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Radiation immune cancer

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https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#1
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29780392/tumor-derived-apoptotic-vesicles-with-death-they-do-part
#2
REVIEW
Morad-Remy Muhsin-Sharafaldine, Alexander D McLellan
Tumor cells release lipid particles known as extracellular vesicles (EV) that contribute to cancer metastasis, to the immune response, and to thrombosis. When tumors are exposed to radiation or chemotherapy, apoptotic vesicles (ApoVs) are released in abundance as the plasma membrane delaminates from the cytoskeleton. Recent studies have suggested that ApoVs are distinct from the EVs released from living cells, such as exosomes or microvesicles. Depending on their treatment conditions, tumor-released ApoV have been suggested to either enhance or suppress anti-cancer immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29774312/breast-cancer-prevention-current-approaches-and-future-directions
#3
REVIEW
Edward R Sauter
The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease...
April 2018: European journal of breast health
https://www.readbyqxmd.com/read/29774202/loss-of-the-cyclin-dependent-kinase-inhibitor-1-in-the-context-of-brachyury-mediated-phenotypic-plasticity-drives-tumor-resistance-to-immune-attack
#4
Duane H Hamilton, Kristen K McCampbell, Claudia Palena
The acquisition of mesenchymal features by carcinoma cells is now recognized as a driver of metastasis and tumor resistance to a range of anticancer therapeutics, including chemotherapy, radiation, and certain small-molecule targeted therapies. With the recent successful implementation of immunotherapies for the treatment of various types of cancer, there is growing interest in understanding whether an immunological approach could be effective at eradicating carcinoma cells bearing mesenchymal features. Recent studies, however, demonstrated that carcinoma cells that have acquired mesenchymal features may also exhibit decreased susceptibility to lysis mediated by immune effector cells, including antigen-specific CD8+ T cells, innate natural killer (NK), and lymphokine-activated killer (LAK) cells...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29769148/current-landscape-and-future-of-dual-anti-ctla4-and-pd-1-pd-l1-blockade-immunotherapy-in-cancer-lessons-learned-from-clinical-trials-with-melanoma-and-non-small-cell-lung-cancer-nsclc
#5
REVIEW
Young Kwang Chae, Ayush Arya, Wade Iams, Marcelo R Cruz, Sunandana Chandra, Jaehyuk Choi, Francis Giles
Immunotherapy is among the most rapidly evolving treatment strategies in oncology. The therapeutic potential of immune-checkpoint inhibitors is exemplified by the recent hail of Food and Drug Administration (FDA) approvals for their use in various malignancies. Continued efforts to enhance outcomes with immunotherapy agents have led to the formulation of advanced treatment strategies. Recent evidence from pre-clinical studies evaluating immune-checkpoint inhibitors in various cancer cell-lines has suggested that combinatorial approaches may have superior survival outcomes compared to single-agent immunotherapy regimens...
May 16, 2018: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29761935/the-application-of-transcriptional-benchmark-dose-modeling-for-deriving-thresholds-of-effects-associated-with-solar-simulated-ultraviolet-radiation-exposure
#6
Sami S Qutob, Vinita Chauhan, Byron Kuo, Andrew Williams, Carole L Yauk, James P McNamee, B Gollapudi
Considerable data has been generated to elucidate the transcriptional response of cells to ultraviolet radiation (UVR) exposure providing a mechanistic understanding of UVR-induced cellular responses. However, using these data to support standards development has been challenging. In this study, we apply benchmark dose (BMD) modeling of transcriptional data to derive thresholds of gene responsiveness following exposure to solar-simulated UVR. Human epidermal keratinocytes were exposed to three doses (10, 20, 150 kJ/m2 ) of solar simulated UVR and assessed for gene expression changes 6 and 24 hr postexposure...
May 15, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29760710/ionizing-radiation-induces-morphological-changes-and-immunological-modulation-of-jurkat-cells
#7
Patrick Voos, Sebastian Fuck, Fabian Weipert, Laura Babel, Dominique Tandl, Tobias Meckel, Stephanie Hehlgans, Claudia Fournier, Anna Moroni, Franz Rödel, Gerhard Thiel
Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL) to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29752716/low-dose-irradiated-mesenchymal-stromal-cells-break-tumor-defensive-properties-in-vivo
#8
Francesca Romana Stefani, Sofia Eberstål, Stefano Vergani, Trine A Kristiansen, Johan Bengzon
Solid tumors, including gliomas, still represent a challenge to clinicians and first line treatments often fail, calling for new paradigms in cancer therapy. Novel strategies to overcome tumor resistance are mainly represented by multi-targeted approaches, and cell vector-based therapy is one of the most promising treatment modalities under development. Here, we show that mouse bone marrow-derived mesenchymal stromal cells (MSCs), when primed with low-dose irradiation (irMSCs), undergo changes in their immunogenic and angiogenic capacity and acquire anti-tumoral properties in a mouse model of glioblastoma (GBM)...
