| Autor: |
Md Shakir Uddin Ahmed, Brittany D. Lord, Benjamin Adu Addai, Sandeep K. Singhal, Kevin Gardner, Ahmad Bin Salam, Anghesom Ghebremedhin, Jason White, Iqbal Mahmud, Rachel Martini, Deepa Bedi, Huixian Lin, Jacqueline D. Jones, Balasubramanyanam Karanam, Windy Dean-Colomb, William Grizzle, Honghe Wang, Melissa Davis, Clayton C. Yates |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Cancers; Volume 15; Issue 8; Pages: 2282 |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers15082282 |
| Popis: |
African American (AA) women with breast cancer are more likely to have higher inflammation and a stronger overall immune response, which correlate with poorer outcomes. In this report, we applied the nanostring immune panel to identify differences in inflammatory and immune gene expression by race. We observed a higher expression of multiple cytokines in AA patients compared to EA patients, with high expression of CD47, TGFB1, and NFKB1 associated with the transcriptional repressor Kaiso. To investigate the mechanism associated with this expression pattern, we observed that Kaiso depletion results in decreased expression of CD47, and its ligand SIRPA. Furthermore, Kaiso appears to directly bind to the methylated sequences of the THBS1 promotor and repress gene expression. Similarly, Kaiso depletion attenuated tumor formation in athymic nude mice, and these Kaiso-depleted xenograft tissues showed significantly higher phagocytosis and increased infiltration of M1 macrophages. In vitro validation using MCF7 and THP1 macrophages treated with Kaiso-depleted exosomes showed a reduced expression of immune-related markers (CD47 and SIRPA) and macrophage polarization towards the M1 phenotype compared to MCF7 cells treated with exosomes isolated from high-Kaiso cells. Lastly, analysis of TCGA breast cancer patient data demonstrates that this gene signature is most prominent in the basal-like subtype, which is more frequently observed in AA breast cancer patients. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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