Abstract The combination of radiation therapy and immune checkpoint inhibitors has raised interest as possibly having synergistic antitumor effects. Radiation can induce both a local response as well as a systemic one that stimulates immune cells, which then can be further potentiated by immunotherapy. This abscopal effect has been validated in preclinical studies and is currently being studied in clinical trials, though it has yet to be reported in gynecologic cancers. A 64-year-old woman initially presented with vaginal bleeding and was subsequently diagnosed with stage IIIC endometrial adenocarcinoma with pelvic and para-aortic lymphadenopathy. She underwent surgical resection with adjuvant carboplatin and paclitaxel. Follow-up CT scans showed progression of disease, and over the next 18 months, the patient was sequentially treated with doxorubicin, topotecan, melphalan, docetaxel, and capecitabine. Analysis of a tumor biopsy demonstrated an MMR deficient phenotype with absent MLH1 and PMS2. Based on the recently-published data on the efficacy of PD-1 inhibitors in MMR deficient solid tumors, the patient was started on nivolumab. Meanwhile, she was given palliative radiation therapy to the following areas: painful cutaneous metastases on her left thigh; an L3 spinal metastasis; lymph nodes in the retroperitoneum, external iliacs, and left inguinal chain; and a symptomatic bladder mass. After radiation, the patient exhibited a strong partial response not only in the targeted lesions but also throughout her tumor burden, consistent with an abscopal effect. This response was sustained over many months and repeatable with each radiation session. The synergistic use of radiation therapy and immune checkpoint blockade may thus represent a powerful treatment modality in endometrial cancer and warrants further clinical investigation. Citation Format: Michael S. Oh, Young Chae. Repeated abscopal effect with radiation and anti-PD-1 blockade in MMR deficient endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3629.