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https://www.readbyqxmd.com/read/27893434/neuroinflammatory-and-cognitive-consequences-of-combined-radiation-and-immunotherapy-in-a-novel-preclinical-model
#1
Gwendolyn J McGinnis, David Friedman, Kristina H Young, Eileen Ruth S Torres, Charles R Thomas, Michael J Gough, Jacob Raber
BACKGROUND: Cancer patients often report behavioral and cognitive changes following cancer treatment. These effects can be seen in patients who have not yet received treatment or have received only peripheral (non-brain) irradiation. Novel treatments combining radiotherapy (RT) and immunotherapy (IT) demonstrate remarkable efficacy with respect to tumor outcomes by enhancing the proinflammatory environment in the tumor. However, a proinflammatory environment in the brain mediates cognitive impairments in other neurological disorders and may affect brain function in cancer patients receiving these novel treatments...
November 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27885577/distinct-expression-of-various-angiogenesis-factors-in-mice-brain-after-whole-brain-irradiation-by-x-ray
#2
Zhezhi Deng, Haiwei Huang, Xiaohong Wu, Mengmeng Wu, Guoyong He, Junjie Guo
Radiation-induced brain injury (RBI) is the most serious complication after radiotherapy. However, the etiology of RBI remains elusive. In order to evaluate the effect of X-rays on normal brain tissue, adult male BALB/C mice were subjected to whole-brain exposure with a single dose of 10 Gy or sham radiation. The structure and number of mice brain vessels were investigated 1, 7, 30, 90 and 180 days after irradiation by H&E staining and immune-fluorescence staining. Compared with sham control mice, in addition to morphological changes, a significant reduction of microvascular density was detected in irradiated mice brains...
November 25, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27864061/melanogenesis-inhibits-respiration-in-b16-f10-melanoma-cells-whereas-enhances-mitochondrial-cell-content
#3
Willian Vanderlei Meira, Tassiele Andréa Heinrich, Silvia Maria Suter Correia Cadena, Glaucia Regina Martinez
Melanoma is a rare and aggressive skin tumor; the survival of patients diagnosed late is fairly low. This high mortality rate is due to the characteristics of the cells that allow them to be resistant to radiotherapy and conventional chemotherapy, besides of being able to evade the immune system. Melanin, the pigment responsible for skin, hair and eye color, seems to be involved in this resistance. The main function of melanin is to protect the cells against ultraviolet (UV) light by absorbing this radiation and reactive oxygen species (ROS) scavenging...
November 15, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27825048/the-effect-of-the-tlr9-ligand-cpg-oligodeoxynucleotide-on-the-protective-immune-response-to-radiation-induced-lung-fibrosis-in-mice
#4
Jing Chen, Xiaoli Tian, Zijie Mei, Yacheng Wang, Ye Yao, Shimin Zhang, Xin Li, Hui Wang, Junhong Zhang, Conghua Xie
CpG-oligodeoxynucleotide (CpG-ODN) is not only reported to protect against airway hyper responsiveness but is also known as a potent vaccine adjuvant for anti-tumor therapy. Little is known about the effect of CpG-ODN in mice with radiation-induced lung fibrosis (RILF), a common late stage form of tissue damage that occurs after thorax radiotherapy (RT). Here, we evaluated the immunomodulatory effects of CpG-ODN on the development of RILF. Mice were divided into four groups: (1) RT, single dose of 12Gy to the whole thorax; (2) CpG, only intraperitoneal injection of CpG-ODN for total 5 weeks; (3) RT+CpG, irradiation plus CpG-ODN treatment before and after irradiation for total 5 weeks; and (4) control (CTL): No RT or CpG-ODN treatment...
November 5, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27813697/radioprotective-effect-of-green-tea-and-grape-seed-extracts-mixture-on-gamma-irradiation-induced-immune-suppression-in-male-albino-rats
#5
W El-Desouky, A H Mahmoud, M M Abbas
: Green tea extract (GTE) and grape seed extract (GSE) have antioxidant and radioprotective effects. The current study aimed to investigate the radioprotective effect of GTE and GSE mixture on radiation induced immune suppression in rats. METHOD: 35 male albino rats were divided into five groups: group 1 (control rats). The 2(nd) and 3(rd) groups rats were exposed to a single dose of gamma radiation (5 and 10Gy) respectively. The 4(th) and 5(th) groups of rats were gamma irradiated with 5 and 10Gy respectively, then administrated by gavage with GTE and GSE mixture (100 mg: 200 mg/kg B...
