Cargando…

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

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Peng, Wu, Ruan, Li, Ke, Yuan, Wenhui, Zeng, Chuqian, Zhang, Yuting, Wang, Xiao, Zhu, Xinhai, Zhou, Jianjun, Li, Ping, Gao, Yunfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351331/
https://www.ncbi.nlm.nih.gov/pubmed/34381711
http://dx.doi.org/10.3389/fonc.2021.679517
_version_ 1783735952146956288
author Li, Peng
Wu, Ruan
Li, Ke
Yuan, Wenhui
Zeng, Chuqian
Zhang, Yuting
Wang, Xiao
Zhu, Xinhai
Zhou, Jianjun
Li, Ping
Gao, Yunfei
author_facet Li, Peng
Wu, Ruan
Li, Ke
Yuan, Wenhui
Zeng, Chuqian
Zhang, Yuting
Wang, Xiao
Zhu, Xinhai
Zhou, Jianjun
Li, Ping
Gao, Yunfei
author_sort Li, Peng
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8351331
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83513312021-08-10 IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer Li, Peng Wu, Ruan Li, Ke Yuan, Wenhui Zeng, Chuqian Zhang, Yuting Wang, Xiao Zhu, Xinhai Zhou, Jianjun Li, Ping Gao, Yunfei Front Oncol Oncology 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. Frontiers Media S.A. 2021-07-22 /pmc/articles/PMC8351331/ /pubmed/34381711 http://dx.doi.org/10.3389/fonc.2021.679517 Text en Copyright © 2021 Li, Wu, Li, Yuan, Zeng, Zhang, Wang, Zhu, Zhou, Li and Gao https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Li, Peng
Wu, Ruan
Li, Ke
Yuan, Wenhui
Zeng, Chuqian
Zhang, Yuting
Wang, Xiao
Zhu, Xinhai
Zhou, Jianjun
Li, Ping
Gao, Yunfei
IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title_full IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title_fullStr IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title_full_unstemmed IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title_short IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
title_sort ido inhibition facilitates antitumor immunity of vγ9vδ2 t cells in triple-negative breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351331/
https://www.ncbi.nlm.nih.gov/pubmed/34381711
http://dx.doi.org/10.3389/fonc.2021.679517
work_keys_str_mv AT lipeng idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT wuruan idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT like idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT yuanwenhui idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT zengchuqian idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT zhangyuting idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT wangxiao idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT zhuxinhai idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT zhoujianjun idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT liping idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer
AT gaoyunfei idoinhibitionfacilitatesantitumorimmunityofvg9vd2tcellsintriplenegativebreastcancer