e19066 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, accounting for more than 30% of all cases. Although with the development of treatment, the 5 years overall survival rates remain low, range from 30%-50% for all DLBCL patients. In addition to R-CHOP, immunotherapy has attracted much attention. However, the single-agent activity of most immune checkpoint inhibitors (ICI) in DLBCL has been overwhelmingly disappointing. It is urgent to develop new methods to enhance the efficacy of DLBCL treatment. Our previous study demonstrated that 1-L-MT, an IDO1 inhibitor, can inhibit tumor growth of DLBCL. Here, we investigate whether 1-L-MT promotes antitumor immunity of ICI in DLBCL. Methods: The role of 1-L-MT on cell proliferation in vitro and tumor growth in NOD/SCID mice were investigated. RNA-seq analysis was performed in 1-L-MT treated and control OCI-Ly10 cells. ChIP assay was performed using AhR-precipitated DNA samples of OCI-Ly10 cells (treated with or without 1-L-MT) and primers for PD-L1, and he expression of PD-L1 was evaluated by RT-qPCR. The combination of 1-L-MT and PD-1 blockade therapy were performed in C57BL/6 mouse bearing tumor cells to evaluate the antitumor activity. Results: In our study, IDO1 inhibitor 1-L-MT sensitized diffuse large B cell lymphoma to immunotherapy via downregulation of PD-L1. Further study confirmed that 1-L-MT could reduce the expression of PD-L1 and upregulate the expression of MHC-I antigen presentation factors. In addition, RNA-seq and bioinformatics analysis revealed that the transcription factor AhR may involved in the downregulation of PD-L1 transcription level induced by 1-L-MT. Mechanistically, ChIP and RT-qPCR assays were conducted to test AhR-PD-L1 interaction, and the results showed that AhR directly bound the promoter of PD-L1. 1-L-MT-mediated PD-L1 reduction promoted T cell activation and T cell killing of tumor cells. The combination of 1-L-MT and anti PD-1 antibody significantly inhibited DLBCL growth and extends the lifespan of tumor-bearing mice. Conclusions: Our study unveiled a mechanism by which 1-L-MT induces PD-L1 downregulation via AhR and provides methods to facilitate immunotherapy in diffuse large B-cell lymphoma. The present study may provide a theoretical foundation for overcoming the challenge of low-sensitivity to immunotherapy in DLBCL.