November 4, 2016: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/27764686/concurrent-irradiation-with-the-anti-programmed-cell-death-ligand-1-immune-checkpoint-blocker-durvalumab-single-centre-subset-analysis-from-a-phase-1-2-trial
#6
Antonin Levy, Christophe Massard, Jean-Charles Soria, Eric Deutsch
PURPOSE: To assess preliminary safety and efficacy results of the anti-programmed cell death ligand-1 (anti-PD-L1) durvalumab in combination with radiotherapy (RT) in an expansion cohort of patients included in a phase 1/2 trial at our institution. PATIENTS AND METHODS: Data from patients who received concurrent palliative RT with durvalumab (10 mg/kg every 2 weeks via intravenous infusion) were analysed in terms of safety (CTCAE v4.0) and efficacy (RECIST v1.1 and tumour growth rate [TGR])...
November 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/27743027/rationale-and-evidence-to-combine-radiation-therapy-and-immunotherapy-for-cancer-treatment
#7
Dan Ishihara, Laurentiu Pop, Tsuguhide Takeshima, Puneeth Iyengar, Raquibul Hannan
Cancer immunotherapy exploits the immune system's ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT)...
October 14, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/27722125/radiation-induced-immune-responses-mechanisms-and-therapeutic-perspectives
#8
Hoibin Jeong, Seoyeon Bok, Beom-Ju Hong, Hyung-Seok Choi, G-One Ahn
Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation...
September 2016: Blood Research
https://www.readbyqxmd.com/read/27662339/radiotherapy-to-control-limited-melanoma-progression-following-ipilimumab
#9
Lauren M Kropp, Jennifer F De Los Santos, Svetlana B McKee, Robert M Conry
Durable local control of irradiated cancer and distant abscopal effects are presumably immune mediated. To evaluate the role of radiotherapy (RT) for limited progression after anti-CTLA4 checkpoint inhibition, medical records of all patients with surgically incurable stage III or IV melanoma from a single institution who received ipilimumab as first-line immunotherapy and subsequent RT were reviewed. Sixteen patients who received RT to all sites of limited melanoma progression were analyzed. Eight patients with an incomplete initial response to ipilimumab received RT to new or progressive disease, whereas the remaining 8 patients with a complete initial response to ipilimumab received RT to sites of subsequent recurrence...
November 2016: Journal of Immunotherapy
https://www.readbyqxmd.com/read/27660472/the-clinical-effects-of-low-dose-splenic-irradiation-combined-with-chest-three-dimensional-conformal-radiotherapy-on-patients-with-locally-advanced-non-small-cell-lung-cancer-a-randomized-clinical-trial
#10
Hongsheng Yu, Yong Qu, Qingjun Shang, Chao Yan, Peng Jiang, Xiang Wang, Donghai Liang, Tao Jiang
OBJECTIVE: The objective of this study was to explore the clinical effects of low-dose splenic irradiation on locally advanced non-small-cell lung cancer (NSCLC) patients. METHODS: Thirty-eight patients with stage III NSCLC were randomly divided into a control group and a combined treatment group. The control group only received chest three-dimensional conformal radiotherapy, while the combined treatment group received low-dose splenic irradiation followed by chest three-dimensional conformal radiotherapy after 6 hours...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27550452/abscopal-effects-of-radiotherapy-are-enhanced-by-combined-immunostimulatory-mabs-and-are-dependent-on-cd8-t-cells-and-crosspriming
#11
María E Rodriguez-Ruiz, Inmaculada Rodriguez, Saray Garasa, Benigno Barbes, Jose Luis Solorzano, Jose Luis Perez-Gracia, Sara Labiano, Miguel F Sanmamed, Arantza Azpilikueta, Elixabet Bolaños, Alfonso R Sanchez-Paulete, M Angela Aznar, Ana Rouzaut, Kurt A Schalper, Maria Jure-Kunkel, Ignacio Melero
Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments...
