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Irradiation or radiotherapy and immune

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])...
October 17, 2016: European Journal of Cancer
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Luping Zhang, Yanmei Xu, Jie Shen, Feng He, Dan Zhang, Zhengtang Chen, Yuzhong Duan, Jianguo Sun
BACKGROUND: The combination of dendritic cells (DCs) and cytokine-induced killer cells (CIKs) can induce the anti-tumor immune response and radiotherapy may promote the activity. We aimed to explore the feasibility of DCs/CIKs combined with thoracic radiotherapy (TRT) for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). METHOD: In this study, patients with unresectable stage III/IV NSCLC and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 and previously receiving two or more cycles of platinum-based doublet chemotherapy without disease progression received TRT plus DCs/CIKs or TRT alone until disease progression or unacceptable toxicity...
2016: Radiation Oncology
Raya Saba, Nasir Saleem, David Peace
The abscopal effect is a term that has been used to describe the phenomenon of tumour regression in sites distant from targeted fields of irradiation. It has been reported in multiple malignancies and is thought to be due to a systemic immune response that radiation elicits in the treated individual. We describe the case of a female patient who originally presented with advanced multiple myeloma in 1996 at the age of 50. She failed multiple chemotherapeutic regimens including high-dose melphalan with autologous stem cell transplantation...
2016: BMJ Case Reports
Anna Malecka, Qunwei Wang, Sabaria Shah, Ruhcha V Sutavani, Ian Spendlove, Judith M Ramage, Julie Greensmith, Hester A Franks, Michael J Gough, Anja Saalbach, Poulam M Patel, Andrew M Jackson
Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-α/IL-1β from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro...
August 2016: Journal of Leukocyte Biology
Mary Helen Barcellos-Hoff, Jian-Hua Mao
Clear mechanistic understanding of the biological processes elicited by radiation that increase cancer risk can be used to inform prediction of health consequences of medical uses, such as radiotherapy, or occupational exposures, such as those of astronauts during deep space travel. Here, we review the current concepts of carcinogenesis as a multicellular process during which transformed cells escape normal tissue controls, including the immune system, and establish a tumor microenvironment. We discuss the contribution of two broad classes of radiation effects that may increase cancer: radiation targeted effects that occur as a result of direct energy deposition, e...
2016: Frontiers in Oncology
Shankar Siva, Tomas Kron, Mathias Bressel, Marion Haas, Tao Mai, Shalini Vinod, Giuseppe Sasso, Wenchang Wong, Hien Le, Thomas Eade, Nicholas Hardcastle, Brent Chesson, Daniel Pham, Morten Høyer, Rebecca Montgomery, David Ball
BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is emerging as a non-invasive method for precision irradiation of lung tumours. However, the ideal dose/fractionation schedule is not yet known. The primary purpose of this study is to assess safety and efficacy profile of single and multi-fraction SABR in the context of pulmonary oligometastases. METHODS/DESIGN: The TROG 13.01/ALTG 13.001 clinical trial is a multicentre unblinded randomised phase II study...
2016: BMC Cancer
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