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Irradiation or radiotherapy and immune

C Yuan, Q Wang
PURPOSE: The aim of this study was to determine whether different radiotherapy (RT) fractionation schemes induce disparate effects on lymphocyte and its subsets in breast cancer patients. METHODS: 60 female patients diagnosed with breast cancer were recruited in this study after receiving modified radical mastectomy and were randomly divided into two groups. One group received irradiation at a standard dose of 50 Gy in 25 fractions and the other at a dose of 40...
March 13, 2018: Clinical & Translational Oncology
Pei Zhang, Xuguang Hu, Bin Liu, Zhe Liu, Cong Liu, Jianming Cai, Fu Gao, Jianguo Cui, Bailong Li, Yanyong Yang
BACKGROUND Carbon ion radiotherapy has been shown to be more effective in cancer radiotherapy than photon irradiation. Influence of carbon ion radiation on cancer microenvironment is very important for the outcomes of radiotherapy. Tumor-infiltrating dendritic cells (DCs) play critical roles in cancer antigen processing and antitumor immunity. However, there is scant literature covering the effects of carbon ion radiation on DCs. In this study, we aimed to uncover the impact of carbon ion irradiation on bone marrow derived DCs...
March 11, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Masoud Najafi, Elahe Motevaseli, Alireza Shirazi, Ghazale Graily, Abolhasan Rezaeyan, Farzad Norouzi, Saeed Rezapoor, Hamid Abdollahi
PURPOSE: Cancer treatment is one of the most challenging diseases in the present era. Among a few modalities for cancer therapy, radiotherapy plays a pivotal role in more than half of all treatments alone or combined with other cancer treatment modalities. Management of normal tissue toxicity induced by radiation is one of the most important limiting factors for an appropriate radiation treatment course. The evaluation of mechanisms of normal tissue toxicity has shown that immune responses especially inflammatory responses play a key role in both early and late side effects of exposure to ionizing radiation (IR)...
March 5, 2018: International Journal of Radiation Biology
Motoo Nomura, Atsushi Otsuka, Michio Yoshimura, Yumi Nonomura, Yo Kaku, Shigemi Matsumoto, Manabu Muto
BACKGROUND: The objective of this study was to evaluate the efficacy and safety of concurrent immune checkpoint inhibitor therapy and radiotherapy (immunoradiotherapy) in patients with metastatic melanoma after progression on nivolumab. PATIENTS AND METHODS: A retrospective review was performed on 16 consecutive patients with metastatic melanoma treated with concurrent immunoradiotherapy after progression on nivolumab. Best responses to immunoradiotherapy were assessed either inside or outside of the radiation fields...
March 3, 2018: Cancer Chemotherapy and Pharmacology
Silvia C Formenti, Percy Lee, Sylvia Adams, Judith D Goldberg, Xiaochun Li, Michael Xie, Josephine Ratikan, Carol Felix, Lin Hwang, Kym Faull, James W Sayre, Sara Hurvitz, John Glaspy, Begoña Comin-Anduix, Sandra Demaria, Dorthe Schaue, William H McBride
PURPOSE: This study examined the feasibility, efficacy (abscopal effect) and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients. EXPERIMENTAL DESIGN: Prospective randomized trial comparing two doses of TGFβ blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metastatic sites whose tumor had progressed after at least one line of therapy were randomized to receive 1 or 10 mg/kg of fresolimumab, every 3 weeks for 5 cycles, with focal radiotherapy to a metastatic site at week 1, (3 doses of 7...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Wilfred Ngwa, Omoruyi Credit Irabor, Jonathan D Schoenfeld, Jürgen Hesser, Sandra Demaria, Silvia C Formenti
More than 60 years ago, the effect whereby radiotherapy at one site may lead to regression of metastatic cancer at distant sites that are not irradiated was described and called the abscopal effect (from 'ab scopus', that is, away from the target). The abscopal effect has been connected to mechanisms involving the immune system. However, the effect is rare because at the time of treatment, established immune-tolerance mechanisms may hamper the development of sufficiently robust abscopal responses. Today, the growing consensus is that combining radiotherapy with immunotherapy provides an opportunity to boost abscopal response rates, extending the use of radiotherapy to treatment of both local and metastatic disease...
February 16, 2018: Nature Reviews. Cancer
Gabriele Babini, Jacopo Morini, Sofia Barbieri, Giorgio Baiocco, Giovanni Battista Ivaldi, Marco Liotta, Paola Tabarelli de Fatis, Andrea Ottolenghi
The protocol adopted in this work aims at unraveling how X-rays perturb the functioning of the intestinal barrier, focusing on the interplay between colorectal tumor cells and the immune system. Colorectal carcinoma is among the most common type of cancer, typically treated by surgery, chemotherapy, and radiotherapy. Advantages of radiotherapy in targeting the tumor are well known. However, even limited exposures of healthy tissues are of great concern, particularly regarding the effects on the intestinal barrier and the immune system...
January 30, 2018: Journal of Visualized Experiments: JoVE
Jeremy Michael Brownstein, Amy Jordan Wisdom, Katherine D Castle, Yvonne M Mowery, Peter M Guida, Chang-Lung Lee, Francesco Tommasino, Chiara La Tessa, Emanuele Scifoni, Junheng Gao, Lixia Luo, Lorraine Da Silva Campos, Yan Ma, Nerissa Williams, Sin-Ho Jung, Marco Durante, David G Kirsch
Carbon ion therapy (CIT) offers several potential advantages for treating cancers compared with X-ray and proton radiotherapy including increased biological efficacy and more conformal dosimetry. However, CIT potency has not been characterized in primary tumor animal models. Here, we calculate the relative biological effectiveness (RBE) of carbon ions compared to X-rays in an autochthonous mouse model of soft tissue sarcoma. We used Cre/loxP technology to generate primary sarcomas in KrasLSL-G12D/+; p53fl/fl mice...
