期刊
ONCOIMMUNOLOGY
卷 6, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1263412
关键词
Breast cancer; epithelial-to-mesenchymal transition; miR-200 and; immunotherapy; PD-L1; SLUG (SNAI2); SNAI1; ZEB-1
资金
- GEFLUC [R15079LL]
- Equipe labellis lisee par la Ligue Contre le Cancer [EL2015.LNCC/SaC]
- FNRS-Televie [7.4664.15]
- LIH, Luxembourg [2013 11 05]
- INCA for an INCA [PLBIO15-266]
PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7-1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1-6SA cells. Mechanistic investigations revealed that siRNA silencing of ZEB-1, but not SNAI1, TWIST, or SLUG and overexpression of miR200 family members in MCF7 sh-WISP2 cells strongly decreased PD-L1 expression. Thus, we propose that PD-L1 expression in EMT-activated breast cancer cells depends on the EMT-TF involved in EMT activation. Interestingly, siRNA-mediated targeting of PD-L1 or anti-bodymediated PD-L1 block restored the susceptibility of highly resistant MCF7 sh-WISP2 and MCF7-2101 cells to CTL-mediated killing. Additionally, these results provide a novel preclinical rationale to explore EMT inhibitors as adjuvants to boost immunotherapeutic responses in subgroups of patients in whom malignant progression is driven by different EMT-TFs.
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