IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer.

Abstract

Triple-negative breast cancer (TNBC) escape from immune-mediated destruction was associated with immunosuppressive responses that dampened the activation of tumor-infiltrating CD8 and γδ T cells. TNBC had a higher level of programmed cell death 1-ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO), compared with other breast cancer subtypes. But, clinical studies have revealed that the response rate of PD-1/PD-L1 antibody for TNBC treatment was relatively low. However, the antitumor responses of human Vγ9Vδ2 T cells or IDO inhibitor in TNBC treatment are unknown. In this study, we found that IDO1 and PD-L1 were highly expressed in TNBC patients. Analysis of the clinical samples demonstrated that Vγ9Vδ2 T cells became exhausted in triple-negative breast cancer patients. And Vγ9Vδ2 T cells combined with αPD-L1 could not further enhance their antitumor responses in vitro and in vivo. However, Vγ9Vδ2 T cells combined with IDO1 inhibitor 1-Methyl-L-tryptophan (1-MT) or Lindrostat showed substantial inhibitory effects on MDA-MB-231 tumor cells. Finally, we found that IDO1 inhibitor promoted T cell's cytotoxicity by enhancing perforin production. These results converged to suggest the potential application of Vγ9Vδ2 T cells treated with IDO1 inhibitor for TNBC therapy.

• Authors: Peng Li, Ruan Wu, Ke Li, Wenhui Yuan, Chuqian Zeng, Yuting Zhang, Xiao Wang, Xinhai Zhu, Jianjun Zhou, Ping Li, Yunfei Gao
• Journal: Frontiers in oncology (Front Oncol) Vol. 11 Pg. 679517 ( 2021) ISSN: 2234-943X [Print] Switzerland
• PMID: 34381711 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Li, Wu, Li, Yuan, Zeng, Zhang, Wang, Zhu, Zhou, Li and Gao.