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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
Jéssica Ribeiro Gomes, Rafael A Schmerling, Carolina K Haddad, Douglas J Racy, Robson Ferrigno, Erlon Gil, Pedro Zanuncio, Antônio C Buzaid
Abscopal effect is a rare phenomenon characterized by tumor regression of untreated metastatic lesions after a local therapy (eg, radiotherapy). We studied the probability of abscopal effect with radiotherapy associated with anti-programmed death cell 1 (PD1) therapy after progression on anti-PD1. This study is a retrospective analysis of patients treated with nivolumab or pembrolizumab for melanoma, non-small cell lung cancer (NSCLC) and renal cancer at Antônio Ermírio de Moraes Oncology Center, Brazil. To be eligible for this analysis, patients must have had unequivocal evidence of disease progression on anti-PD1 therapy and subsequent radiotherapy for any tumor site while still receiving anti-PD1...
November 2016: Journal of Immunotherapy
S M Barton, J S Sims, A Kadenhe-Chiweshe, F S Dela Cruz, A T Turk, C F Mazzeo, A L Kung, D Yamashiro, E P Connolly
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
R F Carvalho, R Ferrigno, R C Marotta, M P F Amarantes, R A Schmerling, C K Haddad, E Gil, P L Moraes, P H Zanuncio, A C Buzaid
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
B Schrand, A P Benaduce, E Gilboa, A S Ishkanian
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
K Nakajima, Y Shibamoto, M Kobayashi, T Takaoka, T Murai, Y Manabe, C Sugie, T Yanagi
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
N H Nicolay, S Schölch, C Rauber, R Lopez Perez, J Debus, P E Huber
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Lorna G Keenan, Siobhra O'Sullivan, Aisling Glynn, Martin Higgins, Aileen Flavin, Sinead Brennan
INTRODUCTION: Adjuvant radiotherapy is proven to prevent lymph node field relapse after therapeutic lymphadenectomy for melanoma, but does not improve overall survival based on current data. There remains a high rate of distant relapse. This study reports patterns of failure in patients treated with adjuvant radiotherapy, looking at factors associated with distant metastasis and comparing this to recent literature. METHODS: This retrospective study included patients treated with adjuvant nodal irradiation after lymphadenectomy between June 2012 and March 2015...
September 25, 2016: Journal of Medical Imaging and Radiation Oncology
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
Tsuguhide Takeshima, Laurentiu M Pop, Aaron Laine, Puneeth Iyengar, Ellen S Vitetta, Raquibul Hannan
Radiation therapy (RT), a major modality for treating localized tumors, can induce tumor regression outside the radiation field through an abscopal effect that is thought to involve the immune system. Our studies were designed to understand the early immunological effects of RT in the tumor microenvironment using several syngeneic mouse tumor models. We observed that RT induced sterile inflammation with a rapid and transient infiltration of CD11b(+)Gr-1(high+) neutrophils into the tumors. RT-recruited tumor-associated neutrophils (RT-Ns) exhibited an increased production of reactive oxygen species and induced apoptosis of tumor cells...
October 4, 2016: Proceedings of the National Academy of Sciences of the United States of America
Elizabeth Marie Krcik
PURPOSE: To analyze current preclinical trials and early clinical trials on the effects of concomitant anti-programmed death ligand 1 (anti-PD-L1) immunotherapy and radiation therapy on progression-free survival (PFS) and overall survival (OS) for advanced melanoma and metastatic non-small cell lung cancer (NSCLC) patients. METHODS: A literature review was conducted to find current articles about radiation and anti-PD-L1 combinatorial therapy to gain knowledge about T-lymphocyte (T-cell) mediated immune responses, preclinical mouse tumor trials, and early clinical trials...
