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Cancer microenvironment

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https://www.readbyqxmd.com/read/28651374/cd70-a-novel-target-of-car-t-cell-therapy-for-gliomas
#1
Linchun Jin, Haitao Ge, Yu Long, Changlin Yang, Yifan Emily Chang, Luyan Mu, Elias J Sayour, Gabriel De Leon, Qiong J Wang, James C Yang, Paul S Kubilis, Hongbo Bao, Songsong Xia, Dunyue Lu, Yingjun Kong, Li Hu, Yujiao Shang, Chencheng Jiang, Jing Nie, Shimin Li, Yunhe Gu, Jiahang Sun, Duane A Mitchell, Zhiguo Lin, Jianping Huang
Background: Cancer immunotherapy represents a promising treatment approach for malignant-gliomas, but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified CD70 as a novel immunosuppressive ligand and glioma target. Methods: Normal tissues derived from 52 different organs, and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression...
June 23, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28650644/combination-of-plant-virus-nanoparticle-based-in-situ-vaccination-with-chemotherapy-potentiates-antitumor-response
#2
Karin L Lee, Abner A Murray, Duc H T Le, Mee Rie Sheen, Sourabh Shukla, Ulrich Commandeur, Steven Fiering, Nicole F Steinmetz
Immunotherapeutics are gaining more traction in the armamentarium used to combat cancer. Specifically, in situ vaccination strategies have gained interest because of their ability to alter the tumor microenvironment to an antitumor state. Herein, we investigate whether flexuous plant virus-based nanoparticles formed by the potato virus X (PVX) can be used as an immunotherapeutic for in situ vaccine monotherapy. We further developed dual chemo-immunotherapeutics by incorporating doxorubicin (DOX) into PVX yielding a dual-functional nanoparticle (PVX-DOX) or by coadministration of the two therapeutic regimes, PVX immunotherapy and DOX chemotherapy (PVX+DOX)...
June 26, 2017: Nano Letters
https://www.readbyqxmd.com/read/28650339/ilc2-modulated-t-cell-to-mdsc-balance-is-associated-with-bladder-cancer-recurrence
#3
Mathieu F Chevalier, Sara Trabanelli, Julien Racle, Bérengère Salomé, Valérie Cesson, Dalila Gharbi, Perrine Bohner, Sonia Domingos-Pereira, Florence Dartiguenave, Anne-Sophie Fritschi, Daniel E Speiser, Cyrill A Rentsch, David Gfeller, Patrice Jichlinski, Denise Nardelli-Haefliger, Camilla Jandus, Laurent Derré
Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent tumor despite intravesical immunotherapy instillation with the bacillus Calmette-Guérin (BCG) vaccine. In a prospective longitudinal study, we took advantage of BCG instillations, which increase local immune infiltration, to characterize immune cell populations in the urine of patients with NMIBC as a surrogate for the bladder tumor microenvironment. We observed an infiltration of neutrophils, T cells, monocytic myeloid-derived suppressor cells (M-MDSCs), and group 2 innate lymphoid cells (ILC2)...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650338/ifn-%C3%AE-related-mrna-profile-predicts-clinical-response-to-pd-1-blockade
#4
Mark Ayers, Jared Lunceford, Michael Nebozhyn, Erin Murphy, Andrey Loboda, David R Kaufman, Andrew Albright, Jonathan D Cheng, S Peter Kang, Veena Shankaran, Sarina A Piha-Paul, Jennifer Yearley, Tanguy Y Seiwert, Antoni Ribas, Terrill K McClanahan
Programmed death-1-directed (PD-1-directed) immune checkpoint blockade results in durable antitumor activity in many advanced malignancies. Recent studies suggest that IFN-γ is a critical driver of programmed death ligand-1 (PD-L1) expression in cancer and host cells, and baseline intratumoral T cell infiltration may improve response likelihood to anti-PD-1 therapies, including pembrolizumab. However, whether quantifying T cell-inflamed microenvironment is a useful pan-tumor determinant of PD-1-directed therapy response has not been rigorously evaluated...