October 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27513864/intricate-macrophage-colorectal-cancer-cell-communication-in-response-to-radiation
#12
Ana T Pinto, Marta L Pinto, Sérgia Velho, Marta T Pinto, Ana P Cardoso, Rita Figueira, Armanda Monteiro, Margarida Marques, Raquel Seruca, Mário A Barbosa, Marc Mareel, Maria J Oliveira, Sónia Rocha
Both cancer and tumour-associated host cells are exposed to ionizing radiation when a tumour is subjected to radiotherapy. Macrophages frequently constitute the most abundant tumour-associated immune population, playing a role in tumour progression and response to therapy. The present work aimed to evaluate the importance of macrophage-cancer cell communication in the cellular response to radiation. To address this question, we established monocultures and indirect co-cultures of human monocyte-derived macrophages with RKO or SW1463 colorectal cancer cells, which exhibit higher and lower radiation sensitivity, respectively...
2016: PloS One
https://www.readbyqxmd.com/read/27427766/fractionated-radiotherapy-with-3-x-8-gy-induces-systemic-anti-tumour-responses-and-abscopal-tumour-inhibition-without-modulating-the-humoral-anti-tumour-response
#13
Thomas H P M Habets, Tammy Oth, Ans W Houben, Mirelle J A J Huijskens, Birgit L M G Senden-Gijsbers, Melanie C A Schnijderberg, Boudewijn Brans, Ludwig J Dubois, Philippe Lambin, Marijke De Saint-Hubert, Wilfred T V Germeraad, Marcel G J Tilanus, Felix M Mottaghy, Gerard M J Bos, Joris Vanderlocht
Accumulating evidence indicates that fractionated radiotherapy (RT) can result in distant non-irradiated (abscopal) tumour regression. Although preclinical studies indicate the importance of T cells in this infrequent phenomenon, these studies do not preclude that other immune mechanisms exhibit an addition role in the abscopal effect. We therefore addressed the question whether in addition to T cell mediated responses also humoral anti-tumour responses are modulated after fractionated RT and whether systemic dendritic cell (DC) stimulation can enhance tumour-specific antibody production...
2016: PloS One
https://www.readbyqxmd.com/read/27356059/investigation-of-abscopal-and-bystander-effects-in-immunocompromised-mice-after-exposure-to-pencilbeam-and-microbeam-synchrotron-radiation
#14
Cristian Fernandez-Palomo, Elisabeth Schültke, Elke Bräuer-Krisch, Jean Albert Laissue, Hans Blattmann, Colin Seymour, Carmel Mothersill
Out-of-field effects are of considerable interest in radiotherapy. The mechanisms are poorly understood but are thought to involve signaling processes, which induce responses in non-targeted cells and tissues. The immune response is thought to play a role. The goal of this research was to study the induction of abscopal effects in the bladders of NU-Foxn1 mice after irradiating their brains using Pencil Beam (PB) or microbeam (MRT) irradiation at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France...
August 2016: Health Physics
https://www.readbyqxmd.com/read/27302167/mathematical-modeling-of-cancer-immunotherapy-and-its-synergy-with-radiotherapy
#15
Raphael Serre, Sebastien Benzekry, Laetitia Padovani, Christophe Meille, Nicolas André, Joseph Ciccolini, Fabrice Barlesi, Xavier Muracciole, Dominique Barbolosi
Combining radiotherapy with immune checkpoint blockade may offer considerable therapeutic impact if the immunosuppressive nature of the tumor microenvironment (TME) can be relieved. In this study, we used mathematical models, which can illustrate the potential synergism between immune checkpoint inhibitors and radiotherapy. A discrete-time pharmacodynamic model of the combination of radiotherapy with inhibitors of the PD1-PDL1 axis and/or the CTLA4 pathway is described. This mathematical framework describes how a growing tumor first elicits and then inhibits an antitumor immune response...
