Using immunotherapy to boost the abscopal effect

Published on Feb 16, 2018in Nature Reviews Cancer53.03
· DOI :10.1038/NRC.2018.6
Wilfred Ngwa19
Estimated H-index: 19
(Brigham and Women's Hospital),
Omoruyi Credit Irabor3
Estimated H-index: 3
(Brigham and Women's Hospital)
+ 3 AuthorsSilvia C. Formenti79
Estimated H-index: 79
(Cornell University)
The abscopal effect, which is the regression of metastatic cancer at distant sites during radiotherapy, is somewhat rare but can be promoted by immunotherapy. This Opinion article describes emerging concepts and limitations of using a combination of radiotherapy and immunotherapy to boost the abscopal effect.
📖 Papers frequently viewed together
1,340 Citations
639 Citations
285 Citations
#1Maria E. Rodriguez-Ruiz (University of Navarra)H-Index: 27
#2Inmaculada Rodriguez (University of Navarra)H-Index: 14
Last. Ignacio Melero (University of Navarra)H-Index: 81
view all 8 authors...
Abstract Purpose/Objectives Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory monoclonal antibodies (mAb) to act both on irradiated tumor lesions and on tumors at distant, nonirradiated sites. We have recently reported that external beam radiotherapy achieves abscopal effects when combined with antagonist anti-PD1 mAbs and agonist anti-CD137 (4-1BB) mAbs. The goal of this work is to study the abscopal eff...
16 CitationsSource
#1Claire Vanpouille-Box (Cornell University)H-Index: 23
#2Amandine Alard (NYU: New York University)H-Index: 8
Last. Sandra Demaria (Cornell University)H-Index: 67
view all 10 authors...
Trex1 is an exonuclease that degrades cytosolic DNA and has been associated with modulation of interferon responses in autoimmunity and viral infections. Here, the authors show that Trex1 attenuates the immunogenicity of cancer cells treated with high radiation doses by d…
639 CitationsSource
#1Andrew Bang (U of O: University of Ottawa)H-Index: 8
#2Tyler J. Wilhite (Harvard University)H-Index: 7
Last. Jonathan D. Schoenfeld (Brigham and Women's Hospital)H-Index: 26
view all 12 authors...
Purpose To analyze immune-related adverse events (ir-AEs) in patients treated with radiation and immune checkpoint blockade. Methods and Materials We retrospectively reviewed records from patients with metastatic non-small cell lung cancer, melanoma, or renal cell cancer who received at least 1 cycle of a CTLA-4 or PD-1 inhibitor and radiation. Immune-related adverse events, defined using Common Terminology Criteria for Adverse Events version 4.0, were tabulated in relation to treatment variable...
87 CitationsSource
#1Lorenzo Galluzzi (Paris V: Paris Descartes University)H-Index: 127
#2Aitziber Buqué (UPMC: Pierre-and-Marie-Curie University)H-Index: 23
Last. Guido Kroemer (UPMC: Pierre-and-Marie-Curie University)H-Index: 254
view all 5 authors...
11 CitationsSource
#1Zishuo I. Hu (Mount Sinai Health System)H-Index: 5
#2Heather L. McArthur (Cedars-Sinai Medical Center)H-Index: 25
Last. Alice Y. Ho (Cedars-Sinai Medical Center)H-Index: 29
view all 3 authors...
The abscopal effect refers to the ability of localized radiation to trigger systemic antitumor effects. Over the past 50 years, reports on the abscopal effect arising from conventional radiation have been relatively rare. However, with the continued development and use of immunotherapy strategies incorporating radiotherapy with targeted immunomodulators and immune checkpoint blockade, the abscopal effect is becoming increasingly relevant in less immunogenic tumors such as breast cancer. Here, we...
83 CitationsSource
#1Wilfred Ngwa (University of Massachusetts Lowell)H-Index: 19
#2Francis Boateng (Brigham and Women's Hospital)H-Index: 2
Last. Juergen Hesser (Heidelberg University)H-Index: 10
view all 12 authors...
Radiation therapy (RT) is a crucial component of cancer care, used in the treatment of over 50% of cancer patients. Patients undergoing image guided RT or brachytherapy routinely have inert RT biomaterials implanted into their tumors. The single function of these RT biomaterials is to ensure geometric accuracy during treatment. Recent studies have proposed that the inert biomaterials could be upgraded to “smart” RT biomaterials, designed to do more than 1 function. Such smart biomaterials includ...
