities, resulting in three distinct cancer-immune phenotypes. The immune inflamed phenotype, characterized by the presence of a robust tumor immune infiltrate, suggests impaired activated T cell killing of tumor cells related to the presence of inhibitory factors...
2018: Cancer Treatment and Research
https://www.readbyqxmd.com/read/29348848/pd-l1-expression-in-tumor-tissue-and-peripheral-blood-of-patients-with-oral-squamous-cell-carcinoma
#5
Manuel Weber, Falk Wehrhan, Christoph Baran, Abbas Agaimy, Maike Büttner-Herold, Raimund Preidl, Friedrich W Neukam, Jutta Ries
Background: Immune checkpoints like programmed cell death-1 (PD-1) and its ligand PD-L1 are involved in immune escape mechanisms of solid tumors including oral squamous cell carcinoma (OSCC). Inhibitors of the pathway are successfully used for treating especially advanced disease. However, the physiological relevance of PD-1/PD-L1-signaling in OSCC is insufficiently understood. The aim of the study was to analyze if PD-L1 expression in tumor tissue and peripheral blood samples of OSCC patients is associated with histomorphological tumor parameters and if PD-L1 expression in patients is different from controls...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348685/overexpression-of-adhesion-molecules-and-barrier-molecules-is-associated-with-differential-infiltration-of-immune-cells-in-non-small-cell-lung-cancer
#6
Young Kwang Chae, Wooyoung M Choi, William H Bae, Jonathan Anker, Andrew A Davis, Sarita Agte, Wade T Iams, Marcelo Cruz, Maria Matsangou, Francis J Giles
Immunotherapy is emerging as a promising option for lung cancer treatment. Various endothelial adhesion molecules, such as integrin and selectin, as well as various cellular barrier molecules such as desmosome and tight junctions, regulate T-cell infiltration in the tumor microenvironment. However, little is known regarding how these molecules affect immune cells in patients with lung cancer. We demonstrated for the first time that overexpression of endothelial adhesion molecules and cellular barrier molecule genes was linked to differential infiltration of particular immune cells in non-small cell lung cancer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348577/targeting-b-cell-receptor-signalling-in-cancer-preclinical-and-clinical-advances
#7
REVIEW
Jan A Burger, Adrian Wiestner
B cell receptor (BCR) signalling is crucial for normal B cell development and adaptive immunity. BCR signalling also supports the survival and growth of malignant B cells in patients with B cell leukaemias or lymphomas. The mechanism of BCR pathway activation in these diseases includes continuous BCR stimulation by microbial antigens or autoantigens present in the tissue microenvironment, activating mutations within the BCR complex or downstream signalling components and ligand-independent tonic BCR signalling...
January 19, 2018: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29346540/blood-and-lymphatic-vessels-contribute-to-the-impact-of-the-immune-microenvironment-on-clinical-outcome-in-non-small-cell-lung-cancer
#8
Giovanna Armani, Denise Madeddu, Giulia Mazzaschi, Giovanni Bocchialini, Francesco Sogni, Caterina Frati, Bruno Lorusso, Angela Falco, Costanza Annamaria Lagrasta, Stefano Cavalli, Chiara Mangiaracina, Rocchina Vilella, Gabriella Becchi, Letizia Gnetti, Emilia Corradini, Eugenio Quaini, Konrad Urbanek, Matteo Goldoni, Paolo Carbognani, Luca Ampollini, Federico Quaini
OBJECTIVES: Lymphangiogenesis plays a critical role in the immune response, tumour progression and therapy effectiveness. The aim of this study was to determine whether the interplay between the lymphatic and the blood microvasculature, tumour-infiltrating lymphocytes and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) immune checkpoint constitutes an immune microenvironment affecting the clinical outcome of patients with non-small-cell lung cancer. METHODS: Samples from 50 squamous cell carcinomas and 42 adenocarcinomas were subjected to immunofluorescence to detect blood and lymphatic vessels...
