Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: A review of cooperative mechanisms and clinical opportunities

In the manuscript, Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: A review of cooperative mechanisms and clinical opportunities by Patel RB et al. (17: 6, pp 995–1003, 2018); the authors cited the wrong references in the following paragraph. The correct citations are now included below: Relatively few preclinical studies have tested the cooperative interaction between brachytherapy and immunotherapies. Indirect neutralization of Tregs with cyclophosphamide- and myeloid-derived suppressor cells with the phosphodiesterase inhibitor sildenafil, respectively, were found to synergize with radium (Ra)-224 loaded wires implanted into weakly immunogenic breast cancer xenografts (4A). This combination, plus administration of the immunoadjuvant, CpG, resulted in the greatest reduction in metastatic tumor volume and number of lung metastases compared with any of the other combinations (5A). The authors concluded that even tumors felt to be weakly immunogenic could be better controlled by combining brachytherapy and immunostimulatory measures. In a subsequent article, Hodge et al. used a CEA + mouse model and CEA-directed vaccine alone or in combination with an iodine-125 (I-125) seed implanted into the primary flank tumor and quantified lung metastases (6A). While neither I-125 alone nor vaccine had any effect on the development of lung metastases, the combined therapy significantly reduced the burden of metastases in the lungs, demonstrating an abscopal effect. 4A.Confino, H., Schmidt, M., Efrati, M., Hochman, I., Umansky, V., Kelson, I., Keisari, Y. Efficient treatment of mouse breast adenocarcinoma by ablation with intratumoral alpha irradiation combined with inhibitors of immunosuppression and CpG. Cancer Immunol Immunother., 65(10), 1149–1158; 2016. e-pub Aug. 6, 2016. https://doi.org/10.1007/s00262-016-1878-6.5A.Confino, H., Hochman, I., Efrati, M., Schmidt, M., Umansky, V., Kelson, I., Keisari, Y. Tumor ablation by intratumoral Ra-224 loaded wires induces anti-tumor immunity against experimental metastatic tumors. Cancer Immunol. Immunother. 64(2):191–199; 2015 [2014 Oct 18 Epub ahead of print]. https://doi.org/10.1007/s00262-014-1626-8.6A.Hodge JW, Sharp HJ, Gameiro SR. Abscopal regression of antigen disparate tumors by antigen cascade after systemic tumor vaccination in combination with local tumor radiation. Cancer Biother Radiopharm. 2012 Feb; 27(1):12–22. https://doi.org/10.1089/cbr.2012.1202. Epub 2012 Jan 27. Combining brachytherapy and immunotherapy to achieve in situ tumor vaccination: A review of cooperative mechanisms and clinical opportunitiesBrachytherapyVol. 17Issue 6PreviewAs immunotherapies continue to emerge as a standard component of treatment for a variety of cancers, the imperative for testing these in combination with other standard cancer therapies grows. Radiation therapy may be a particularly well-suited partner for many immunotherapies. By modulating immune tolerance and functional immunogenicity at a targeted tumor site, radiation therapy may serve as a method of in situ tumor vaccination. In situ tumor vaccination is a therapeutic strategy that seeks to convert a patient's own tumor into a nidus for enhanced presentation of tumor-specific antigens in a way that will stimulate and diversify an antitumor T cell response. Full-Text PDF