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(Irradiation or radiation or radiotherapy) and immune

Kristy Pilbeam, Hongbo Wang, Elizabeth Taras, Rachel J Bergerson, Brianna Ettestad, Todd DeFor, Antonella Borgatti, Daniel A Vallera, Michael R Verneris
Children with high risk sarcoma have a poor prognosis despite surgical resection, irradiation and chemotherapy. Alternative therapies are urgently needed. Urokinase-type plasminogen activator receptor (uPAR) and epidermal growth factor receptor (EGFR) are surface proteins expressed by some pediatric sarcomas. We show for the first time that a de-immunized bispecific ligand toxin, EGFATFKDEL, directed against EGFR and uPAR, successfully targets pediatric sarcoma. Using flow cytometry, we identified a rhabdomyosarcoma (RMS) cell line, RH30, that expresses both uPAR and EGFR, and a Ewing sarcoma (EWS) cell line, TC-71, that expresses only uPAR...
February 23, 2018: Oncotarget
Kimberly M Arnold, Nicole J Flynn, Adam Raben, Lindsay Romak, Yan Yu, Adam P Dicker, Firas Mourtada, Jennifer Sims-Mourtada
In addition to inducing lethal DNA damage in tumor and stromal cells, radiation can alter the interactions of tumor cells with their microenvironment. Recent technological advances in planning and delivery of external beam radiotherapy have allowed delivery of larger doses per fraction (hypofractionation) while minimizing dose to normal tissues with higher precision. The effects of radiation on the tumor microenvironment vary with dose and fractionation schedule. In this review, we summarize the effects of conventional and hypofractionated radiation regimens on the immune system and tumor stroma...
2018: Cancer Growth and Metastasis
Fanny Zulay Acero Brand, Nicolas Suter, Jean-Philippe Adam, Bernard Faulques, Antonio Maietta, Denis Soulières, Normand Blais
BACKGROUND: Pembrolizumab is an anti-programmed death 1 (PD-1) receptor monoclonal antibody that has shown activity as second line treatment for metastatic head and neck squamous cell carcinoma (HNSCC). Immune-related adverse events are now well described complications of PD-1 inhibitors and most organ sites have been shown to be potentially affected. CASE PRESENTATION: We describe a 69-year old patient with a relapsed squamous cell carcinoma of the supraglottic larynx with lung metastasis after receiving adjuvant concurrent cisplatin and radiotherapy...
March 16, 2018: Journal for Immunotherapy of Cancer
Isabella Zhang, Silvia C Formenti, Jonathan P S Knisely
The brain has long been considered an immunologically privileged site, and the role of immunotherapy in treating intracranial disease has only recently been revived-with preclinical evidence showing that the systemic immune system responds to immunotherapy for intracranial disease, and with clinical evidence demonstrating improved locoregional control and survival compared with historical outcomes when immune-directed therapies are combined with radiation. Pharmaceutical industry-supported multi-institutional drug efficacy studies routinely exclude patients with brain metastases, so current evidence for treatment of brain metastases using stereotactic radiosurgery combined with immunotherapy comes from single-institution studies...
March 15, 2018: Oncology (Williston Park, NY)
Anna S Berghoff, Priscilla K Brastianos
Brain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs...
February 2018: Seminars in Neurology
Andrzej T Slominski, Michal A Zmijewski, Przemyslaw M Plonka, Jerzy P Szaflarski, Ralf Paus
The skin, a self-regulating protective barrier organ, is empowered with sensory and computing capabilities to counteract the environmental stressors to maintain/restore disrupted cutaneous homeostasis. These complex functions are coordinated by a cutaneous neuro-endocrine system that also communicates in a bidirectional fashion with the central nervous, endocrine and immune systems, all acting in concert to control body homeostasis. While ultraviolet energy (UV) has played an important role in the origin and evolution of life, UV absorption by the skin not only triggers mechanisms that defend skin integrity and regulate global homeostasis, but also induces skin pathology (e...
March 12, 2018: Endocrinology
Matthew G K Benesch, Iain T K MacIntyre, Todd P W McMullen, David N Brindley
A quarter-century after the discovery of autotaxin in cell culture, the autotaxin-lysophosphatidate (LPA)-lipid phosphate phosphatase axis is now a promising clinical target for treating chronic inflammatory conditions, mitigating fibrosis progression, and improving the efficacy of existing cancer chemotherapies and radiotherapy. Nearly half of the literature on this axis has been published during the last five years. In cancer biology, LPA signaling is increasingly being recognized as a central mediator of the progression of chronic inflammation in the establishment of a tumor microenvironment which promotes cancer growth, immune evasion, metastasis, and treatment resistance...