22 CitationsSource
#1Raffaella MarconiH-Index: 6
#2S. StrolinH-Index: 5
Last. Lidia StrigariH-Index: 32
view all 4 authors...
Background Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing th...
60 CitationsSource
#1Lorenzo GalluzziH-Index: 127
#2Aitziber BuquéH-Index: 23
Last. Guido KroemerH-Index: 254
view all 5 authors...
Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process?
960 CitationsSource
#1Daniel A. LowH-Index: 69
Magnetic Resonance Imaging (MRI) has been a part of radiation therapy for many years, but its role is expanding. MR provides soft tissue contrast that is superior to what can be obtained with computed tomography (CT), the modality used most often to support radiation therapy treatment simulation. There are a number of critical challenges to employing MR for simulation imaging, namely the reduced spatial fidelity, and the lack of a direct relationship between MR image values and electron density,...
3 CitationsSource
#1Jinjun Shi (Brigham and Women's Hospital)H-Index: 44
#2Philip W. Kantoff (MSK: Memorial Sloan Kettering Cancer Center)H-Index: 134
Last. Omid C. Farokhzad (KAU: King Abdulaziz University)H-Index: 104
view all 4 authors...
This Review summarizes progress in applying nanotechnology to cancer treatment and discusses the challenges of clinical translation and opportunities to develop more effective nanotherapeutics through our increasing understanding of tumour biology and nano–bio interactions.
2,091 CitationsSource
Cited By365
#1Ting Fan (HUST: Huazhong University of Science and Technology)H-Index: 5
#2Wenping Ye (HUST: Huazhong University of Science and Technology)
Last. Jun Luo (HUST: Huazhong University of Science and Technology)H-Index: 2
view all 14 authors...
Abstract null null Chemo-immunotherapy has the superiority of remedying malignant and metastatic tumors, and acquiring better therapeutic effect as well as prognosis than monotherapy. Herein, we report a kind of pH-responsive core-shell nanoparticles to achieve the co-delivery of oxaliplatin intermediate (oxa im) (HCLO NPs) and cytosine-guanine containing oligodeoxynucleotides (CpG) for cancer treatment. The nanoparticles comprise the core of lipid-coated calcium carbonate and the outer layer of...
#1Yuting Cao (Tianjin Medical University)H-Index: 1
#2Yan ZhouH-Index: 3
Last. Shao-Kai Sun (Tianjin Medical University)
view all 7 authors...
Abstract The minimal invasive percutaneous microwave ablation (MWA) combined with immunotherapy is a promising technique in clinic for the treatment of primary and metastatic tumors. However, elaborate encapsulation carrier designs, complex cellular engineering, and poor applicability are the vexing problems difficult to solve currently. Herein, a general strategy was proposed for the design of an injectable microwave-sensitive immune hydrogel for combined MWA and immunotherapy in vivo for the f...
#1Qiuyan Guo (Ha Tai: Xiamen University)H-Index: 1
#2C.P. Wang (Ha Tai: Xiamen University)H-Index: 8
Last. Lei Ren (Ha Tai: Xiamen University)H-Index: 32
view all 9 authors...
Abstract null null Tumor vaccines have made a significant breakthrough in clinical trials of cancer therapy, but have shown limited efficacy. Herein, we develop a novel tumor vaccine delivery strategy through a biodegradable microneedle patch (MN), which allows sustained release of tumor antigen and induces long term anti-tumor response. A tumor antigen peptide (OVA257–264: SIINFEKL) was fused with hepatitis B core (HBc) protein virus like particles (OVA-HBc VLPs) to increase the immunogenicity ...
#1Joshua J. Li (CUHK: The Chinese University of Hong Kong)H-Index: 1
#2Julia Y. Tsang (CUHK: The Chinese University of Hong Kong)H-Index: 5
Last. Gary Tse (CUHK: The Chinese University of Hong Kong)H-Index: 50
view all 0 authors...
The tumor microenvironment (TME) in breast cancer comprises local factors, cancer cells, immune cells and stromal cells of the local and distant tissues. The interaction between cancer cells and their microenvironment plays important roles in tumor proliferation, propagation and response to therapies. There is increasing research in exploring and manipulating the non-cancerous components of the TME for breast cancer treatment. As the TME is now increasingly recognized as a treatment target, its ...
