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https://www.readbyqxmd.com/read/28108950/t-cell-receptor-engineered-t-cells-for-cancer-treatment-current-status-and-future-directions
#1
REVIEW
Yu Ping, Chaojun Liu, Yi Zhang
T-cell receptor (TCR)-engineered T cells are a novel option for adoptive cell therapy used for the treatment of several advanced forms of cancer. Work using TCR-engineered T cells began more than two decades ago, with numerous preclinical studies showing that such cells could mediate tumor lysis and eradication. The success of these trials provided the foundation for clinical trials, including recent clinical successes using TCR-engineered T cells to target New York esophageal squamous cell carcinoma (NY-ESO-1)...
January 20, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28108623/tumor-induced-stromal-stat1-accelerates-breast-cancer-via-deregulating-tissue-homeostasis
#2
Victoria R Zellmer, Patricia M Schnepp, Sarah L Fracci, Xuejuan Tan, Erin N Howe, Siyuan Zhang
: The tumor microenvironment (TME) is a dynamic tissue space in which the tumor exists, plays a significant role in tumor initiation, and is a key contributor in cancer progression; however, little is known about tumor-induced changes in the adjacent tissue stroma. Herein, tumor-induced changes in the TME were explored at the morphological and molecular level to further understand cancer progression. Tumor-adjacent mammary glands (TAGs) displayed altered branching morphology, expansion of myofibroblasts, and increased mammosphere formation, broadly suggesting a tumor-induced field effect...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108545/bombesin-antagonist-based-radiotherapy-of-prostate-cancer-combined-with-wst-11-vascular-targeted-photodynamic-therapy
#3
Kwanghee Kim, Hanwen Zhang, Stephen LaRosa, Sylvia Jebiwott, Pooja Desai, Simon Y Kimm, Avigdor J Scherz, Joseph A O'Donoghue, Wolfgang A Weber, Jonathan Coleman
PURPOSE: DOTA-AR, a bombesin-antagonist peptide, has potential clinical application for targeted imaging and therapy in Gastrin Releasing Peptide receptor (GRPr) positive malignancies when conjugated with a radioisotope such as 90Y. This therapeutic potential is limited by the fast washout of the conjugates from the target tumors. WST-11 (Weizmann STeba-11 drug; a negatively charged water-soluble palladium-bacteriochlorophyll derivative, Tookad® Soluble) Vascular targeted photodynamic therapy (VTP) is a local ablation approach recently approved for use in early stage prostate cancer...
January 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28108509/differential-pi3k%C3%AE-signaling-in-cd4-t-cell-subsets-enables-selective-targeting-of-t-regulatory-cells-to-enhance-cancer-immunotherapy
#4
Samir N Khleif, Shamim Ahmad, Rasha Abu Eid, Rajeev K Shrimali, Mason Webb, Vivek Verma, Atbin Doroodchi, Zuzana Berrong, Raed N Samara, Paulo C Rodriguez, Mikayel Mkrtichyan
To modulate T cell function for cancer therapy one challenge is to selectively attenuate regulatory but not conventional CD4+ T cell subsets (Treg and Tconv). In this study we show how a functional dichotomy in Class IA PI3K isoforms in these two subsets of CD4+ T cells be exploited to target Treg while leaving Tconv intact. Studies employing isoform-specific PI3K inhibitors and a PI3Kδ-deficient mouse strain revealed that PI3Kα and PI3Kβ were functionally redundant with PI3Kδ in Tconv. Conversely, PI3Kδ was functionally critical in Treg, acting there to control TCR signaling, cell proliferation and survival...
