3,3′-Diindolylmethane improves antitumor immune responses of PD-1 blockade via inhibiting myeloid-derived suppressor cells

• DOI: 10.1186/s13020-022-00638-z
• Publication Date: 2022-06-30T04:02:40Z
• Authors: Qi Sun; Lin Xiao; Zhiying Cui; Yaping Yang; Junting Ma; Zhen Huang; Junfeng Zhang; Jiangning Chen
• Keywords: Myeloid-derived Suppressor Cell; Cancer Immunotherapy

Immune checkpoint inhibitors that target programmed cell death protein 1 (PD-1) have obtained encouraging results, but a fraction of tumor patients failed to respond anti-PD-1 treatment due the existence multiple immune suppressive elements such as myeloid-derived suppressor cells (MDSCs). Traditional Chinese medicine or natural products from medicinal plants could enhance immunity and may be helpful for cancer immunotherapy. As digestive metabolite cruciferous plants, 3,3'-diindolylmethane (DIM) has been widely used in chemotherapy, its influence on immunotherapy remains unclear. Here we investigate function DIM MDSCs examine therapeutic effects conjunction with PD-1 antibody against mouse tumors.Flow cytometry analysis, Western blot analysis qRT-PCR assay were inhibitory mechanisms vitro vivo. The by evaluated models breast melanoma tumor.DIM exerted effect via downregulating miR-21 level subsequently activating PTEN/PIAS3-STAT3 pathways. Adoptive transfer impaired DIM, indicating antitumor activity might suppression MDSCs. Furthermore, tumor, addition can through promoting T responses, thereby inhibiting growth.Overall, strategy based combination provide new approach Cruciferae plants-rich diet which contains high amount precursor beneficial undergo treatment.