May 11, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29748391/tumor-specific-inhibition-of-in-situ-vaccination-by-distant-untreated-tumor-sites
#9
Zachary S Morris, Emily I Guy, Lauryn R Werner, Peter M Carlson, Clinton M Heinze, Jasdeep S Kler, Sara M Busche, Abigail A Jaquish, Raghava N Sriramaneni, Lakeesha Carmichael, Hans Loibner, Stephen D Gillies, Alan J Korman, Amy K Erbe, Jacquelyn A Hank, Alexander L Rakhmilevich, Paul M Harari, Paul M Sondel
In situ vaccination is an emerging cancer treatment strategy that uses local therapies to stimulate a systemic antitumor immune response. We previously reported an in situ vaccination effect when combining radiation (RT) with intra-tumor (IT) injection of tumor-specific immunocytokine (IC), a fusion of tumor-specific antibody and IL2 cytokine. In mice bearing two tumors, we initially hypothesized that delivering RT plus IT-IC to the "primary" tumor would induce a systemic antitumor response causing regression of the "secondary" tumor...
May 10, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29737213/pachymic-acid-sensitizes-gastric-cancer-cells-to-radiation-therapy-by-upregulating-bax-through-hypoxia
#10
Chunwei Lu, Dingfang Cai, Jun Ma
We have previously shown that pachymic acid (PA) inhibited tumorigenesis of gastric cancer (GC) cells. However, the exact mechanism underlying the radiation response of GC was still elusive. To evaluate the effects of PA treatment on radiation response of GC cell lines both in vitro and in vivo, a colony formation assay and xenograft mouse model were employed. Changes in Bax and HIF1[Formula: see text] expressions were assessed in GC cells following PA treatment. Luciferase reporter and chromatin immune-precipitation assays were carried out to investigate the regulation of Bax through HIF1[Formula: see text]...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29732445/radiation-therapy-combined-with-cowpea-mosaic-virus-nanoparticle-in-situ-vaccination-initiates-immune-mediated-tumor-regression
#11
Ravi Patel, Anna E Czapar, Steven Fiering, Nancy L Oleinick, Nicole F Steinmetz
Epithelial ovarian cancer is a deadly gynecologic malignancy because of its late detection, usually after local and distant metastatic spread. These cancers develop resistance to traditional chemotherapeutic agents; therefore, the development of next-generation immunotherapeutic approaches may have a significant promise in improving outcomes. A novel immunotherapeutic approach utilizing combination radiation therapy (RT) with immunostimulatory cowpea mosaic virus (CPMV) was tested in a preclinical syngeneic mouse model of ovarian carcinoma...
April 30, 2018: ACS Omega
https://www.readbyqxmd.com/read/29729210/enhanced-car-t-cell-therapy-a-novel-approach-for-head-and-neck-cancers
#12
Songlin Wang, Zhao Zhu
Head and neck cancer that presents in locally advanced stages often results in a bad prognosis with an increased recurrence rate even after curative resections. Radiation therapy is then applied, with multiple side effects, as adjuvant regional therapy. Because of the high rate of recurrence and mortality, new therapies are needed for patients suffering from head and neck malignant tumors.CAR (chimeric antigen receptor) T cell therapy, which was first devised about 25 years ago, causes the killing or apoptosis of target tumor cells through inducing the secretion of cytokines and granzymes by T cells (Cheadle et al...
May 5, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29723407/rationale-and-emerging-strategies-for-immune-checkpoint-blockade-in-soft-tissue-sarcoma
#13
REVIEW
Amy J Wisdom, Yvonne M Mowery, Richard F Riedel, David G Kirsch
Soft tissue sarcomas (STS) are heterogeneous, mesenchymal malignancies with variable biologic behavior. The primary management for localized STS is surgical resection, which may be combined with neoadjuvant or adjuvant radiation therapy to increase the probability of achieving local control. Many patients with large, high-grade STS develop metastatic disease. Several clinical trials of immune checkpoint blockade for STS have produced promising responses in patients with metastatic disease. In this review, recent and ongoing clinical trials of immune checkpoint inhibition for STS are discussed...
May 3, 2018: Cancer
https://www.readbyqxmd.com/read/29721377/oncolytic-influenza-virus-infection-restores-immunocompetence-of-lung-tumor-associated-alveolar-macrophages
#14
Dörthe Masemann, Katharina Köther, Meike Kuhlencord, Georg Varga, Johannes Roth, Brian Dennis Lichty, Ulf Rüdiger Rapp, Viktor Wixler, Stephan Ludwig
Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and demonstrates high resistance to radiation and chemotherapy. These tumors evade immune system detection by promoting an immunosuppressive tumor microenvironment. Genetic analysis has revealed oncogenic activation of the Ras/Raf/MEK/ERK signaling pathway to be a hallmark of NSCLCs, which promotes influenza A virus (IAV) infection and replication in these cells. Thus, we aimed to unravel the oncolytic properties of IAV infection against NSCLCs in an immunocompetent model in vivo ...