January 15, 2018: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/29346528/a-novel-stromal-lncrna-signature-reprograms-fibroblasts-to-promote-the-growth-of-oral-squamous-cell-carcinoma-via-lncrna-caf-interleukin-33
#9
Liang Ding, Jing Ren, Dongya Zhang, Yi Li, Xiaofeng Huang, Qingang Hu, Hui Wang, Yuxian Song, Yanhong Ni, Yayi Hou
Stromal carcinoma-related fibroblasts (CAFs) are the main type of non-immune cells in the tumor microenvironment (TME). CAFs interact with cancer cells to promote tumor proliferation. Long non-coding RNAs (lncRNAs) are known to regulate cell growth, apoptosis, and metastasis of cancer cells, but their role in stromal cells is unclear. Using RNA sequencing, we identified a stromal lncRNA signature during the transformation of CAFs from normal fibroblasts (NFs) in oral squamous cell carcinoma (OSCC). We uncovered an uncharacterized lncRNA, FLJ22447, which was remarkably up-regulated in CAFs, referred to LncRNA-CAF (Lnc-CAF) hereafter...
January 13, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29345636/promoting-the-accumulation-of-tumor-specific-t-cells-in-tumor-tissues-by-dendritic-cell-vaccines-and-chemokine-modulating-agents
#10
Nataša Obermajer, Julie Urban, Eva Wieckowski, Ravikumar Muthuswamy, Roshni Ravindranathan, David L Bartlett, Pawel Kalinski
This protocol describes how to induce large numbers of tumor-specific cytotoxic T cells (CTLs) in the spleens and lymph nodes of mice receiving dendritic cell (DC) vaccines and how to modulate tumor microenvironments (TMEs) to ensure effective homing of the vaccination-induced CTLs to tumor tissues. We also describe how to evaluate the numbers of tumor-specific CTLs within tumors. The protocol contains detailed information describing how to generate a specialized DC vaccine with augmented ability to induce tumor-specific CTLs...
February 2018: Nature Protocols
https://www.readbyqxmd.com/read/29345372/truncation-of-neurokinin-1-receptor-negative-regulation-of-substance-p-signaling
#11
REVIEW
Sergei Spitsin, Vasiliki Pappa, Steven D Douglas
Substance P (SP) is a tachykinin peptide, which triggers intracellular signaling in the nervous and immune systems, as well as, other local and systemic events. The interaction between SP and its receptor, neurokinin-1 receptor (NK1R), results in major downstream cellular actions, which include changes in calcium fluxes, ERK, and p21-activated kinase phosphorylation and NFκB activation. Two naturally occurring variants of the NK1R, the full-length, 407 aa receptor (NK1R-F) and the truncated, 311 aa isoform (NK1R-T), mediate the actions of SP...
January 10, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345362/innate-lymphoid-cells-in-antitumor-immunity
#12
REVIEW
Bérengère Salomé, Camilla Jandus
Innate lymphoid cells (ILCs) are the most recently characterized subset of innate lymphocytes. Based on their specific transcriptional regulation, cytokine secretion pattern and effector functions ILCs mirror the different CD4 T helper cell subsets, with the unique attributes of acting locally in early phases of immune responses, in an antigen-independent manner. In this review, we discuss how ILCs have been implicated in tumorigenesis. Their presence might favor or inhibit tumor growth, depending on the cytokines released and the specific tumor microenvironment...
December 28, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345251/cancer-associated-cachexia
#13
REVIEW
Vickie E Baracos, Lisa Martin, Murray Korc, Denis C Guttridge, Kenneth C H Fearon
Cancer-associated cachexia is a disorder characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake and metabolic changes, including elevated energy expenditure, excess catabolism and inflammation. Cachexia is highly associated with cancers of the pancreas, oesophagus, stomach, lung, liver and bowel; this group of malignancies is responsible for half of all cancer deaths worldwide. Cachexia involves diverse mediators derived from the cancer cells and cells within the tumour microenvironment, including inflammatory and immune cells...
