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https://www.readbyqxmd.com/read/29309266/radiation-induced-long-noncoding-rnas-in-a-mouse-model-after-whole-body-irradiation
#1
Molykutty J Aryankalayil, Sunita Chopra, Joel Levin, Iris Eke, Adeola Makinde, Shaoli Das, Uma Shankavaram, Claire Vanpouille-Box, Sandra Demaria, C Norman Coleman
Long noncoding RNAs (lncRNAs) are emerging as key molecules in regulating many biological processes and have been implicated in development and disease pathogenesis. Biomarkers of cancer and normal tissue response to treatment are of great interest in precision medicine, as well as in public health and medical management, such as for assessment of radiation injury after an accidental or intentional exposure. Circulating and functional RNAs, including microRNAs (miRNAs) and lncRNAs, in whole blood and other body fluids are potential valuable candidates as biomarkers...
January 8, 2018: Radiation Research
https://www.readbyqxmd.com/read/29284398/mechanisms-of-radiation-bystander-and-non-targeted-effects-implications-to-radiation-carcinogenesis-and-radiotherapy
#2
Rasoul Yahyapour, Elahe Motevaseli, Abolhasan Rezaeyan, Hamid Abdollahi, Bagher Farhood, Mohsen Cheki, Masoud Najafi, Vilmar Villa
Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remain to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence...
December 29, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29258856/emerging-biomarkers-for-the-combination-of-radiotherapy-and-immune-checkpoint-blockers
#3
REVIEW
Claire Lhuillier, Claire Vanpouille-Box, Lorenzo Galluzzi, Silvia Chiara Formenti, Sandra Demaria
Over the past few years, multiple immune checkpoint blockers (ICBs) have achieved unprecedented clinical success and have been approved by regulatory agencies for the treatment of an increasing number of malignancies. However, only a limited fraction of patients responds to ICBs employed as a standalone intervention, calling for the development of combinatorial regimens. Radiation therapy (RT) stands out as a very promising candidate for this purpose. Indeed, RT mediates antineoplastic effects not only by cytotoxic and cytostatic mechanisms, but also by modulating immunological functions, both locally (within the irradiated field) and systemically...
December 16, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29247829/pd-1-modulates-radiation-induced-cardiac-toxicity-through-cytotoxic-t-lymphocytes
#4
Shisuo Du, Lin Zhou, Gregory S Alexander, Kyewon Park, Lifeng Yang, Nadan Wang, Xinliang Ma, Yajing Wang, Adam P Dicker, Bo Lu
INTRODUCTION: Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-PD1 drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with HD and breast cancer...
December 13, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29198327/critical-features-and-challenges-associated-with-imaging-in-patients-undergoing-cancer-immunotherapy
#5
REVIEW
Cinzia Solinas, Michele Porcu, Zuzana Hlavata, Pushpamali De Silva, Marco Puzzoni, Karen Willard-Gallo, Mario Scartozzi, Luca Saba
Manipulating an individual's immune system through immune checkpoint blockade is revolutionizing the paradigms of cancer treatment. Peculiar patterns and kinetics of response have been observed with these new drugs, rendering the assessment of tumor burden particularly challenging in cancer immunotherapy. The mechanisms of action for immune checkpoint blockade, based upon engagement of the adaptive immune system, can generate unusual response patterns, including pseudoprogression, hyperprogression, atypical and delayed responses...