September 2016: Radiologic Technology
Fernanda G Herrera, Jean Bourhis, George Coukos
Approximately one-half of patients with newly diagnosed cancer and many patients with persistent or recurrent tumors receive radiotherapy (RT), with the explicit goal of eliminating tumors through direct killing. The current RT dose and schedule regimens have been empirically developed. Although early clinical studies revealed that RT could provoke important responses not only at the site of treatment but also on remote, nonirradiated tumor deposits-the so-called "abscopal effect"- the underlying mechanisms were poorly understood and were not therapeutically exploited...
August 29, 2016: CA: a Cancer Journal for Clinicians
Richard C Walshaw, Jamie Honeychurch, Tim M Illidge
Radiotherapy (RT) is effective at cytoreducing tumours and until relatively recently the focus in radiobiology has been on the direct effects of RT on the tumour. Increasingly, however, the effect of RT on the tumour vasculature, tumour stroma and immune system are recognized as important to the overall outcome. RT is known to lead to the induction of immunogenic cell death (ICD), which can generate tumour-specific immunity. However, systemic immunity leading to "abscopal effects" resulting in tumour shrinkage outside of the RT treatment field is rare, which is thought to be caused by the immunosuppressive nature of the tumour microenvironment...
October 2016: British Journal of Radiology
Shaveta Mehta, Tim Illidge, Ananya Choudhury
PURPOSE OF REVIEW: Radiotherapy has the potential to augment the host's immune response to cancer. Urological malignancies are highly immunogenic and the combination of radiotherapy and immunotherapy shows promise. In this review, we discuss the effects of radiotherapy on the cancer immune system and highlight the rationale for using the combined approach in prostate, urothelial and renal cancers. Current clinical studies are summarized emphasising the synergistic effects of the combination and the possibility of improved clinical outcomes...
November 2016: Current Opinion in Urology
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
Susan F Slovin
PURPOSE OF REVIEW: The purpose of this review is to identify possible reasons why prostate cancer suboptimally responds to immune therapies. RECENT FINDINGS: Interrogation of the intraprostatic milieu suggests that within the normal prostate, foci of tumor can be surrounded by inflammatory cells that may or may not represent foci of immune sensitivity. Whether or not these cells are specific 'immune responders' depends on a multiplicity of factors within the host and intratumoral/stromal milieu...
November 2016: Current Opinion in Urology
Chunbai He, Xiaopin Duan, Nining Guo, Christina Chan, Christopher Poon, Ralph R Weichselbaum, Wenbin Lin
Advanced colorectal cancer is one of the deadliest cancers, with a 5-year survival rate of only 12% for patients with the metastatic disease. Checkpoint inhibitors, such as the antibodies inhibiting the PD-1/PD-L1 axis, are among the most promising immunotherapies for patients with advanced colon cancer, but their durable response rate remains low. We herein report the use of immunogenic nanoparticles to augment the antitumour efficacy of PD-L1 antibody-mediated cancer immunotherapy. Nanoscale coordination polymer (NCP) core-shell nanoparticles carry oxaliplatin in the core and the photosensitizer pyropheophorbide-lipid conjugate (pyrolipid) in the shell (NCP@pyrolipid) for effective chemotherapy and photodynamic therapy (PDT)...
2016: Nature Communications
Ilinca Popp, Anca Ligia Grosu, Gabriele Niedermann, Dan G Duda
Stereotactic body radiation therapy (SBRT) has become an attractive treatment modality and a safe, non-invasive alternative to surgery to control primary or secondary malignant tumors. While emphasis has been on the local tumor control as a treatment objective for SBRT, the rare but intriguing observations of abscopal (or out-of-field) effects have pointed to the exciting possibility of activating anti-tumor immunity by using high-dose radiation. This review summarizes the available evidence supporting immune modulation by SBRT alone, as well as its potential combination with immunotherapy...
August 2016: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
Vivek Verma, Steven H Lin
Siva and colleagues have demonstrated that localized thoracic radiation resulted in DNA damage at out-of-field sites. Although these interesting findings require validation, we discuss the important clinical implications of these data, especially in the era of immune therapies. Clin Cancer Res; 22(19); 4763-5. ©2016 AACRSee related article by Siva et al., p. 4817.
October 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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
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