Desterke, C.; Xiang, Y.; Elhage, R.; Duruel, C.; Chang, Y.; Hamaï, A. Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer. Cancers2024, 16, 155.
Desterke, C.; Xiang, Y.; Elhage, R.; Duruel, C.; Chang, Y.; Hamaï, A. Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer. Cancers 2024, 16, 155.
Desterke, C.; Xiang, Y.; Elhage, R.; Duruel, C.; Chang, Y.; Hamaï, A. Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer. Cancers2024, 16, 155.
Desterke, C.; Xiang, Y.; Elhage, R.; Duruel, C.; Chang, Y.; Hamaï, A. Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer. Cancers 2024, 16, 155.
Abstract
(1) Background: Triple negative breast cancer (TNBC) is a distinct subgroup of breast cancer presenting high level of recurrence and neo-adjuvant chemotherapy is beneficial in its therapy management. Anti-PD-L1 immunotherapy improves effect of neo-adjuvant therapy in TNBC. (2) Methods: Immune-modulation and ferroptosis related R-packages were developed for integrative transcriptome to analyze transcriptome datasets: TNBC cells stimulated with ferroptosis inducers (GSE173905, GSE154425), breast tumors with clinical data (TCGA and METABRIC cohorts). Protein level validation was investigated through protein atlas proteome experiments. (3) Results: Erastin/RSL3 ferroptosis inducers up-regulate CD274 in TNBC cells (MDA-MB-231 and HCC38). In breast cancer, CD274 expression is associated to overall survival. Breast tumors presenting high expression of CD274 up-regulated some ferroptosis drivers associated to prognosis: IDO1, IFNG and TNFAIP3. CD274-ferroptosis-driver score computed on breast tumor transcriptome stratified patients on their prognosis: low score was observed in basal subgroup with higher level of recurrent risk scores: oncotypeDx, ggi and gene70 scores. In METABRIC cohort, CD274, IDO1, IFNG and TNFAIP3 were found overexpressed in TNBC subgroup. CD274-ferroptosis-driver score was found associated to overall survival independently of TNM classification and age diagnosis. Tumor expression of CD274, TNFAIP3, IFNG and IDO1 in biopsy of breast ductal carcinoma was confirmed at protein level (4) Conclusion: Ferroptosis inducers up-regulate PD-L1 in TNBC cells, known as effective target of immunotherapy in high risk early TNBC which received neo-adjuvant therapy. Basal and TNBC tumors highly expressed CD274 and ferroptosis drivers: IFNG, TNFAIP3 and IDO1. CD274-ferroptosis driver score is associated to prognosis and to the risk of recurrence in breast cancer. A potential synergy of ferroptosis inducers with anti-PD-L1 immunotherapy is suggested in recurrent TNBC.
Keywords
CD274; ferroptosis; immunotherapy; breast cancer; basal; TNBC
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
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