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Purpose/objectivesPreclinical 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 effects of radiotherapy instigated by brachytherapy techniques.Methods and materialsMice bearing a subcutaneous colorectal carcinoma, MC38 (colorectal cancer), in both flanks were randomly assigned to receive brachytherapy or not (8 Gy × three fractions) to only one of the two grafted tumors, in combination with intraperitoneal immunostimulatory monoclonal antibodies (anti-PD1, anti-CD137, and/or their respective isotype controls). To study the abscopal effects of brachytherapy, we established an experimental set up that permits irradiation of mouse tumors sparing a distant site resembling metastasis. Such second nonirradiated tumor was used as indicator of abscopal effect. Tumor size was monitored every 2 days.ResultsAbscopal effects on distant nonirradiated subcutaneous tumor lesions of transplanted MC38-derived tumors only took place when brachytherapy was combined with immunostimulatory anti-PD1 and/or anti-CD137 mAbs.ConclusionsOur results demonstrate that immunotherapy-potentiated abscopal effects can be attained by brachytherapy. Accordingly, immunotherapy plus brachytherapy combinations are suitable for clinical translation.

Original publication




Journal article



Publication Date





1246 - 1251


Division of Immunology and Immunotherapy, Center for Applied Medical Research (CIMA), University of Navarra and Instituto de Investigacion Sanitaria de Navarra (IdISNA), Pamplona, Spain; Department of Oncology, University Clinic of Navarra, Pamplona, Spain; University Clinic, University of Navarra and Instituto de Investigacion Sanitaria de Navarra (IdISNA), Pamplona, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Spain. Electronic address:


Cell Line, Tumor, Animals, Mice, Inbred C57BL, Humans, Adenocarcinoma, Colorectal Neoplasms, Immunologic Factors, Antibodies, Monoclonal, Brachytherapy, Female, Programmed Cell Death 1 Receptor, Tumor Necrosis Factor Receptor Superfamily, Member 9