January 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28107190/radiosynthesis-and-validation-of-%C3%A2-18f-3-fluoro-2-hydroxypropionate-18f-flac-as-a-pet-tracer-of-lactate-to-monitor-mct1-dependent-lactate-uptake-in-tumors
#5
Vincent F Van Hée, Daniel Labar, Gwenaël Dehon, Debora Grasso, Vincent Grégoire, Giulio G Muccioli, Raphaël Frédérick, Pierre Sonveaux
Cancers develop metabolic strategies to cope with their microenvironment often characterized by hypoxia, limited nutrient bioavailability and exposure to anticancer treatments. Among these strategies, the metabolic symbiosis based on the exchange of lactate between hypoxic/glycolytic cancer cells that convert glucose to lactate and oxidative cancer cells that preferentially use lactate as an oxidative fuel optimizes the bioavailability of glucose to hypoxic cancer cells. This metabolic cooperation has been described in various human cancers and can provide resistance to anti-angiogenic therapies...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107186/the-combination-of-pd-l1-expression-and-decreased-tumor-infiltrating-lymphocytes-is-associated-with-a-poor-prognosis-in-triple-negative-breast-cancer
#6
Hitomi Mori, Makoto Kubo, Rin Yamaguchi, Reiki Nishimura, Tomofumi Osako, Nobuyuki Arima, Yasuhiro Okumura, Masayuki Okido, Mai Yamada, Masaya Kai, Junji Kishimoto, Yoshinao Oda, Masafumi Nakamura
This study included patients with primary triple-negative breast cancer (TNBC) who underwent resection without neoadjuvant chemotherapy between January 2004 and December 2014. Among the 248 TNBCs studied, programmed cell death ligand-1 (PD-L1) expression was detected in 103 (41.5%) tumors, and high levels of tumor-infiltrating lymphocytes (TILs) were present in 118 (47.6%) tumors. PD-L1 expression correlated with high levels of TILs, but was not a prognostic factor. Patients with TILs-high tumors had better overall survival than those with TILs-low tumors (P = 0...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28107044/quercetin-attenuates-cell-survival-inflammation-and-angiogenesis-via-modulation-of-akt-signaling-in-murine-t-cell-lymphoma
#7
Akhilendra Kumar Maurya, Manjula Vinayak
AKT signaling is important to maintaining normal physiology. Hyperactivation of AKT signaling is frequent in cancer, which maintains a high oxidative state in a tumor microenvironment that is needed for tumor adaptation. Therefore, antioxidants are proposed to exhibit anticancer properties by interfering with the tumor microenvironment. Quercetin is an ubiquitous bioactive antioxidant rich in vegetables and beverages. The present study aimed to analyze cancer preventive property of quercetin in ascite cells of Dalton's lymphoma-bearing mice...
January 20, 2017: Nutrition and Cancer
https://www.readbyqxmd.com/read/28106852/tumor-derived-tissue-factor-aberrantly-activates-complement-and-facilitates-lung-tumor-progression-via-recruitment-of-myeloid-derived-suppressor-cells
#8
Xiao Han, Haoran Zha, Fei Yang, Bo Guo, Bo Zhu
The initiator of extrinsic coagulation, tissue factor (TF), and its non-coagulant isoform alternatively spliced TF (asTF) are closely associated with tumor development. In the tumor microenvironment, the role of TF-induced coagulation in tumor progression remains to be fully elucidated. Using TF-knockdown lung tumor cells, we showed that TF is the dominant component of procoagulant activity but is dispensable in the cellular biology of tumor cells. In a xenograft model, using immunohistochemical analysis and flow cytometry analysis of the tumor microenvironment, we demonstrated that TF-induced fibrin deposition, which is correlated with complement activation and myeloid-derived suppressor cell (MDSC) recruitment, is positively associated with tumor progression...
January 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106365/coordinatively-self-assembled-luminescent-gold-nanoparticles-fluorescence-turn-on-system-for-high-efficiency-passive-tumor-imaging
#9
Xuandi Lai, Lishan Tan, Xiulong Deng, Jinbin Liu, Aiqing Li, Jianyu Liu, Jianqiang Hu
A fluorescence turn-on system for highly efficient and prolonged tumor imaging has been established by Co2+-induced coordination self-assembly strategy, in which luminescent glutathione (GSH)-modified gold nanoparticles (LGAuNPs) are assembled into LGAuNPs assemblies (LGAuNPs-Co) through coordination bond between unoccupied orbit of Co2+ and lone pair electrons of GSH on the surface of LGAuNPs. The LGAuNPs-Co is sensitive to microenvironment pH and its quenched luminescence will be turned on in tumor tissues (acidic microenvironment), which behaves as a fluorescence turn-on system for passive tumor imaging...