March 15, 2018: Cancers
Sagus Sampath, Haejung Won, Erminia Massarelli, Min Li, Paul Frankel, Nayana Vora, Lalit Vora, Ellie Maghami, Marcin Kortylewski
Immunomodulation contributes to the antitumor efficacy of the fractionated radiation therapy (RT). Here, we describe immune effects of RT with concurrent systemic cisplatin or cetuximab treatment of patients with stage III-IV head and neck squamous cell carcinoma (HNSCC). Using longitudinally collected blood samples, we identified significant changes in cytokines/chemokines and immune cell populations compared to immune-related gene expression profiles in peripheral blood mononuclear cells (PBMCs). The 7-week combinatorial RT resulted in gradual elevation of proinflammatory mediators (IFNγ, IL-6, TNFɑ, CCL2), while levels of IL-12, cytokine essential for antitumor immune responses, were decreased...
February 16, 2018: Oncotarget
Hironori Yoshino, Miyu Iwabuchi, Yuka Kazama, Maho Furukawa, Ikuo Kashiwakura
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns and induce antiviral immune responses. Recent studies have demonstrated that RLR activation induces antitumor immunity and cytotoxicity against different types of cancer, including lung cancer. However a previous report has demonstrated that ionizing radiation exerts a limited effect on RLR in human monocytic cell-derived macrophages, suggesting that RLR agonists may be used as effective immunostimulants during radiation therapy...
April 2018: Oncology Letters
Jutaek Nam, Sejin Son, Lukasz J Ochyl, Rui Kuai, Anna Schwendeman, James J Moon
Photothermal therapy (PTT) is a promising cancer treatment modality, but PTT generally requires direct access to the source of light irradiation, thus precluding its utility against disseminated, metastatic tumors. Here, we demonstrate that PTT combined with chemotherapy can trigger potent anti-tumor immunity against disseminated tumors. Specifically, we have developed polydopamine-coated spiky gold nanoparticles as a new photothermal agent with extensive photothermal stability and efficiency. Strikingly, a single round of PTT combined with a sub-therapeutic dose of doxorubicin can elicit robust anti-tumor immune responses and eliminate local as well as untreated, distant tumors in >85% of animals bearing CT26 colon carcinoma...
March 14, 2018: Nature Communications
Partha Basu, Ajay Mehta, Minish Jain, Sudeep Gupta, Rajnish V Nagarkar, Subhashini John, Robert Petit
OBJECTIVES: A global unmet medical need exists for effective treatments for persistent, recurrent, or metastatic cervical cancer, as patients have a short life expectancy. Recently, immunotherapies have shown promising survival benefits for patients with advanced forms of cancer. Axalimogene filolisbac (ADXS11-001), a Listeria monocytogenes immunotherapy with a broad effect on the immune system, is under investigation for treatment of human papillomavirus-associated cancers including cervical cancer...
March 14, 2018: International Journal of Gynecological Cancer
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
Mariarosaria Conte, Raffaele De Palma, Lucia Altucci
In recent years, anti-tumor immunotherapy has shown promising results, and immune-oncology is now emerging as the fourth major wave in the treatment of tumors after radiotherapy, chemotherapy and molecular targeted therapy. Understanding the impact of the immune system on neoplastic cells is crucial to improve its effectiveness against cancer. The stratification of patients who might benefit from immunotherapy as well as the personalization of medicine have contributed to the discovery of new immunotherapeutic targets and molecules...
March 10, 2018: International Journal of Biochemistry & Cell Biology
Xuanwei Zhang, Gabriele Niedermann
PURPOSE: Hypofractionated radiation therapy (hRT) combined with immune checkpoint blockade can induce T-cell-mediated local and abscopal antitumor effects. We had previously observed peak levels of tumor-infiltrating lymphocytes (TILs) between days 5 and 8 after hRT. Because TILs are regarded as radiosensitive, hRT schedules extending into this period might be less immunogenic, prompting us to compare clinically relevant, short and extended schedules with equivalent biologically effective doses combined with anti-programmed cell death 1 (PD1) antibody treatment...
