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Irradiation or radiotherapy and immune

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https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#1
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
#2
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 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28912510/the-th1-th17-balance-dictates-the-fibrosis-response-in-murine-radiation-induced-lung-disease
#3
Alexandra Paun, Marie-Eve Bergeron, Christina K Haston
Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains were exposed to 18 Gy whole thorax irradiation and upon respiratory distress strains prone to pneumonitis with fibrosis presented an increased pulmonary frequency of Thelper (Th)17 cells which was not evident in strains prone solely to pneumonitis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858075/concurrent-radiotherapy-for-patients-with-metastatic-melanoma-and-receiving-anti-programmed-death-1-therapy-a-safe-and-effective-combination
#4
Amélie Aboudaram, Anouchka Modesto, Léonor Chaltiel, Carlos Gomez-Roca, Serge Boulinguez, Vincent Sibaud, Jean-Pierre Delord, Ciprian Chira, Martine Delannes, Elizabeth Moyal, Nicolas Meyer
A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28836991/modeling-dna%C3%A2-damage-induced-pneumopathy-in-mice-insight-from-danger-signaling-cascades
#5
REVIEW
Florian Wirsdörfer, Verena Jendrossek
Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secretory program. The resulting pro-inflammatory and pro-angiogenic microenvironment triggers a cascade of events that can lead within weeks to a pronounced lung inflammation (pneumonitis) or after months to excessive deposition of extracellular matrix molecules and tissue scarring (pulmonary fibrosis)...
August 24, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28791251/combining-oncolytic-adenovirus-with-radiation-a-paradigm-for-the-future-of-radiosensitization
#6
REVIEW
Sean M O'Cathail, Tzveta D Pokrovska, Timothy S Maughan, Kerry D Fisher, Leonard W Seymour, Maria A Hawkins
Oncolytic viruses and radiotherapy represent two diverse areas of cancer therapy, utilizing quite different treatment modalities and with non-overlapping cytotoxicity profiles. It is, therefore, an intriguing possibility to consider that oncolytic ("cancer-killing") viruses may act as cancer-selective radiosensitizers, enhancing the therapeutic consequences of radiation treatment on tumors while exerting minimal effects on normal tissue. There is a solid mechanistic basis for this potential synergy, with many viruses having developed strategies to inhibit cellular DNA repair pathways in order to protect themselves, during genome replication, from unwanted interference by cell processes that are normally triggered by DNA damage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28791250/immunotherapy-combined-with-large-fractions-of-radiotherapy-stereotactic-radiosurgery-for-brain-metastases-implications-for-intraoperative-radiotherapy-after-resection
#7
REVIEW
Carsten Herskind, Frederik Wenz, Frank A Giordano
Brain metastases (BM) affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS) while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT) to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#8
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28739315/combination-therapy-of-radiotherapy-and-anti-pd-1-pd-l1-treatment-in-non-small-cell-lung-cancer-a-mini-review
#9
REVIEW
Shinkichi Takamori, Gouji Toyokawa, Kazuki Takada, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28714110/poly-vinylpyrollidone-and-selenocysteine-modified-bi2-se3-nanoparticles-enhance-radiotherapy-efficacy-in-tumors-and-promote-radioprotection-in-normal-tissues
#10
Jiangfeng Du, Zhanjun Gu, Liang Yan, Yuan Yong, Xuan Yi, Xiao Zhang, Jing Liu, Renfei Wu, Cuicui Ge, Chunying Chen, Yuliang Zhao
The development of a new generation of nanoscaled radiosensitizers that can not only enhance radiosensitization of tumor tissues, but also increase radioresistance of healthy tissue is highly desirable, but remains a great challenge. Here, this paper reports a new versatile theranostics based on poly(vinylpyrollidone)- and selenocysteine-modified Bi2 Se3 nanoparicles (PVP-Bi2 Se3 @Sec NPs) for simultaneously enhancing radiotherapeutic effects and reducing the side-effects of radiation. The as-prepared nanoparticles exhibit significantly enhanced free-radical generation upon X-ray radiation, and remarkable photothermal effects under 808 nm NIR laser irradiation because of their strong X-ray attenuation ability and high NIR absorption capability...
September 2017: Advanced Materials
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#11
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28686531/microenvironment-and-dose-delivery-dependent-response-after-exposure-to-ionizing-radiation-in-human-colorectal-cancer-cell-lines
#12
Vaidotas Stankevicius, Gintautas Vasauskas, Ryte Rynkeviciene, Jonas Venius, Vita Pasukoniene, Eduardas Aleknavicius, Kestutis Suziedelis
A significant body of knowledge about radiobiology is based on studies of single dose cellular irradiation, despite the fact that conventional clinical applications using dose fractionation. In addition, cellular radiation response strongly depends on cell-cell and cell-extracellular matrix (ECM) interactions, which are poorly established in cancer cells grown under standard 2D cell culture conditions. In this study, we investigated the response of human colorectal carcinoma (CRC) DLD1 and HT29 cell lines, bearing distinct p53 mutations, to a single 2 or 10 Gy dose or fractionated 5 × 2 Gy doses of radiation using global transcriptomics analysis...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28671677/effects-of-proton-versus-photon-irradiation-on-lymph-angiogenic-inflammatory-proliferative-and-anti-tumor-immune-responses-in-head-and-neck-squamous-cell-carcinoma
#13
M Lupu-Plesu, A Claren, S Martial, P-D N'Diaye, K Lebrigand, N Pons, D Ambrosetti, I Peyrottes, J Feuillade, J Hérault, M Dufies, J Doyen, G Pagès
The proximity of organs at risk makes the treatment of head and neck squamous cell carcinoma (HNSCC) challenging by standard radiotherapy. The higher precision in tumor targeting of proton (P) therapy could promote it as the treatment of choice for HNSCC. Besides the physical advantage in dose deposition, few is known about the biological impact of P versus photons (X) in this setting. To investigate the comparative biological effects of P versus X radiation in HNSCC cells, we assessed the relative biological effectiveness (RBE), viability, proliferation and mRNA levels for genes involved in (lymph)angiogenesis, inflammation, proliferation and anti-tumor immunity...
