Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer.

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38201582", "kind": "science-record", "revision": 2, "content_hash": "sha256:1dac48fd9e577df70e34ded199f3ad89c982345536346b281f7eda0406482b8a", "created_at": "2026-11-01T19:20:07Z", "updated_at": "2026-11-01T21:32:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Ferroptosis Inducers Upregulate PD-L1 in Recurrent Triple-Negative Breast Cancer.", "doi": "10.3390/cancers16010155", "pmid": "38201582", "authors": ["Christophe Desterke", "Yao Xiang", "Rima Elhage", "Clémence Duruel", "Yunhua Chang", "Ahmed Hamaï"], "journal": "Cancers", "year": 2023, "abstract": "(1) Background: Triple-negative breast cancer (TNBC) is a distinct subgroup of breast cancer presenting a high level of recurrence, and neo-adjuvant chemotherapy is beneficial in its therapy management. Anti-PD-L1 immunotherapy improves the effect of neo-adjuvant therapy in TNBC. (2) Methods: Immune-modulation and ferroptosis-related R-packages were developed for integrative omics analyses under ferroptosis-inducer treatments: TNBC cells stimulated with ferroptosis inducers (GSE173905, GSE154425), single cell data (GSE191246) and mass spectrometry on breast cancer stem cells. Clinical association analyses were carried out with breast tumors (TCGA and METABRIC cohorts). Protein-level validation was investigated through protein atlas proteome experiments. (3) Results: Erastin/RSL3 ferroptosis inducers upregulate CD274 in TNBC cells (MDA-MB-231 and HCC38). In breast cancer, CD274 expression is associated with overall survival. Breast tumors presenting high expression of CD274 upregulated some ferroptosis drivers associated with prognosis: IDO1, IFNG and TNFAIP3. At the protein level, the induction of Cd274 and Tnfaip3 was confirmed in breast cancer stem cells under salinomycin treatment. In a 4T1 tumor treated with cyclophosphamide, the single cell expression of Cd274 was found to increase both in myeloid- and lymphoid-infiltrated cells, independently of its receptor Pdcd1. The CD274 ferroptosis-driver score computed on a breast tumor transcriptome stratified patients on their prognosis: low score was observed in the basal subgroup, with a higher level of recurrent risk scores (oncotypeDx, ggi and gene70 scores). In the METABRIC cohort, CD274, IDO1, IFNG and TNFAIP3 were found to be overexpressed in the TNBC subgroup. The CD274 ferroptosis-driver score was found to be associated with overall survival, independently of TNM classification and age diagnosis. The tumor expression of CD274, TNFAIP3, IFNG and IDO1, in a biopsy of breast ductal carcinoma, was confirmed at the protein level (4) Conclusions: Ferroptosis inducers upregulate PD-L1 in TNBC cells, known to be an effective target of immunotherapy in high-risk early TNBC patients who received neo-adjuvant therapy. Basal and TNBC tumors highly expressed CD274 and ferroptosis drivers: IFNG, TNFAIP3 and IDO1. The CD274 ferroptosis-driver score is associated with prognosis and to the risk of recurrence in breast cancer. A potential synergy of ferroptosis inducers with anti-PD-L1 immunotherapy is suggested for recurrent TNBC.", "claims": [{"id": "claim-method", "statement": "This Cox multivariable model was performed with the inclusion of score stratification (Table 2), age at diagnosis stratification (threshold 65 years old) and TNM stage classification.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38201582", "locator": "sections[21] \"3.4. CD274 Ferroptosis-Driver Score Is an Independent Prognosis Marker in Breast Cancer Overall Survival\" paragraph 2", "quote": "This Cox multivariable model was performed with the inclusion of score stratification (Table 2), age at diagnosis stratification (threshold 65 years old) and TNM stage classification."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Recurrent scores for breast cancer computed on TCGA invasive breast cohort were shared as eset metadata of experiment assay in a R-package available online (tcga.breast): https://figshare.com/articles/software/R_package_composed_of_eset_RNAseq_-_TCGA_breast_cancer_with_clinical_scores_computed_/24083388/1; accepted date 22 December 2023, DOI: 10.6084/M9.FIGSHARE.24083388.V1. Specific R-packages designed for this article were deposited on github for a direct installation via devtools. It concerned “immunemod” package for immune modulation transcriptome study: https://github.com/cdesterke/immunemod, and ferroviz for ferroptosis transcriptome investigations: https://github.com/cdesterke/ferroviz.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38201582", "locator": "sections[30] \"notes\" paragraph 1", "quote": "Recurrent scores for breast cancer computed on TCGA invasive breast cohort were shared as eset metadata of experiment assay in a R-package available online (tcga.breast): https://figshare.com/articles/software/R_package_composed_of_eset_RNAseq_-_TCGA_breast_cancer_with_clinical_scores_computed_/24083388/1; accepted date 22 December 2023, DOI: 10.6084/M9.FIGSHARE.24083388.V1. Specific R-packages designed for this article were deposited on github for a direct installation via devtools. It concerned “immunemod” package for immune modulation transcriptome study: https://github.com/cdesterke/immunemod, and ferroviz for ferroptosis transcriptome investigations: https://github.com/cdesterke/ferroviz."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A high CD274 ferroptosis-driver score was an adverse independent prognostic marker for overall survival in breast cancer, with a multivariable hazard ratio of 2.012 ± 1.063 and a multivariable p-value of 3.18 × 10−2.", "kind": "quantitative", "target": {"value": 3.18, "unit": "p-value", "tolerance": null, "source": "In the multivariate overall survival model, patients quantified with a high value of the CD274 ferroptosis-driver score harbored a significant positive hazard ratio (2.012 ± 1.063, multivariable p-value = 3.18 × 10−2, Table 3, Figure 9A)."}, "evidence": [{"asset": "source:pmid:38201582", "locator": "sections[21] \"3.4. 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