February 3, 2018: International Journal of Radiation Oncology, Biology, Physics
Ignacia Braga-Tanaka, Satoshi Tanaka, Atsushi Kohda, Daisaku Takai, Shingo Nakamura, Tetsuya Ono, Kimio Tanaka, Jun-Ichiro Komura
PURPOSE: This review summarizes the results of experiments conducted in the Institute for Environmental Sciences for the past 21 years, focusing on the biological effects of long-term low dose-rate radiation exposure on mice. Mice were chronically exposed to gamma rays at dose-rates of 0.05, 1 or 20 mGy/day for 400 days to total doses of 20, 400 or 8000 mGy, respectively. The dose rates 0.05 mGy/day is comparable to the dose limit for radiation workers. The parameters examined were lifespan, neoplasm incidence, anti-neoplasm immunity, body weight, chromosome aberration(s), gene mutation(s), alterations in mRNA and protein levels, and trans-generational effects...
March 13, 2018: International Journal of Radiation Biology
Tünde Szatmári, Eszter Persa, Enikő Kis, Anett Benedek, Rita Hargitai, Géza Sáfrány, Katalin Lumniczky
PURPOSE: Radiation-induced bystander effects (RIBE) imply the involvement of complex signaling mechanisms, which can be mediated by extracellular vesicles (EVs). Using an in vivo model, we investigated EV-transmitted RIBE in blood plasma and radiation effects on plasma EV miRNA profiles. MATERIALS AND METHODS: C57Bl/6 mice were total-body irradiated with 0.1 and 2Gy, bone marrow-derived EVs were isolated, and injected systemically into naïve, "bystander" animals...
March 13, 2018: International Journal of Radiation Biology
Reginald M Gorczynski, Nuray Erin, Tahir Maqbool, Christopher P Gorczynski, Laura Y Gorczynski
BACKGROUND AND PURPOSE: In BALB/c mice with transplantable breast tumors, we showed that CD200R1KO mice were cured of local and metastatic growth of EMT6 cells following surgical resection of localized tumor and immunization with irradiated cells along with CpG as adjuvant. On the other hand, wild-type (WT) animals treated in the same fashion develop pulmonary and liver metastases within 20 days of surgery. To develop an in vitro system which would mimic the in vivo model and allow exploration of factors controlling tumor invasion as a precursor to in vivo metastasis, we have developed and characterized a two-phase culture system...
March 12, 2018: Breast Cancer: the Journal of the Japanese Breast Cancer Society
Simona Delle Monache, Patrizia Di Fulvio, Ester Iannetti, Luca Valerii, Ludovica Capone, Maria Giovanna Nespoli, Mauro Bologna, Adriano Angelucci
BACKGROUND & AIMS: Vitamin D is a pleiotropic hormone targeting several tissues and is involved in basic homeostatic processes, including bone mineralization, immune response and muscle strength. Although hypovitaminosis D is common in Europe and North America, representing a risk factor for several chronic diseases, the contribution of factors other than sun exposure is largely underestimated. METHODS: In our study, we retrospectively collected data from medical records of women with age between 19 and 80 screened in Central Italy (42°N) for increased risk of metabolic syndrome...
March 2, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Lalit Kumar, P Harish, Prabhat S Malik, S Khurana
Management of cervical cancer has undergone refinement in the past two decades; concurrent chemo-radiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach for patients with locally advanced disease (FIGO stage IIB-IVA). About 30%-40% of such patients fail to achieve complete response; alternative approaches are needed to improve outcome for them. Treatment with bevacizumab (an inhibitor of vascular endothelial growth factor) along with chemotherapy is associated with improved survival in patients with recurrent or metastatic cervical cancer...
February 3, 2018: Current Problems in Cancer
Jeannine S McCune
Immunotherapy is now the fourth pillar of cancer therapy, with surgery, radiation, and traditional chemotherapy being the remaining pillars. Over the past decade, enthusiasm for immunotherapy has increased because of, in part, data showing that it consistently improves overall survival in select patients with historically refractory cancers. This issue covers various aspects of immunotherapy ranging from use of 1) chimeric antigen receptor (CAR) T cells to treat patients with B-cell acute lymphoblastic leukemia; 2) population pharmacokinetic/dynamic modeling to develop new immune checkpoint inhibitors; and 3) simulations of existing population pharmacokinetic models of immunotherapy to minimize waste without compromising exposure and efficacy...
April 2018: Clinical Pharmacology and Therapeutics
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