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All-Trans Retinoic Acid Stimulates Viral Mimicry, Interferon Responses and Antigen Presentation in Breast-Cancer Cells.
- Source :
- Cancers; May2020, Vol. 12 Issue 5, p1169, 1p
- Publication Year :
- 2020
-
Abstract
- All-trans retinoic acid (ATRA), a recognized differentiating agent, has significant potential in the personalized/stratified treatment of breast cancer. The present study reports on the molecular mechanisms underlying the anti-tumor activity of ATRA in breast cancer. The work is based on transcriptomic experiments performed on ATRA-treated breast cancer cell-lines, short-term tissue cultures of patient-derived mammary-tumors and a xenograft model. ATRA upregulates gene networks involved in interferon-responses, immune-modulation and antigen-presentation in retinoid-sensitive cells and tumors characterized by poor immunogenicity. ATRA-dependent upregulation of these gene networks is caused by a viral mimicry process, involving the activation of endogenous retroviruses. ATRA induces a non-canonical type of viral mimicry, which results in increased expression of the IRF1 (Interferon Responsive Factor 1) transcription factor and the DTX3L (Deltex-E3-Ubiquitin-Ligase-3L) downstream effector. Functional knockdown studies indicate that IRF1 and DTX3L are part of a negative feedback loop controlling ATRA-dependent growth inhibition of breast cancer cells. The study is of relevance from a clinical/therapeutic perspective. In fact, ATRA stimulates processes controlling the sensitivity to immuno-modulatory drugs, such as immune-checkpoint-inhibitors. This suggests that ATRA and immunotherapeutic agents represent rational combinations for the personalized treatment of breast cancer. Remarkably, ATRA-sensitivity seems to be relatively high in immune-cold mammary tumors, which are generally resistant to immunotherapy. [ABSTRACT FROM AUTHOR]
- Subjects :
- ANTINEOPLASTIC agents
BIOCHEMISTRY
BREAST tumors
CANCER patients
CELL lines
CELL receptors
CHALONES
DRUG resistance in cancer cells
IMMUNE system
IMMUNOTHERAPY
INTERFERONS
PHENOMENOLOGY
RESEARCH methodology
MOLECULAR biology
RETROVIRUSES
TISSUE culture
TRANSCRIPTION factors
TRETINOIN
TUMOR antigens
XENOGRAFTS
INDIVIDUALIZED medicine
GENE expression profiling
PHARMACODYNAMICS
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 12
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Cancers
- Publication Type :
- Academic Journal
- Accession number :
- 143673972
- Full Text :
- https://doi.org/10.3390/cancers12051169