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IDO Inhibition Facilitates Antitumor Immunity of Vγ9Vδ2 T Cells in Triple-Negative Breast Cancer
- Source :
- Frontiers in Oncology, Frontiers in Oncology, Vol 11 (2021)
- Publication Year :
- 2021
- Publisher :
- Frontiers Media SA, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
T cell
anti-tumor immunity
1-Methyl-L-tryptophan
IDO
03 medical and health sciences
0302 clinical medicine
Breast cancer
Medicine
Perforin production
Receptor
Cytotoxicity
RC254-282
γδT cell
perforin
Triple-negative breast cancer
Original Research
biology
business.industry
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
Immune checkpoint
030104 developmental biology
medicine.anatomical_structure
Oncology
Perforin
Cancer research
biology.protein
business
030215 immunology
Subjects
Details
- ISSN :
- 2234943X
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Oncology
- Accession number :
- edsair.doi.dedup.....e17de44382acdd757347a0412177be09
- Full Text :
- https://doi.org/10.3389/fonc.2021.679517