December 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29170400/host-sting-dependent-mdsc-mobilization-drives-extrinsic-radiation-resistance
#6
Hua Liang, Liufu Deng, Yuzhu Hou, Xiangjiao Meng, Xiaona Huang, Enyu Rao, Wenxin Zheng, Helena Mauceri, Matthias Mack, Meng Xu, Yang-Xin Fu, Ralph R Weichselbaum
Radiotherapy induces and promotes innate and adaptive immunity in which host STING plays an important role. However, radioresistance in irradiated tumors can also develop, resulting in relapse. Here we report a mechanism by which extrinsic resistance develops after local ablative radiation that relies on the immunosuppressive action of STING. The STING/type I interferon pathway enhances suppressive inflammation in tumors by recruiting myeloid cells in part via the CCR2 pathway. Germ-line knockouts of CCR2 or treatment with an anti-CCR2 antibody results in blockade of radiation-induced MDSC infiltration...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163540/local-high-dose-radiotherapy-induces-systemic-immunomodulating-effects-of-potential-therapeutic-relevance-in-oligometastatic-breast-cancer
#7
Elena Muraro, Carlo Furlan, Michele Avanzo, Debora Martorelli, Elisa Comaro, Aurora Rizzo, Damiana A Fae', Massimiliano Berretta, Loredana Militello, Alessandro Del Conte, Simon Spazzapan, Riccardo Dolcetti, Marco Trovo'
Local irradiation of cancer through radiotherapy can induce spontaneous regression of non-directly irradiated lesions, suggesting the involvement of systemic antitumor immune responses. In oligometastatic breast cancer (BC) patients, the use of stereotactic body radiotherapy (SBRT) favors the local control of treated lesions and may contribute to break local tolerance and release tumor-associated antigens (TAAs), improving host antitumor immunity. We performed a detailed immunomonitoring of BC patients undergoing SBRT to verify its ability to "switch on" the anti-tumor immunity both systemically, in peripheral blood, and locally, employing in vitro BC models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29162646/nkg2d-dependent-anti-tumor-effects-of-chemotherapy-and-radiotherapy-against-glioblastoma
#8
Tobias Weiss, Hannah Schneider, Manuela Silginer, Alexander Steinle, Martin N Pruschy, Bojan Polic, Michael Weller, Patrick Roth
PURPOSE: NKG2D is a potent activating immune cell receptor and glioma cells express the cognate ligands (NKG2DL). These ligands are inducible by cellular stress and temozolomide (TMZ) or irradiation (IR), the standard treatment of glioblastoma, could affect their expression. However, a role of NKG2DL for the efficacy of TMZ and IR has never been addressed. EXPERIMENTAL DESIGN: We assessed the effect of TMZ and IR on NKG2DL in vitro and in vivo in a variety of murine and human glioblastoma models including glioma-initiating cells and a cohort of paired glioblastoma samples from patients before and after therapy...
November 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29138841/enhanced-activated-t%C3%A2-cell-subsets-in-prostate-cancer-patients-receiving-iodine-125-low-dose-rate-prostate-brachytherapy
#9
Makoto Kubo, Takefumi Satoh, Hiromichi Ishiyama, Ken-Ichi Tabata, Hideyasu Tsumura, Shoko Komori, Masatsugu Iwamura, Shiro Baba, Kazushige Hayakawa, Toshihiko Kawamura, Fumiya Obata
Radiotherapy (RT) is one of the most important treatments for prostate cancer. Although RT can kill cancer cells through direct and indirect effects of radiation, it occasionally induces an abscopal effect whereby localized radiation treatment is associated with elimination of metastatic cancer at a distance from the irradiated area. Thus, RT may induce an effective antitumor immune response, although the mechanism involved has remained unclear. The present was designed to evaluate this effect of RT in 36 patients with prostate cancer who provided informed consent prior to enrollment in this clinical trial...
November 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29119941/targeting-of-inflammation-for-radiation-protection-and-mitigation
#10
Rasoul Yahyapour, Peyman Amini, Saeed Rezapoor, Abolhasan Rezaeyan, Bagher Farhood, Mohsen Cheki, Hengameh Fallah, Masoud Najafi
Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect...
November 8, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29113972/localized-synchrotron-irradiation-of-mouse-skin-induces-persistent-systemic-genotoxic-and-immune-responses
#11
Jessica Ventura, Pavel N Lobachevsky, Jason S Palazzolo, Helen Forrester, Nicole M Haynes, Alesia Ivashkevich, Andrew W Stevenson, Christopher J Hall, Andreas Ntargaras, Vasilis Kotsaris, Gerasimos Ch Pollakis, Gianna Potsi, Konstantinos Skordylis, Georgia Terzoudi, Ioannis S Pateras, Vassilis G Gorgoulis, Alexandros G Georgakilas, Carl N Sprung, Olga A Martin
The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses...
