Priming and Propagating Anti-tumor Immunity: Focal Hypofractionated Radiation for in Situ Vaccination and Systemic Targeted Radionuclide Theranostics for Immunomodulation of Tumor Microenvironments
Year: 2020
Type: review
Abstract: Recent preclinical and clinical studies have elucidated mechanisms whereby radiation therapy influences the anti-tumor immune response. Immunogenic cell death and phenotypic changes in tumor cells surviving radiation may underlie this effect and contribute to the capacity of radiation to elicit an in situ tumor vaccine effect. In situ vaccination is a therapeutic strategy that seeks to convert a patient's own tumor into a source of enhanced antigen recognition for the purpose of augmenting a systemic anti-tumor immune response. Capitalizing on the in situ vaccine effect of radiation, several groups have demonstrated anti-tumor efficacy in preclinical models by combining radiation with immune checkpoint blockade. Local delivery of immune adjuvants and/or immune stimulatory cytokines via direct injection into the radiated tumor microenvironment may further increase the in situ vaccine capacity of radiation therapy. However, recent studies suggest that in some contexts this effect is antagonized by the presence of distant untreated sites of disease that may dampen the systemic immune response generated by in situ vaccination through a phenomenon termed concomitant immune tolerance. Concomitant immune tolerance may be overcome by delivering radiation to all sites of metastatic disease, however this is often not possible to safely achieve using external beam radiation therapy without considerable risk of lymphopenia that would negate the immune effects of in situ vaccination. For patients with widespread metastatic disease, alternative strategies may include systemic treatment with targeted radionuclide therapies alone or in combination with an external beam radiation therapy-based in situ vaccine approach.
Source: Seminars in Radiation Oncology
Authors: Justin C. Jagodinsky, Zachary S. Morris
Institution: University of Wisconsin–Madison
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,820
Awards: Head and Neck Cancer SPORE at the University of Wisconsin, Immunomodulation of the Tumor Microenvironment with Molecular Targeted Radiotherapy to Facilitate an Adaptive Anti-Tumor Immune Response to Combined Modality Immunotherapies, Combining Radiation and Tumor-specific AntIbody Therapies to Elicit in Situ Tumor Vaccination, Integrated Training For Physician-Scientists, UW Comprehensive Cancer Center Support, NRSA Training Core
OpenAlex ID: W3021868409