In:
Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-10-31)
Abstract:
Due to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level. Methods A mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice. Results CKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8 + T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8 + T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro . Conclusions The combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2022.965342
DOI:
10.3389/fimmu.2022.965342.s001
DOI:
10.3389/fimmu.2022.965342.s002
DOI:
10.3389/fimmu.2022.965342.s003
DOI:
10.3389/fimmu.2022.965342.s004
DOI:
10.3389/fimmu.2022.965342.s005
DOI:
10.3389/fimmu.2022.965342.s006
DOI:
10.3389/fimmu.2022.965342.s007
DOI:
10.3389/fimmu.2022.965342.s008
DOI:
10.3389/fimmu.2022.965342.s009
DOI:
10.3389/fimmu.2022.965342.s010
DOI:
10.3389/fimmu.2022.965342.s011
DOI:
10.3389/fimmu.2022.965342.s012
DOI:
10.3389/fimmu.2022.965342.s013
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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