June 26, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28650053/in-situ-crystal-growth-of-gold-nanocrystals-on-upconversion-nanoparticles-for-synergistic-chemo-photothermal-therapy
#5
Ruoyan Wei, Wensong Xi, Haifang Wang, Jinliang Liu, Torsten Mayr, Liyi Shi, Lining Sun
A multifunctional cancer therapy nanocomposite was proposed and synthesized by linking the pH-responsive SH-PEG-DOX prodrug onto gold nanocrystals that were grown in situ on the surface of upconversion nanoparticles (UCNPs). In the structure of the SH-PEG-DOX prodrug, a hydrazone bond was utilized for subsequent pH-responsive drug release in the intracellular acidic microenvironment of cancer cells. This innovative assembly method is facile and mild, and can be used to obtain nanocomposites of UCNPs and gold, which show excellent photostability and biocompatibility...
June 26, 2017: Nanoscale
https://www.readbyqxmd.com/read/28649646/human-brain-metastatic-stroma-attracts-breast-cancer-cells-via-chemokines-cxcl16-and-cxcl12
#6
Brile Chung, Ali A Esmaeili, Sailesh Gopalakrishna-Pillai, John P Murad, Emily S Andersen, Naveen Kumar Reddy, Gayathri Srinivasan, Brian Armstrong, Caleb Chu, Young Kim, Tommy Tong, James Waisman, John H Yim, Behnam Badie, Peter P Lee
The tumor microenvironment is composed of heterogeneous populations of cells, including cancer, immune, and stromal cells. Progression of tumor growth and initiation of metastasis is critically dependent on the reciprocal interactions between cancer cells and stroma. Through RNA-Seq and protein analyses, we found that cancer-associated fibroblasts derived from human breast cancer brain metastasis express significantly higher levels of chemokines CXCL12 and CXCL16 than fibroblasts from primary breast tumors or normal breast...
2017: NPJ Breast Cancer
https://www.readbyqxmd.com/read/28649243/distinct-blood-and-visceral-adipose-tissue-regulatory-t-cell-and-innate-lymphocyte-profiles-characterize-obesity-and-colorectal-cancer
#7
Gloria Donninelli, Manuela Del Cornò, Marina Pierdominici, Beatrice Scazzocchio, Rosaria Varì, Barbara Varano, Ilenia Pacella, Silvia Piconese, Vincenzo Barnaba, Massimo D'Archivio, Roberta Masella, Lucia Conti, Sandra Gessani
Visceral adipose tissue (VAT) is a main site where metabolic and immunologic processes interplay to regulate, at local and systemic level, the inflammatory status and immune response. Obesity-associated inflammation and immune dysfunctions are inextricably linked to tumor but, in spite of intense efforts, the mechanisms underpinning this association remain elusive. In this report, we characterized the profile of VAT-associated and circulating innate lymphocyte and regulatory T (Treg) cell subsets underlying inflammatory conditions, such as obesity and colorectal cancer (CRC)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28648870/tlr7-and-tlr8-agonist-resiquimod-r848-differently-regulates-mif-expression-in-cells-and-organs
#8
Yao Mawulikplimi Adzavon, Pengxiang Zhao, Baobei Lv, Mengyu Liu, Xin Zhang, Fei Xie, Linqi Yang, Lei Shang, Mingzi Zhang, Qinjian Li, Xuemei Ma
Since its first description in 1966, macrophage migration inhibitory factor (MIF) was found to play a critical role in inflammatory and immune responses as well as in disease pathogenesis especially in tumor pathogenesis and cancer progression. MIF is expressed in different cell types and is associated with many disease severity and tumor pathogenesis. Here, we investigated the influence of TLR7 and TLR8 agonist resiquimod (R848), an immune response inducer used as a prophylactic agent for several infectious diseases as well as anticancer agents and vaccine adjuvant on MIF expression in cells and organs...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28648866/cytokines-in-immunogenic-cell-death-applications-for-cancer-immunotherapy
#9
REVIEW
Anne Showalter, Arati Limaye, Jeremiah L Oyer, Robert Igarashi, Christina Kittipatarin, Alicja J Copik, Annette R Khaled
Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions...