#1Justyna Błach (Medical University of Lublin)H-Index: 1
#2Kamila Wojas-Krawczyk (Medical University of Lublin)H-Index: 10
Last. Paweł Krawczyk (Medical University of Lublin)H-Index: 17
view all 0 authors...
Immune checkpoint inhibitors (ICIs) have a huge impact on clinical treatment results in non-small cell lung cancer (NSCLC). Blocking antibodies targeting programmed cell death protein 1 (PD-1), programmed cell death protein ligand 1 (PD-L1) or CTLA-4 (cytotoxic T cell antigen 4) have been developed and approved for the treatment of NSCLC patients. However, a large number of patients develop resistance to this type of treatment. Primary and secondary immunotherapy resistance are distinguished. No...
#1Elliot Akama-Garren (Brigham and Women's Hospital)H-Index: 1
#2Zachary S. Morris (UW: University of Wisconsin-Madison)H-Index: 17
Last. Jonathan D. Schoenfeld (Brigham and Women's Hospital)H-Index: 26
view all 5 authors...
Immune checkpoint inhibitors (ICIs) lead to durable responses in a subset of cancer patients, but most patients do not respond to ICI, prompting interest in combining immunotherapy with other therapeutic regimens. Preclinical evidence supports the potential for therapeutic synergy between immunotherapy and radiotherapy through modulation of the tumor microenvironment and anti-tumor immune responses. Local therapy also has the potential to overcome localized sites of relative immune suppression a...
#1Kara Magee (UW: University of Wisconsin-Madison)
#2Ian Marsh (UW: University of Wisconsin-Madison)H-Index: 6
Last. Christine JaskowiakH-Index: 3
view all 18 authors...
RATIONALE Murine syngeneic tumor models have revealed efficacious systemic antitumor responses following primary tumor in situ vaccination combined with targeted radionuclide therapy to secondary or metastatic tumors. Here we present studies on the safety and feasibility of this approach in a relevant translational companion dog model (n = 17 dogs) with advanced cancer. METHODS The three component of the combination immuno-radiotherapy approach were employed either separately or in combination i...
#1Melgious Jin Yan Ang (NUS: National University of Singapore)H-Index: 3
#2Siew Yin Chan (Agency for Science, Technology and Research)H-Index: 7
Last. Xiaogang Liu (NUS: National University of Singapore)H-Index: 102
view all 6 authors...
Cancer involves a collection of diseases with a common trait - dysregulation in cell proliferation. At present, traditional therapeutic strategies against cancer have limitations in tackling various tumors in clinical settings. These include chemotherapeutic resistance and the inability to overcome intrinsic physiological barriers to drug delivery. Nanomaterials have presented promising strategies for tumor treatment in recent years. Nanotheranostics combine therapeutic and bioimaging functional...
#1Alex De Caluwe (ULB: Université libre de Bruxelles)H-Index: 4
#2Laurence Buisseret (ULB: Université libre de Bruxelles)H-Index: 17
Last. Drisis Stylianos (ULB: Université libre de Bruxelles)
view all 17 authors...
BACKGROUND Residual breast cancer after neo-adjuvant chemotherapy (NACT) predicts disease outcome and is a surrogate for survival in aggressive breast cancer (BC) subtypes. Pathological complete response (pCR) rate, however, is lower for luminal B BC in comparison to the triple negative (TNBC) and HER2+ subtypes. The addition of immune checkpoint blockade (ICB) to NACT has the potential to increase pCR rate but is hampered by the lower immunogenicity of luminal B BC. Novel strategies are needed ...
#1Seung Woo Chung (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 3
#2Yunxuan Xie (JHUSOM: Johns Hopkins University School of Medicine)
Last. Jung Soo Suk (JHUSOM: Johns Hopkins University School of Medicine)H-Index: 34
view all 3 authors...
Immunotherapy has emerged as an unprecedented hope for the treatment of notoriously refractory cancers. Numerous investigational drugs and immunotherapy-including combination regimens are under preclinical and clinical investigation. However, only a small patient subpopulation across different types of cancer responds to the therapy due to the presence of several mechanisms of resistance. There have been extensive efforts to overcome this limitation and to expand the patient population that coul...