July 3, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28661901/long-term-and-late-treatment-consequences-endocrine-and-metabolic-effects
#14
Thang S Han, Helena K Gleeson
PURPOSE OF REVIEW: Cancer therapies often result in the 'late effect of cancer treatment' whereby secondary health complications emerge years after radiotherapy and chemotherapy. This review focuses on endocrine and metabolic consequences in adult cancer survivors as late treatment effects. RECENT FINDINGS: Endocrine and metabolic disorders are among the most common late effects. Endocrine disorders include hypopituitarism, which leads to growth hormone deficiency, hypogonadism, adrenal insufficiency and hypothyroidism and related clinical manifestations...
September 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28638385/intercellular-communication-of-tumor-cells-and-immune-cells-after-exposure-to-different-ionizing-radiation-qualities
#15
REVIEW
Sebastian Diegeler, Christine E Hellweg
Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28598415/dna-exonuclease-trex1-regulates-radiotherapy-induced-tumour-immunogenicity
#16
Claire Vanpouille-Box, Amandine Alard, Molykutty J Aryankalayil, Yasmeen Sarfraz, Julie M Diamond, Robert J Schneider, Giorgio Inghirami, C Norman Coleman, Silvia C Formenti, Sandra Demaria
Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol upon radiation. Cytosolic DNA stimulates secretion of interferon-β by cancer cells following activation of the DNA sensor cGAS and its downstream effector STING...
June 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28558844/radiation-related-lymphopenia-is-associated-with-spleen-irradiation-dose-during-radiotherapy-in-patients-with-hepatocellular-carcinoma
#17
Jing Liu, Qianqian Zhao, Weiye Deng, Jie Lu, Xiaoqing Xu, Renben Wang, Xia Li, Jinbo Yue
BACKGROUND: The decrease in peripheral blood lymphocytes induced by radiation lessens the antitumour effect of the immune response, which might cause immunosuppression. We aimed to investigate the correlation between the decrease in peripheral blood lymphocytes during radiotherapy (RT) and the spleen irradiation dose in patients with hepatocellular carcinoma (HCC). METHODS: The subjects were 59 patients with HCC who had received RT from 2005 to 2014. The Min ALC (minimum value of absolute counts for peripheral blood lymphocytes) was collected from the routine workup for each patient prior to RT and weekly during RT...
May 30, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28539271/gene-expression-profiling-of-tumor-associated-macrophages-after-exposure-to-single-dose-irradiation
#18
Wei-Hsiang Kung, Ching-Fang Yu, Andy Chi-Lung Lee, Chi-Dung Yang, Yu-Chen Liu, Fang-Hsin Chen, Hsien-Da Huang
Radiotherapy (RT) is a common cancer treatment approach that accounts for nearly 50% of patient treatment; however, tumor relapse after radiotherapy is still a major issue. To study the crucial role of tumor-associated macrophages (TAMs) in the regulation of tumor progression post-RT, microarray experiments comparing TAM gene expression profiles between unirradiated and irradiated tumors were conducted to discover possible roles of TAMs in initiation or contribution to tumor recurrence following RT, taking into account the relationships among gene expression, tumor microenvironment, and immunology...
April 30, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28533222/fractionated-radiation-therapy-stimulates-antitumor-immunity-mediated-by-both-resident-and-infiltrating-polyclonal-t-cell-populations-when-combined-with-pd-1-blockade
#19
Simon J Dovedi, Eleanor J Cheadle, Amy L Popple, Edmund Poon, Michelle Morrow, Ross Stewart, Erik C Yusko, Catherine M Sanders, Marissa Vignali, Ryan O Emerson, Harlan S Robins, Robert W Wilkinson, Jamie Honeychurch, Timothy M Illidge
Purpose: Radiotherapy is a highly effective anticancer treatment forming part of the standard of care for the majority of patients, but local and distal disease recurrence remains a major cause of mortality. Radiotherapy is known to enhance tumor immunogenicity; however, the contribution and mechanisms of radiotherapy-induced immune responses are unknown.Experimental Design: The impact of low-dose fractionated radiotherapy (5 × 2 Gy) alone and in combination with αPD-1 mAb on the tumor microenvironment was evaluated by flow cytometry and next-generation sequencing of the T-cell receptor (TCR) repertoire...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28529513/ionizing-radiation-induced-immune-and-inflammatory-reactions-in-the-brain
#20
REVIEW
Katalin Lumniczky, Tünde Szatmári, Géza Sáfrány
Radiation-induced late brain injury consisting of vascular abnormalities, demyelination, white matter necrosis, and cognitive impairment has been described in patients subjected to cranial radiotherapy for brain tumors. Accumulating evidence suggests that various degrees of cognitive deficit can develop after much lower doses of ionizing radiation, as well. The pathophysiological mechanisms underlying these alterations are not elucidated so far. A permanent deficit in neurogenesis, chronic microvascular alterations, and blood-brain barrier dysfunctionality are considered among the main causative factors...
2017: Frontiers in Immunology
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