Beneficial Effects of Radiation-Induced Autoantibody on Clinical Outcomes after Stereotactic Radiotherapy for Metastatic Breast Cancer

Purpose: Recent observations suggest that irradiation activates host immunologic response, resulting in potential clinical benefits. The aim of this study is to assess whether autoimmunity induced by stereotactic radiotherapy (SRT) has beneficial impacts on the treatment outcomes for metastatic breast cancer patients. Methods and Materials: Plasma serially corrected before, during, and after SRT on a prospective protocol from 28 patients with metastatic breast cancer were analyzed. Western blot experiments were performed to detect antibody formation to tumor antigens extracted from human breast cancer cell lines, and 13 cytokines were also measured by cytokine array. Results: Tumor-specific antibody of IgM or IgG binding was detected in 50 % (14/28) and 57% (16/28) of the patients, respectively, and median time to appearance of IgM and IgG was 9 days (range, 4-15 days) and 24 days (range, 10-111 days) from the start of RT, respectively. The immuno-responsive group had significantly improved overall survival. The 3-year OS rates of the IgM positive (n=14) and negative (n=14) groups were 68.8 % and 22.2 %, respectively (p=0.027). Similarly, the corresponding rates of IgG positive (n=16) and negative (n=12) groups were 65.6 % and 22.2 %, respectively (p=0.33). Furthermore, the immuno-responsive patients typically had elevated levels of granulocyte macrophage colony-stimulating factor, interferongamma, and tumor necrosis factor-alpha. Conclusion: These data suggest that radiation-induced autoimmunity works synergistically with local effects of radiation, with endogenous cytokines acting as immune adjuvants, ultimately translating to improved survival in patients with metastatic breast cancer.