November 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29113340/analgecine-enhances-the-anti-tumor-response-of-radiotherapy-by-increasing-apoptosis-and-cell-cycle-arrest-in-non-small-cell-lung-cancer
#12
Xue Chen, Xibing Zhuang, Qi Zhang, Youjun Luo, Sujuan Yuan, Tiankui Qiao
We investigated whether Analgecine treatment enhanced the antitumor response of radiotherapy in non-small cell lung cancer (NSCLC) cells. Lewis lung carcinoma (LLC) xenograft mice treated with Analgecine plus irradiation showed reduced tumor growth and increased survival. Tumor cell apoptosis was enhanced by Analgecine, based on TUNEL assays. It also increased plasma levels of pro-inflammatory cytokines (IL-6, IL-12, and IFN-γ) and decreased anti-inflammatory cytokines (TGFβ and IL-10), suggesting an enhanced immune response...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108250/local-irradiation-does-not-enhance-the-effect-of-immunostimulatory-adcd40l-gene-therapy-combined-with-low-dose-cyclophosphamide-in-melanoma-patients
#13
Sandra Irenaeus, Aglaia Schiza, Sara M Mangsbo, Jessica Wenthe, Emma Eriksson, Johan Krause, Anders Sundin, Håkan Ahlström, Thomas H Tötterman, Angelica Loskog, Gustav J Ullenhag
Background: AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy. Methods: AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100279/radiotherapy-prolongs-the-survival-of-advanced-non-small-cell-lung-cancer-patients-undergone-to-an-immune-modulating-treatment-with-dose-fractioned-cisplatin-and-metronomic-etoposide-and-bevacizumab-mpebev
#14
Pierpaolo Pastina, Valerio Nardone, Cirino Botta, Stefania Croci, Paolo Tini, Giuseppe Battaglia, Veronica Ricci, Maria Grazia Cusi, Claudia Gandolfo, Gabriella Misso, Silvia Zappavigna, Michele Caraglia, Antonio Giordano, Donatella Aldinucci, Pierfrancesco Tassone, Pierosandro Tagliaferri, Luigi Pirtoli, Pierpaolo Correale
Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growth-factor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042994/immunological-mechanism-of-low-dose-priming-radiation-resistance-in-walker-256-tumor-model-mice
#15
Li Feng, Ling Qin, Dan Guo, Daping Deng, Feng Lu, Hailiang Li, Narisu Bao, Xiting Yang, Hongyu Ding, Jianguo Li
The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29027221/abscopal-immunological-effects-of-radiotherapy-narrowing-the-gap-between-clinical-and-preclinical-experiences
#16
REVIEW
Nikko Brix, Anna Tiefenthaller, Heike Anders, Claus Belka, Kirsten Lauber
Radiotherapy-despite being a local therapy that meanwhile is characterized by an impressively high degree of spatial accuracy-can stimulate systemic phenomena which occasionally lead to regression and rejection of non-irradiated, distant tumor lesions. These abscopal effects of local irradiation have been observed in sporadic clinical case reports since the beginning of the 20th century, and extensive preclinical work has contributed to identify systemic anti-tumor immune responses as the underlying driving forces...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28987882/radiation-enhanced-delivery-of-systemically-administered-amphiphilic-cpg-oligodeoxynucleotide
#17
Oliver K Appelbe, Kelly D Moynihan, Amy Flor, Nick Rymut, Darrell J Irvine, Stephen J Kron
Along with vaccines and checkpoint blockade, immune adjuvants may have an important role in tumor immunotherapy. Oligodeoxynucleotides containing unmethylated cytidyl guanosyl dinucleotide motifs (CpG ODN) are TLR9 ligands with attractive immunostimulatory properties, but intratumoral administration has been required to induce an effective anti-tumor immune response. Following on recent studies with radiation-targeted delivery of nanoparticles, we examined enhanced tumor-specific delivery of amphiphile-CpG, an albumin-binding analog of CpG ODN, following systemic administration 3days after tumor irradiation...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28970196/stereotactic-radiotherapy-increases-functionally-suppressive-regulatory-t-cells-in-the-tumor-microenvironment
#18
Yuki Muroyama, Thomas R Nirschl, Christina M Kochel, Zoila Lopez-Bujanda, Debebe Theodros, Wendy Mao, Maria A Carrera-Haro, Ali Ghasemzadeh, Ariel E Marciscano, Esteban Velarde, Ada J Tam, Christopher J Thoburn, Muniza Uddin, Alan K Meeker, Robert A Anders, Drew M Pardoll, Charles G Drake
Radiotherapy (RT) enhances innate and adaptive antitumor immunity; however, the effects of radiation on suppressive immune cells, such as regulatory T cells (Treg), in the tumor microenvironment (TME) are not fully elucidated. Although previous reports suggest an increased Treg infiltration after radiation, whether these Tregs are functionally suppressive remains undetermined. To test the hypothesis that RT enhances the suppressive function of Treg in the TME, we selectively irradiated implanted tumors using the small animal radiation research platform (SARRP), which models stereotactic radiotherapy in human patients...
October 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#19
Hannah Tharmalingam, Peter J Hoskin
In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916224/lack-of-differences-in-radiation-induced-immunogenicity-parameters-between-hpv-positive-and-hpv-negative-human-hnscc-cell-lines
#20
Karolin Schneider, Vanesa Bol, Vincent Grégoire
BACKGROUND AND PURPOSE: Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines...
September 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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