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- W4381330901 abstract "BRCA1 mutation is reported in about 70% of all triple negative breast cancers (TNBC), while BRCA1 defect due to promoter hypermethylation is seen in about 30%-60% of sporadic breast cancers. Although PARP inhibitors and platinum-based chemotherapy are used to treat these cancers, more efficient therapeutic approaches are required to overcome the resistance to treatment. Our previous findings have reported elevated βhCG expression but not αhCG in BRCA1 deficient breast cancers. As βhCG causes immune suppression in pregnancy, this study explored the immunomodulatory effect of βhCG in BRCA1mutated/deficient TNBC. We observed that Th1, Th2, and Th17 cytokines are upregulated in the presence of βhCG in BRCA1 defective cancers. In NOD-SCID and syngeneic mouse models, βhCG increases the frequency of Myeloid-derived suppressor cells in tumour tissues and contributes to macrophage reprogramming from antitumor M1 to pro-tumour M2 phenotype. βhCG reduces the CD4+ T-cell infiltration while increasing the density of CD4+ CD25+ FOXP3+ regulatory T-cell in BRCA1 deficient tumour tissues. In contrast, xenograft tumours with βhCG knocked down TNBC cells did not show these immune suppressive effects. We have also shown that βhCG upregulates pro-tumorigenic markers arginase1(Arg1), inducible nitric oxide synthase, PD-L1/PD-1, and NFκB in BRCA1 defective tumours. Thus, for the first time, this study proves that βhCG suppresses the host antitumor immune response and contributes to tumour progression in BRCA1 deficient tumours. This study will help develop new immunotherapeutic approaches for treating BRCA1 defective TNBC by regulating βhCG." @default.
- W4381330901 created "2023-06-21" @default.
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- W4381330901 date "2023-06-20" @default.
- W4381330901 modified "2023-10-17" @default.
- W4381330901 title "<scp>βhCG</scp> mediates immune suppression through upregulation of <scp>CD11b</scp><sup>+</sup>Gr1<sup>+</sup> myeloid derived suppressor cells, <scp>CD206</scp><sup>+</sup><scp>M2</scp> macrophages, and <scp>CD4</scp><sup>+</sup><scp>FOXP3</scp><sup>+</sup> regulatory T‐cells in <scp>BRCA1</scp> deficient breast cancers" @default.
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- W4381330901 doi "https://doi.org/10.1111/imm.13673" @default.
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