January 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28106295/macrophage-polarization-anti-cancer-strategies-to-target-tumor-associated-macrophage-in-breast-cancer
#10
Muhammad Tariq, Jieqiong Zhang, Guikai Liang, Ling Ding, Qiaojun He, Bo Yang
Tumor-associated macrophages (TAMs) are the most abundant inflammatory cells and orchestrate different stages of breast cancer development. TAMs participate in the tumor angiogenesis, matrix remodeling, invasion, immunosuppression, metastasis, and chemoresistance in breast cancer. Several clinical studies indicate the association between the high influx of TAMs in tumor with poor prognosis in hepatocellular, ovarian, cervical, and breast cancer. Previously developed hypotheses have proposed that TAMs participate in antitumor responses of the body, while recently many clinical and experimental studies have revealed that TAMs in tumor microenvironment predominantly resemble with M2-like polarized macrophages and produce a high amount of anti-inflammatory factors which are directly responsible for the development of tumor...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#11
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105369/potassium-channels-of-t-lymphocytes-take-center-stage-in-the-fight-against-cancer
#12
EDITORIAL
Laura Conforti
A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K(+) homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment (TME) suppress the function of effector T cells. Furthermore, they establish that overexpression of K(+) channels in T lymphocytes counterbalances this negative effect of the TME and restores the ability of TILs to function, ultimately leading to increased survival of tumor bearing mice. Thus, K(+) channels in T lymphocytes become interesting new targets for novel immunotherapies in cancer...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105368/clinical-and-immunologic-correlates-of-response-to-pd-1-blockade-in-a-patient-with-metastatic-renal-medullary-carcinoma
#13
Kathryn E Beckermann, Pradeep C Jolly, Ju Y Kim, Jennifer Bordeaux, Igor Puzanov, W Kimryn Rathmell, Douglas B Johnson
BACKGROUND: Renal medullary carcinoma (RMC) is a rare kidney tumor that occurs in adolescent and young adults, typically in association with sickle cell trait. RMC exhibits rapid disease progression, frequent metastases at diagnosis, and dismal clinical outcomes. Currently available therapies, including cisplatin-based combination chemotherapy, multi-tyrosine kinase, and mTOR inhibitor strategies demonstrate either transient responses or minimal activity. Therefore, further molecular characterization and additional treatment strategies are urgently needed in this aggressive disease...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28104913/exosome-derived-micrornas-in-cancer-metabolism-possible-implications-in-cancer-diagnostics-and-therapy
#14
REVIEW
Marco Tomasetti, Wan Lee, Lory Santarelli, Jiri Neuzil
Malignant progression is greatly affected by dynamic cross-talk between stromal and cancer cells. Exosomes are secreted nanovesicles that have key roles in cell-cell communication by transferring nucleic acids and proteins to target cells and tissues. Recently, MicroRNAs (miRs) and their delivery in exosomes have been implicated in physiological and pathological processes. Tumor-delivered miRs, interacting with stromal cells in the tumor microenvironment, modulate tumor progression, angiogenesis, metastasis and immune escape...
