The Abscopal Effect of Radiation Therapy

Craig, Daniel J.; Nanavaty, Nisha S.; Devanaboyina, Monika; Stanbery, Laura; Hamouda, Danae; Edelman, Gerald M.; Dworkin, Lance D.; Nemunaitis, John

doi:10.2217/fon-2020-0994

Cited by 77 publications

(64 citation statements)

References 86 publications

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“…Adapted from "Antigen Presentation in Cancer", by BioRender.com (2021). Retrieved from https://app.biorender.com/biorender-templates "Abscopal Effect"-an observation of focal intervention inducing a systemic antitumor response in sites outside the treatment area [29]. This is presumably due to RT-induced tumor cell injury leading production of additional tumor antigens which are then engulfed by APCs [30,31].…”

Section: [Io Barrier] Low Tumor Neoantigen Burdenmentioning

confidence: 99%

Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance

Heumann

Azad

2021

Cancer Metastasis Rev

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To date, the use of immune checkpoint inhibitors has proven largely ineffective in patients with advanced pancreatic ductal adenocarcinoma. A combination of low tumor antigenicity, deficits in immune activation along with an exclusive and suppressive tumor microenvironment result in resistance to host defensives. However, a deepening understanding of these immune escape and suppressive mechanisms has led to the discovery of novel molecular targets and treatment strategies that may hold the key to a long-awaited therapeutic breakthrough. In this review, we describe the tumor-intrinsic and microenvironmental barriers to modern immunotherapy, examine novel immune-based and targeted modalities, summarize relevant pre-clinical findings and human experience, and, finally, discuss novel synergistic approaches to overcome immune-resistance in pancreatic cancer. Beyond checkpoint inhibition, immune agonists and anti-tumor vaccines represent promising strategies to stimulate host response via activation and expansion of anti-tumor immune effectors. Off-the-shelf natural killer cell therapies may offer an effective method for bypassing downregulated tumor antigen presentation. In parallel with this, sophisticated targeting of crosstalk between tumor and tumor-associated immune cells may lead to enhanced immune infiltration and survival of antitumor lymphocytes. A future multimodal treatment strategy involving immune priming/activation, tumor microenvironment reprogramming, and immune checkpoint blockade may help transform pancreatic cancer into an immunogenic tumor.

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Section: [Io Barrier] Low Tumor Neoantigen Burdenmentioning

confidence: 99%

Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance

Heumann

Azad

2021

Cancer Metastasis Rev

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“…It occurs in addition to the local effect of radiation. An antitumor response throughout the body is induced, reaching distant sites, which were not irradiated [105]. The mechanisms for the abscopal effect are not fully understood, but the immunological hypothesis supports that it occurs due to immunogenic responses initiated by RT-induced DNA breaks.…”

Section: Nanocarriers Designed To Boost the Abscopal Effectmentioning

confidence: 99%

Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy

Gomes

Franco²

2022

Pharmaceutics

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Cancer is responsible for a significant proportion of death all over the world. Therefore, strategies to improve its treatment are highly desired. The use of nanocarriers to deliver anticancer treatments has been extensively investigated and improved since the approval of the first liposomal formulation for cancer treatment in 1995. Radiotherapy (RT) is present in the disease management strategy of around 50% of cancer patients. In the present review, we bring the state-of-the-art information on the combination of nanocarrier-assisted delivery of molecules and RT. We start with formulations designed to encapsulate single or multiple molecules that, once delivered to the tumor site, act directly on the cells to improve the effects of RT. Then, we describe formulations designed to modulate the tumor microenvironment by delivering oxygen or to boost the abscopal effect. Finally, we present how RT can be employed to trigger molecule delivery from nanocarriers or to modulate the EPR effect.

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“…Compounds that target these survival pathways or that induce excessive amounts of ER stress are very effective in targeting MM cells, and it is tempting to speculate that ICD is an important mode of action of MM treatment as recently demonstrated for bortezomib [124]. Even radiation therapy might have an abscopal effect [125], which is a phenomenon of tumor regression in sites distant from targeted fields of irradiation and might be explained by the systemic immune response that radiation causes [126].…”

Section: Standard Of Care Treatmentsmentioning

confidence: 99%

Harnessing the Immune System to Fight Multiple Myeloma

Krejcik

Barnkob

Nyvold

et al. 2021

Cancers

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Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects.

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The Abscopal Effect of Radiation Therapy

Cited by 77 publications

References 86 publications

Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance

Next-generation immunotherapy for pancreatic ductal adenocarcinoma: navigating pathways of immune resistance

Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy

Harnessing the Immune System to Fight Multiple Myeloma

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