Targeting tryptophan catabolic kynurenine pathway enhances antitumor immunity and cytotoxicity in multiple myeloma.

ABSTRACT: Our prior studies showed that dysfunctional plasmacytoid dendritic cells (pDCs) contribute to multiple myeloma (MM) pathogenesis. Specifically, pDC interactions with tumor and T/NK effector cells in the bone marrow (BM) milieu induce immune suppression and MM cell proliferation. Delineation of the mechanism(s) mediating pDC-MM-T-NK cell interactions will identify novel therapeutic targets to both enhance cytotoxicity and anti-MM immunity. Here, we utilized gene expression profiling (GEP) to show that pDC-MM interactions trigger upregulation of immunosuppressive tryptophan catabolic kynurenine (Kyn) pathway. In particular, we show that Kyn pathway enzyme kynurenine-3-monooxygenase (KMO) is upregulated during pDC-MM interactions. Using our coculture models of patient autologous pDC-T-NK-MM c

SUBMITTER: Ray A 

PROVIDER: S-EPMC7132142 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature