Abstract 6513: 3,3'-diindolylmethane enhances tumor regression after radiation through protecting normal cells to modulate anti-tumor immunity

Preclinical and clinical data indicate that radiotherapy acts as an immune modifier, having both immunostimulatory and immunosuppressive effects on the tumor immune microenvironment (TIME). 3.39-Diindolylmethane (DIM), the acid-catalyzed dimer of the bioactive indole found in cruciferous vegetables, has long been known for its anticancer properties and has been proposed for use as a cancer prevention agent. The current study characterizes how DIM influences TIME and tumor regression after fractionated radiation treatment using preclinical breast cancer models. We first compared tumor graft models using immune-competent and immune-deficient mouse strains to find out whether immune cells are required for DIM9s effects. Tumor targeted radiation was done using narrow-beam radiation with shielding. Tumor regression was monitored after DIM and radiation combined treatment and radiation alone. Our results indicated that DIM enhanced tumor regression after radiation treatment in immune-competent but not immuno-deficient mice. Data from nCounter® PanCancer immune profiling panel showed DIM increased intratumoral immune cells including cytotoxic T cells, neutrophils and macrophages after radiation and enhanced immunological processes such as adhesion and antigen processing. Expression of several MHC Class II molecules and CD74, a gene encoding chaperone and transport cofactor that assists MHC II molecules folding and presenting, significantly increased in the combined treatment of radiation and DIM. The results showing that DIM treatment alone does not affect tumor growth suggested that DIM9s radioprotective effect on non-tumoral cells, including stromal cells and immune cells, plays a critical role in promoting a microenvironment that favors anti-tumor immunity. Additional experiments showed that DIM protected normal cells from radiation-caused immediate injuries in vitro and in vivo. In summary, DIM9s radioprotective effects on immune cells and other normal cells are important in promoting a TIME that favors anti-tumor immunity. As a result, DIM increases the efficacy of radiation treatment on tumor regression. This study supports the development of DIM as an adjunct agent for radiation treatment. Citation Format: Renxiang Chen, Lijun Li, Yun-Tien Lin, Arslon Humayun, Albert J. Fornace Jr., Heng-Hong Li. 3,39-diindolylmethane enhances tumor regression after radiation through protecting normal cells to modulate anti-tumor immunity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6513.