IDO-1 通过上调 HLA-G 损害三阴性乳腺癌中 NK 细胞的抗肿瘤免疫

Triple-negative breast cancers (TNBC) are highly aggressive malignancies with poor prognosis. As an essential enzyme in the tryptophan-kynurenine metabolic pathway, indoleamine 2,3 dioxygenase-1 (IDO-1) has been reported to facilitate immune escape of various tumors. However, the mechanism underlying the immunosuppressive role of IDO-1 in TNBC remains largely uncharacterized.

We examined the IDO-1 expression in 93 clinical TNBC tissues and paired adjacent normal tissues, and analyzed the regulation role of environmental cytokines like IFN- in IDO-1 expression. The effect of IDO-1 expression in TNBC cells on the function of NK cells were then evaluated and the underlying mechanisms were exploited.

IDO-1 expressed in 50 of 93 (54.1%) TNBC patients. TNBC patients with high IDO-1 expression tended to have more infiltrated immune cells including NK cells, which are less active than patients with low IDO-1 expression. NK cells could produce IFN- , which induced IDO-1 expression in TNBC cells, whereas IDO-1 impaired the cytotoxicity of co-cultured NK cells by upregulation of HLA-G. Blockade of HLA-G improved the antitumor activity of NK cells to TNBC in vivo.

TNBC cells induce dysfunction of NK cells through an IFN- /IDO-1/HLA-G pathway, which provide novel insights into the mechanisms of TNBC progression and demonstrate the applicability of IDO-1 and HLA-G targeting in the treatment of TNBC.