Back to Search
Start Over
Breast Cancer Cells and PD-1/PD-L1 Blockade Upregulate the Expression of PD-1, CTLA-4, TIM-3 and LAG-3 Immune Checkpoints in CD4+ T Cells.
- Source :
- Vaccines; Dec2019, Vol. 7 Issue 4, p149-149, 1p
- Publication Year :
- 2019
-
Abstract
- Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and it exhibits resistance to common breast cancer therapies. Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and its ligand, PD-L1, have been approved to treat various cancers. However, the therapeutic efficacy of targeting PD-1/PD-L1 axis in breast cancer is under clinical investigation. In addition, the mechanisms of action of drugs targeting PD-1 and PD-L1 have not been fully elucidated. In this study, we investigated the effect of human TNBC cell lines, MDA-MB-231 and MDA-MB-468, and the non-TNBC cell line, MCF-7, on the expression of immune checkpoints (ICs) on CD4<superscript>+</superscript> T cell subsets, including regulatory T cells (Tregs), using a co-culture system. We also examined the effect of blocking PD-1 or PD-L1 separately and in combination on IC expression by CD4<superscript>+</superscript> T cell subsets. We found that breast cancer cells upregulate the expression of ICs including PD-1, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and lymphocyte activation gene-3 (LAG-3) in CD4<superscript>+</superscript> T cell subsets. We also found that the co-blockade of PD-1 and PD-L1 further upregulates the co-expression of TIM-3 and LAG-3 on CD4<superscript>+</superscript>CD25<superscript>+</superscript> T cells and CD4<superscript>+</superscript>CD25<superscript>+</superscript>FoxP3<superscript>+</superscript>Helios<superscript>+</superscript> Tregs in the presence of TNBC cells, but not in non-TNBC cells. Our results indicate the emergence of compensatory inhibitory mechanisms, most likely mediated by Tregs and activated non-Tregs, which could lead to the development of TNBC resistance against PD-1/PD-L1 blockade. [ABSTRACT FROM AUTHOR]
- Subjects :
- T cells
CANCER cells
SUPPRESSOR cells
TRIPLE-negative breast cancer
BREAST cancer
Subjects
Details
- Language :
- English
- ISSN :
- 2076393X
- Volume :
- 7
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Vaccines
- Publication Type :
- Academic Journal
- Accession number :
- 140903482
- Full Text :
- https://doi.org/10.3390/vaccines7040149