September 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27302161/checkpoint-antibodies-but-not-t-cell-recruiting-diabodies-effectively-synergize-with-til-inducing-%C3%AE-irradiation
#16
Michael Hettich, Jayashree Lahoti, Shruthi Prasad, Gabriele Niedermann
T cell-recruiting bispecific antibodies (bsAb) show promise in hematologic malignancies and are also being evaluated in solid tumors. In this study, we investigated whether T cell-recruiting bsAbs synergize with hypofractionated tumor radiotherapy (hRT) and/or blockade of the programmed death-1 (PD-1) immune checkpoint, both of which can increase tumor-infiltrating lymphocyte (TIL) numbers. Unexpectedly, large melanomas treated with hRT plus bsAb (AC133×CD3) relapsed faster than those treated with hRT alone, accompanied by massive TIL apoptosis...
August 15, 2016: Cancer Research
https://www.readbyqxmd.com/read/27252074/the-chinese-herbal-mixture-tien-hsien-liquid-augments-the-anticancer-immunity-in-tumor-cell-vaccinated-mice
#17
Pei-Ming Yang, Jia-Ling Du, George Nian-Kae Wang, Jean-San Chia, Wei-Bin Hsu, Pin-Ching Pu, Andy Sun, Chun-Pin Chiang, Won-Bo Wang
Background The Chinese herbal mixture, Tien-Hsien liquid (THL), has been used as an anticancer dietary supplement for more than 20 years. Our previous studies have shown that THL can modulate immune responseand inhibit tumor growth. In this study, we further evaluated the effect of THL on anticancer immune response in mice vaccinated with γ-ray-irradiated tumor cells. Methods The antitumor effect of THL was determined in mice vaccinated with low-tumorigenic CT-26-low colon cancer cells or γ-ray-irradiated high-tumorigenic CT-26-high colon cancer cells...
June 1, 2016: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/27190630/can-abscopal-effects-of-local-radiotherapy-be-predicted-by-modeling-t-cell-trafficking
#18
Sandra Demaria, Silvia C Formenti
The abscopal effect of radiation describes tumor regression in metastases outside of the field upon treatment of one site, and is mediated by radiation-induced anti-tumor T cells. The ability of radiation to generate an in situ tumor vaccine and improve responses to immunotherapy is under intense investigation in the clinic. Preclinical and clinical evidence shows that multiple factors regulate radiation interaction with the immune system within and outside of the irradiated tumor. Poleszczuk and colleagues developed a mathematical model of T cell trafficking between metastases, and in a recent publication propose that the specific metastatic site irradiated determines the ability of T cells to traffic to other metastases and mediate abscopal responses and should dictate clinical decision making [Poleszczuk et al...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/27144583/regulatory-t-cells-contribute-to-the-inhibition-of-radiation-induced-acute-lung-inflammation-via-bee-venom-phospholipase-a%C3%A2-in-mice
#19
Dasom Shin, Gihyun Lee, Sung-Hwa Sohn, Soojin Park, Kyung-Hwa Jung, Ji Min Lee, Jieun Yang, Jaeho Cho, Hyunsu Bae
Bee venom has long been used to treat various inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis. Previously, we reported that bee venom phospholipase A₂ (bvPLA₂) has an anti-inflammatory effect through the induction of regulatory T cells. Radiotherapy is a common anti-cancer method, but often causes adverse effects, such as inflammation. This study was conducted to evaluate the protective effects of bvPLA₂ in radiation-induced acute lung inflammation. Mice were focally irradiated with 75 Gy of X-rays in the lung and administered bvPLA₂ six times after radiation...
2016: Toxins
https://www.readbyqxmd.com/read/27113815/immunomodulation-of-classical-and-non-classical-hla-molecules-by-ionizing-radiation
#20
REVIEW
Cristina E Gallegos, Severino Michelin, Diana Dubner, Edgardo D Carosella
Radiotherapy has been employed for the treatment of oncological patients for nearly a century, and together with surgery and chemotherapy, radiation oncology constitutes one of the three pillars of cancer therapy. Ionizing radiation has complex effects on neoplastic cells and on tumor microenvironment: beyond its action as a direct cytotoxic agent, tumor irradiation triggers a series of alterations in tumoral cells, which includes the de novo synthesis of particular proteins and the up/down-regulation of cell surface molecules...
May 2016: Cellular Immunology
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