January 18, 2018: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/29345000/cell-death-under-epithelial-mesenchymal-transition-control-in-prostate-cancer-therapeutic-response
#14
REVIEW
Diane Begemann, Harry Anastos, Natasha Kyprianou
Prostate cancer is a widespread problem among men, with >160 000 new cases in 2017 alone. Androgen deprivation therapy is commonly used in prostate cancer treatment to block androgens required for cancer growth, but disease relapse after androgen deprivation therapy is both common and severe. Changes in androgen receptor signaling from androgen deprivation therapy have been linked to therapeutic resistance and tumor progression. Resistant cells can become reprogrammed to undergo epithelial-mesenchymal transition, a phenotypic switch from benign, epithelial cells to a mobile cell with mesenchymal traits...
January 17, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/29344964/recent-advances-and-opportunities-in-proteomic-analyses-of-tumor-heterogeneity
#15
REVIEW
Nicholas W Bateman, Thomas P Conrads
Solid tumor malignancies comprise a highly variable admixture of tumor and non-tumor cellular populations, forming a complex cellular ecosystem and tumor microenvironment. This tumor heterogeneity is not incidental and is known to correlate with poor patient prognosis for many cancer types. Indeed, non-malignant cell populations, such as vascular endothelial and immune cells, are known to play key roles supporting and, in some cases, driving aggressive tumor biology and represent targets of emerging therapeutics, such as anti-angiogenesis and immune checkpoint inhibitors...
January 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29344893/profiling-tumor-infiltrating-immune-cells-with-cibersort
#16
Binbin Chen, Michael S Khodadoust, Chih Long Liu, Aaron M Newman, Ash A Alizadeh
Tumor infiltrating leukocytes (TILs) are an integral component of the tumor microenvironment and have been found to correlate with prognosis and response to therapy. Methods to enumerate immune subsets such as immunohistochemistry or flow cytometry suffer from limitations in phenotypic markers and can be challenging to practically implement and standardize. An alternative approach is to acquire aggregative high dimensional data from cellular mixtures and to subsequently infer the cellular components computationally...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29343443/new-job-for-nk-cells-architects-of-the-tumor-microenvironment
#17
Lydia Dyck, Lydia Lynch
NK cells control tumor growth directly through targeted cytotoxic granule release or cytokine secretion and indirectly by orchestrating anti-tumor immune responses. In this issue of Immunity, Glasner et al. (2018) now reveal a new role for NK cells in preventing metastatic spread through controlling tumor architecture.
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29343435/paracrine-wnt5a-%C3%AE-catenin-signaling-triggers-a-metabolic-program-that-drives-dendritic-cell-tolerization
#18
Fei Zhao, Christine Xiao, Kathy S Evans, Tbalamayooran Theivanthiran, Nicholas DeVito, Alisha Holtzhausen, Juan Liu, Xiaojing Liu, David Boczkowski, Smita Nair, Jason W Locasale, Brent A Hanks
Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter...
January 16, 2018: Immunity
https://www.readbyqxmd.com/read/29342862/heterogeneous-contributing-factors-in-mpm-disease-development-and-progression-biological-advances-and-clinical-implications
#19
REVIEW
Bhairavi Tolani, Luis A Acevedo, Ngoc T Hoang, Biao He
Malignant pleural mesothelioma (MPM) tumors are remarkably aggressive and most patients only survive for 5-12 months; irrespective of stage; after primary symptoms appear. Compounding matters is that MPM remains unresponsive to conventional standards of care; including radiation and chemotherapy. Currently; instead of relying on molecular signatures and histological typing; MPM treatment options are guided by clinical stage and patient characteristics because the mechanism of carcinogenesis has not been fully elucidated; although about 80% of cases can be linked to asbestos exposure...
January 13, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29340117/the-regulation-of-pre-metastatic-niche-formation-by-neutrophils
#20
REVIEW
Jadwiga Jablonska, Stephan Lang, Ronit Vogt Sionov, Zvi Granot
Metastasis is a multistep process requiring tumor cell detachment from the primary tumor and migration to target organs through the lymphatic or blood circulatory systems. Specific organs are predisposed to metastases in certain cancers and the formation of supportive metastatic microenvironment determines tumor cell homing. Such an environment is provided by a pre-metastatic niche that is formed through the recruitment of bone marrow-derived myeloid cells, however the mechanisms of its formation are not fully understood...
December 19, 2017: Oncotarget
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