February 7, 2018: Molecular Cancer Therapeutics
Jason J Luke, Jeffrey M Lemons, Theodore G Karrison, Sean P Pitroda, James M Melotek, Yuanyuan Zha, Hania A Al-Hallaq, Ainhoa Arina, Nikolai N Khodarev, Linda Janisch, Paul Chang, Jyoti D Patel, Gini F Fleming, John Moroney, Manish R Sharma, Julia R White, Mark J Ratain, Thomas F Gajewski, Ralph R Weichselbaum, Steven J Chmura
Purpose Stereotactic body radiotherapy (SBRT) may stimulate innate and adaptive immunity to augment immunotherapy response. Multisite SBRT is an emerging paradigm for treating metastatic disease. Anti-PD-1-treatment outcomes may be improved with lower disease burden. In this context, we conducted a phase I study to evaluate the safety of pembrolizumab with multisite SBRT in patients with metastatic solid tumors. Patients and Methods Patients progressing on standard treatment received SBRT to two to four metastases...
February 13, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Hao Feng, Jing-Kun Zhao, Tobias S Schiergens, Pu-Xiongzhi Wang, Bao-Chi Ou, Rami Al-Sayegh, Ming-Lun Li, Ai-Guo Lu, Shuai Yin, Wolfgang E Thasler
BACKGROUND: Radiotherapy remains one of the cornerstones to improve the outcome of colorectal cancer (CRC) patients. Radiotherapy of the CRC not only help to destroy cancer cells but also remodel the tumour microenvironment by enhancing tumour-specific tropism of bone marrow-derived mesenchymal stromal cell (BM-MSC) from the peripheral circulation. However, the role of local MSCs and recruited BM-MSC under radiation were not well defined. Indeed, the functions of BM-MSC without irradiation intervention remained controversial in tumour progression: BM-MSC was previously shown to modulate the immune function of major immune cells, resulting in an impaired immunological sensitivity and to induce an increased risk of tumour recurrence...
February 6, 2018: British Journal of Cancer
Thomas Walle, Rafael Martinez Monge, Adelheid Cerwenka, Daniel Ajona, Ignacio Melero, Fernando Lecanda
Radiotherapy (RT) is currently used in more than 50% of cancer patients during the course of their disease in the curative, adjuvant or palliative setting. RT achieves good local control of tumor growth, conferring DNA damage and impacting tumor vasculature and the immune system. Formerly regarded as a merely immunosuppressive treatment, pre- and clinical observations indicate that the therapeutic effect of RT is partially immune mediated. In some instances, RT synergizes with immunotherapy (IT), through different mechanisms promoting an effective antitumor immune response...
2018: Therapeutic Advances in Medical Oncology
Takanobu Mashiko, Hitomi Takada, Szu-Hsien Wu, Koji Kanayama, Jingwei Feng, Kensuke Tashiro, Rintaro Asahi, Ataru Sunaga, Kazuto Hoshi, Akira Kurisaki, Tsuyoshi Takato, Kotaro Yoshimura
Chronic changes following radiotherapy include alterations in tissue-resident stem cells and vasculatures, which can lead to impaired wound healing. In this study, novel recombinant human collagen peptide (rhCP) scaffolds were evaluated as a biomaterial carrier for cellular regenerative therapy. Human adipose-derived stem cells (hASCs) were successfully cultured on rhCP scaffolds. By hASC culture on rhCP, microarray assay indicated that expression of genes related to cell proliferation and extracellular matrix production was upregulated...
January 26, 2018: Journal of Tissue Engineering and Regenerative Medicine
Arif Ali Chishti, Christa Baumstark-Khan, Kristina Koch, Waldemar Kolanus, Sebastian Feles, Bikash Konda, Abid Azhar, Luis F Spitta, Bernd Henschenmacher, Sebastian Diegeler, Claudia Schmitz, Christine E Hellweg
Nuclear factor kappaB (NF-κB) is a central transcription factor in the immune system and modulates cell survival in response to radiotherapy. Activation of NF-κB was shown to be an early step in the cellular response to ultraviolet A (UVA) and ionizing radiation exposure in human cells. NF-κB activation by the genotoxic stress-dependent sub-pathway after exposure to different radiation qualities had been evaluated to a very limited extent. In addition, the resulting gene expression profile, which shapes the cellular and tissue response, is unknown...
January 25, 2018: Radiation Research
Jean-Pierre Pouget, Alexandros G Georgakilas, Jean-Luc Ravanat
Radiation therapy (from external beams to unsealed and sealed radionuclide sources) takes advantage of the detrimental effects of the clustered production of radicals and reactive oxygen species (ROS). Research has mainly focused on the interaction of radiation with water, which is the major constituent of living beings, and with nuclear DNA, which contains the genetic information. This led to the so-called "target" theory according to which cells have to be hit by ionizing particles to elicit an important biological response, including cell death...
January 19, 2018: Antioxidants & Redox Signaling
Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
BACKGROUND: Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®). METHODS: C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days...
January 16, 2018: Cancer Immunology, Immunotherapy: CII
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
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
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
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
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
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