2018: Oncoimmunology
https://www.readbyqxmd.com/read/29721184/correlation-between-lower-balance-of-th2-helper-t-cells-and-expression-of-pd-l1-pd-1-axis-genes-enables-prognostic-prediction-in-patients-with-glioblastoma
#15
Yasuo Takashima, Atsushi Kawaguchi, Tomohiko Kanayama, Azusa Hayano, Ryuya Yamanaka
Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 ( PD-L1 ), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 ( PD-1 ), PDCD1LG2 ( PD-L2 ), and TBX21 ( T-bet ) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29719632/molecular-mechanism-of-bystander-effects-and-related-abscopal-cohort-effects-in-cancer-therapy
#16
REVIEW
Rong Wang, Tingyang Zhou, Wei Liu, Li Zuo
Cancer cells subjected to ionizing radiation may release signals which can influence nearby non-irradiated cells, termed bystander effects. The transmission of bystander effects among cancer cells involves the activation of inflammatory cytokines, death ligands, and reactive oxygen/nitrogen species. In addition to bystander effects, two other forms of non-target effects (NTEs) have been identified in radiotherapy, as one is called cohort effects and the other is called abscopal effects. Cohort effects represent the phenomenon where irradiated cells can produce signals that reduce the survival of neighboring cells within an irradiated volume...
April 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29709495/morphological-changes-induced-by-intraprostatic-psa-based-vaccine-in-prostate-cancer-biopsies-phase-i-clinical-trial
#17
Maria J Merino, A Peter, Vanessa Moreno, Sara Gil, Jeffrey Schlom, James L Gulley
Immunotherapy is a novel treatment for many tumors including prostate cancer. Little is known about the histological changes in prostate biopsies caused by the prostatic-specific antigen (PSA)-based vaccine. This study evaluated the histopathological effects in prostate biopsies of recombinant fowlpox (rF) virus-based vaccine engineered to present the PSA and three costimulatory molecules (collectively labeled as PSA-TRICOM). This vaccine has shown that it can break tolerance of the PSA, and its administration directly into a tumor enables the affected tumor cells to act as antigen-presenting cells activating new T-cells, and broadening the immune response to recognize and kill tumor...
April 27, 2018: Human Pathology
https://www.readbyqxmd.com/read/29698131/exposure-of-the-bone-marrow-microenvironment-to-simulated-solar-and-galactic-cosmic-radiation-induces-biological-bystander-effects-on-human-hematopoiesis
#18
Graça Almeida-Porada, Christopher Rodman, Bradford Kuhlman, Egil Brudvik, John Moon, Sunil George, Peter Guida, Satria P Sajuthi, Carl D Langefeld, Stephen J Walker, Paul F Wilson, Christopher D Porada
The stem cell compartment of the hematopoietic system constitutes one of the most radiosensitive tissues of the body and leukemias represent one of the most frequent radiogenic cancers with short latency periods. As such, leukemias may pose a particular threat to astronauts during prolonged space missions. Control of hematopoiesis is tightly governed by a specialized bone marrow (BM) microenvironment/niche. As such, any environmental insult that damages cells of this niche would be expected to produce pronounced effects on the types and functionality of hematopoietic/immune cells generated...
April 26, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29694234/expanding-the-therapeutic-index-of-radiation-therapy-by-normal-tissue-protection
#19
Pierre Montay-Gruel, Lydia Meziani, Chakradhar Yakkala, Marie-Catherine Vozenin
Normal tissue damages induced by radiation therapy remain dose-limiting factors in Radiation Oncology and this is still true despite recent advances in treatment planning and delivery of image-guided radiation therapy. Additionally, as the number of long-term cancer survivors increases, unacceptable complications emerge and dramatically reduce the patients' quality of life. This means that patients and clinicians expect discovery of new options for the therapeutic management of radiation-induced complications...
April 25, 2018: British Journal of Radiology
https://www.readbyqxmd.com/read/29691296/tryptophan-metabolism-contributes-to-radiation-induced-immune-checkpoint-reactivation-in-glioblastoma
#20
Pravin Kesarwani, Antony Prabhu, Shiva Kant, Praveen Kumar, Stewart F Graham, Katie L Buelow, George D Wilson, Christopher Ryan Miller, Prakash Chinnaiyan
PURPOSE: Immune checkpoint inhibitors designed to revert tumor-induced immune suppression have emerged as potent anti-cancer therapies. Tryptophan metabolism represents an immune checkpoint and targeting this pathway's rate limiting enzyme IDO1 is actively being investigated clinically. Here, we studied the intermediary metabolism of tryptophan metabolism in glioblastoma and evaluated the activity of the IDO1 inhibitor GDC-0919, both alone and in combination with radiation (RT).  Experimental Design: LC/GC-MS and expression profiling was performed for metabolomic and genomic analyses of patient-derived glioma...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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