June 22, 2017: Cytokine
https://www.readbyqxmd.com/read/28648487/development-of-novel-avenues-to-overcome-challenges-facing-car-t-cells
#10
REVIEW
Soyeon Kim, Edmund K Moon
There has been dramatic success in treating patients with adoptive transfer of autologous T cells genetically modified to express a chimeric antigen receptor redirecting them to the antigen CD19. Despite this success, the application of chimeric antigen receptor T-cell therapy in solid malignancies has encountered many challenges that need to be overcome if similar success across other cancers is to become a reality. These challenges can be classified into 6 categories: the heterogeneity of tumor cell clones and tumor-associated antigen expression; poor T-cell trafficking into the tumor site; poor T-cell survival and persistence; the presence of suppressive immune cells; the secretion of suppressive soluble factors in the tumor microenvironment; and the upregulation of T-cell intrinsic inhibitory pathways...
June 10, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28647611/autophagy-suppresses-isoprenaline-induced-m2-macrophage-polarization-via-the-ros-erk-and-mtor-signaling-pathway
#11
Meihua Shan, Junfang Qin, Fengjiao Jin, Xiao Han, Haitao Guan, Xiaoge Li, Jiahui Zhang, Hongyao Zhang, Yue Wang
The objective of this study was to examine the effect of autophagy on stress-induced M2 macrophage polarization in the tumor microenvironment of breast cancer and to determine whether the underlying mechanism was related to the reactive oxygen species (ROS)/ERK and mTOR pathway. In vitro, we found that the basal autophagy level in mouse RAW 264.7 macrophages decreased with the incubation of tumor cell culture supernatant. Similarly, the polarization of RAW 264.7 to M2 macrophages was inhibited by the autophagy inducer rapamycin and increased by the autophagy inhibitor 3-MA or by siBeclin1...
June 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28647610/the-jak-stat3-axis-a-comprehensive-drug-target-for-solid-malignancies
#12
REVIEW
Jennifer Huynh, Nima Etemadi, Frédéric Hollande, Matthias Ernst, Michael Buchert
Intercellular communication between tumor cells, immune cells and the stroma characterises the tumor microenvironment, which is instrumental for establishing the ecological niche that fosters tumor growth and metastasis. While tumor cell intrinsic STAT3 signaling provides a crucial axis to support cell proliferation and survival, it also regulates many activities of the non-transformed cells that collectively make up the tumor microenvironment. Accordingly, excessive activation of STAT3 is a hallmark of many malignancies, and often occurs in response to cytokines of the IL-6 and IL-10 families...
June 21, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28646444/engineering-3d-models-of-tumors-and-bone-to-understand-tumor-induced-bone-disease-and-improve-treatments
#13
REVIEW
Kristin A Kwakwa, Joseph P Vanderburgh, Scott A Guelcher, Julie A Sterling
PURPOSE OF REVIEW: Bone is a structurally unique microenvironment that presents many challenges for the development of 3D models for studying bone physiology and diseases, including cancer. As researchers continue to investigate the interactions within the bone microenvironment, the development of 3D models of bone has become critical. RECENT FINDINGS: 3D models have been developed that replicate some properties of bone, but have not fully reproduced the complex structural and cellular composition of the bone microenvironment...
June 23, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28645612/il-1%C3%AE-induced-methylation-of-the-estrogen-receptor-er%C3%AE-gene-correlates-with-emt-and-chemoresistance-in-breast-cancer-cells
#14
Aura M Jiménez-Garduño, Mónica G Mendoza-Rodríguez, Daniel Urrutia-Cabrera, María C Domínguez-Robles, Eloy A Pérez-Yépez, Jorge Tonatiuh Ayala-Sumuano, Isaura Meza
Inflammation has been recently acknowledged as a key participant in the physiopathology of oncogenesis and tumor progression. The inflammatory cytokine IL-1β has been reported to induce the expression of markers associated with malignancy in breast cancerous cells through Epithelial-Mesenchymal Transition (EMT). Aggressive breast cancer tumors classified as Triple Negative do not respond to hormonal treatment because they lack three crucial receptors, one of which is the estrogen receptor alpha (ERα). Expression of ERα is then considered a good prognostic marker for tamoxifen treatment of this type of cancer, as the binding of this drug to the receptor blocks the transcriptional activity of the latter...