January 20, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28104684/broad-and-conserved-immune-regulation-by-genetically-heterogeneous-melanoma-cells
#15
Natalie J Neubert, Laure Tillé, David Barras, Charlotte Soneson, Petra Baumgaertner, Donata Rimoldi, David Gfeller, Mauro Delorenzi, Silvia A Fuertes Marraco, Daniel E Speiser
While mutations drive cancer, it is less clear to what extent genetic defects control immune mechanisms and confer resistance to cytotoxic T lymphocyte (CTL)-based immunotherapy. Here we studied the reactions of malignant and benign melanocyte lines to CTL using flow cytometry and gene expression analyses. We found rapid and broad upregulation of immune regulatory genes, essentially triggered by CTL-derived IFNγ and augmented by TNFα. These reactions were predominantly homogenous, independent of oncogenic driver mutations and similar in benign and malignant cells...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28104683/panin-neuroendocrine-cells-promote-tumorigenesis-via-neuronal-crosstalk
#16
Smrita Sinha, Ya-Yuan Fu, Adrien Grimont, Maren Ketcham, Kelly J Lafaro, Joseph A Saglimbeni, Gokce Askan, Jennifer M Bailey, Jerry P Melchor, Yi Zhong, Min Geol Joo, Olivera Grbovic-Huezo, In-Hong Yang, Olca Basturk, Lindsey Baker, Youngkyu Park, Robert C Kurtz, David A Tuveson, Steven D Leach, Pankaj Pasricha
Nerves are a notable feature of the tumor microenvironment in some epithelial tumors, but their role in the malignant progression of pancreatic ductal adenocarcinoma (PDAC) is uncertain. Here we identify dense innervation in the microenvironment of precancerous pancreatic lesions, known as pancreatic intraepithelial neoplasms (PanIN), and describe a unique subpopulation of neuroendocrine PanIN cells that express the neuropeptide substance P (SP) receptor Neurokinin 1-R (NK1-R). Using organoid culture, we demonstrated that sensory neurons promoted the proliferation of PanIN organoids via SP-NK1-R signaling and Stat3 activation...
January 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28103506/the-effect-of-anti-angiogenic-drugs-on-regulatory-t-cells-in-the-tumor-microenvironment
#17
REVIEW
Chenxi Hu, Xiaodong Jiang
A benefit of anti-angiogenic drugs is improved tumor immune tolerance. Regulatory T cells (Tregs) in the tumor microenvironment mediate tumor immune tolerance and anti-angiogenic drugs not only indirectly affect Tregs via dendritic cells (DCs) and myeloid-derived suppressor cells (MDSCs) but they can also act directly on Tregs causing immunosuppression. Specifically, these drugs may induce differentiation and chemotaxis and reduce the number and function of Tregs by targeting vascular endothelial growth factor receptor 2 (VEGFR-2) and neuropilin-1 (NRP-1) on the cell surface...
January 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28103135/reconstitution-of-a-metastatic-resistant-tumor-microenvironment-with-cancer-associated-fibroblasts-enables-metastasis
#18
Takuya Murata, Eisuke Mekada, Robert M Hoffman
The tumor microenvironment is critical for metastasis to occur. Subcutaneous xenografts of tumors in immunodeficient mice are usually encapsulated and rarely metastasize as opposed to orthotopic tumors which metastasize if the original tumor was metastatic. In the present report, we were able to reconstitute a metastatic tumor microenvironment by subcutaneously co-transplanting a human cervical cancer cell line and human cervical cancer-associated fibroblasts (CAFs), in athymic mice, which resulted in lymph node metastasis in 40% of the animals...
January 19, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28101242/screening-and-analysis-of-breast-cancer-genes-regulated-by-the-human-mammary-microenvironment-in-a-humanized-mouse-model
#19
Mingjie Zheng, Jue Wang, Lijun Ling, Dandan Xue, Shui Wang, Yi Zhao
Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28101230/effect-of-il-17-in-the-development-of-colon-cancer-in-mice
#20
Lijuan Yang, Hao Liu, Lili Zhang, Jie Hu, Haixia Chen, Lei Wang, Xiaolin Yin, Quanhai Li, Yixin Qi
Cytokine therapy is commonly used for tumor immunotherapy. Although early studies focused directly on the tumor, current investigations are more attentive of the tumor microenvironment. Various immune cells and related cytokines in the tumor microenvironment play an important role in the occurrence and development of tumor. Interleukin (IL)-17 is the characteristic cytokine produced by Th17 cells. IL-17 has been associated with various immune responses. The results of previous studies showed that IL-17 can significantly reduce the size of transplanted tumors in tumor-bearing mice, albeit it has no effect on the survival time of mice...
December 2016: Oncology Letters
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