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Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy combined with anti-EGFR antibodies [Nanostring]

ABSTRACT: To find metastatic recurrence biomarkers of triple negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180717 | GEO | 2021/07/26

REPOSITORIES: GEO

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Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy combined with anti-EGFR antibodies [Agilent]

Project description:To find metastatic recurrence biomarkers of triple negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.

2021-07-28 | GSE180775 | GEO

Downregulation of antigen presentation-associated pathway proteins in poor outcome triple-negative breast cancer patient tumors

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2018-10-26 | PXD005544 | Pride

Project description:Recurrence biomarkers of TNBC

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Metabolic and lipidomic characterization of radioresistant MDA-MB-231 human breast cancer cells to investigate potential therapeutic targets

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2021-09-22 | ST001920 | MetabolomicsWorkbench

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2021-10-31 | E-MTAB-8760 | biostudies-arrayexpress

Rapid CLIP Dissociation from MHC II Promotes an Unusual Antigen Presentation Pathway in Autoimmunity

Project description:A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated b57 polymorphism. We generated knock-in Non-obese Diabetic (NOD) mice with a single amino acid change in the CLIP segment of invariant chain in order to moderately slow CLIP dissociation from I-Ag7. These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within b cell secretory granules. Rapid CLIP dissociation enhanced presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.

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Transcriptoma analysis of B splenocytes of 3'RR-deficient mice and wt mice

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2014-01-15 | E-GEOD-45230 | biostudies-arrayexpress

Inhibition of the CtBP complex and FBXO11 enhances MHC class II expression and anti-cancer immune responses [Whole-genome CRISPRscreen]

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