June 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28644558/current-understanding-of-cancer-stem-cells-review-of-their-radiobiology-and-role-in-head-and-neck-cancers
#15
REVIEW
Paul Ambrose Reid, Puthenparampil Wilson, Yanrui Li, Loredana Gabriela Marcu, Eva Bezak
Evidence of cancer cells that bear attributes analogous to those of normal stem cells has developed a hierarchical model of cancer's architecture and progression. This subset of cancer stem cells (CSCs) drives the progression and therapy resistance of cancers. Research to identify the phenotypes of these CSCs presents evidence of a subpopulation that is more resistant to therapy and may proliferate in response. Literature shows that CSCs typically represent around 1%-10% of cell populations in head and neck cancer but this proportion may increase in response to a therapeutic radiation dose...
June 23, 2017: Head & Neck
https://www.readbyqxmd.com/read/28644303/prostate-cancer-immunotherapy-the-path-forward
#16
Ravi A Madan, James L Gulley
PURPOSE OF REVIEW: To provide an overview of current strategies being investigated in the development of immunotherapy in prostate cancer. RECENT FINDINGS: Development of immunotherapy in prostate cancer actually began in 2010 with FDA approval of sipuleucel-T. Given that immune checkpoint inhibitor trials have either been negative at the phase III level or underwhelming in smaller studies, it is likely that combination strategies will be required to further maximize the impact immune-based therapies on the clinical course of the disease...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28643452/emerging-nanotechnology-and-advanced-materials-for-cancer-radiation-therapy
#17
REVIEW
Guosheng Song, Liang Cheng, Yu Chao, Kai Yang, Zhuang Liu
Radiation therapy (RT) including external beam radiotherapy (EBRT) and internal radioisotope therapy (RIT) has been widely used for clinical cancer treatment. However, owing to the low radiation absorption of tumors, high doses of ionizing radiations are often needed during RT, leading to severe damages to normal tissues adjacent to tumors. Meanwhile, the RT efficacies are limited by different mechanisms, among which the tumor hypoxia-associated radiation resistance is a well-known one, as there exists hypoxia inside most solid tumors while oxygen is essential to enhance radiation-induced DNA damages...
June 23, 2017: Advanced Materials
https://www.readbyqxmd.com/read/28642997/pd-1-and-cancer-molecular-mechanisms-and-polymorphisms
#18
REVIEW
Arash Salmaninejad, Vahid Khoramshahi, Alireza Azani, Ehsan Soltaninejad, Saeed Aslani, Mohammad Reza Zamani, Masoud Zal, Abolfazl Nesaei, Sayed Mostafa Hosseini
The programmed cell death protein 1 (PD-1) is expressed by activated T cells that act as an immunoregulatory molecule, and are responsible for the negative regulation of T cell activation and peripheral tolerance. The PD-1 gene also encodes an inhibitory cell surface receptor involved in the regulation of T cell functions during immune responses/tolerance. Beyond potent inhibitory effects on T cells, PD-1 also has a role in regulating B cell and monocyte responses. An overexpression of PD-1 has been reported to contribute to immune system avoidance in different cancers...
June 22, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28642603/imaging-of-anticancer-drug-action-in-single-cells
#19
REVIEW
Miles A Miller, Ralph Weissleder
Imaging is widely used in anticancer drug development, typically for whole-body tracking of labelled drugs to different organs or to assess drug efficacy through volumetric measurements. However, increasing attention has been drawn to pharmacology at the single-cell level. Diverse cell types, including cancer-associated immune cells, physicochemical features of the tumour microenvironment and heterogeneous cell behaviour all affect drug delivery, response and resistance. This Review summarizes developments in the imaging of in vivo anticancer drug action, with a focus on microscopy approaches at the single-cell level and translational lessons for the clinic...
June 23, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/28641961/wnt5a-and-its-signaling-pathway-in-angiogenesis
#20
REVIEW
Ya-Ning Shi, Neng Zhu, Chan Liu, Hong-Tao Wu, Yu Gui, Duan-Fang Liao, Li Qin
Wnt5a, a secreted glycoprotein, belongs to the noncanonical Wnt family involved in a wide range of organism development and tissue homeostasis. Wnt5a and its signaling pathway can regulate fundamental cellular processes, including specification of cell fate, proliferation, and survival. Accumulating evidence indicates that Wnt5a exhibits dual effects on angiogenesis. The formation of new blood vessels derives from pre-existing vessels via canonical and non-canonical Wnt pathways, depending on cell types, receptors, downstream effectors, and microenvironment...
June 20, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
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