AUTHOR=Liu Xinkui , Bai Meirong , Li Huiying , Ye Peizhi , Duan Xiaoxia , Wu Chao , Huang Zhihong , Lu Shan , Zhang Jingyuan , Zhao Zihan , Guo Fengying , You Rongli , Qin Wenjie , Wang Wei , Han Aiqing , Shen Liangliang , Wang Yitao , Zhao Zheng , Luo Hua , Wu Jiarui 

TITLE=Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.965342

DOI=10.3389/fimmu.2022.965342

ISSN=1664-3224

ABSTRACT=Background: 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. Bulk and single cell RNA-sequencing (scRNA-seq) were used 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 study displayed a significantly higher activation of T lymphocytes and natural killer (NK) cells 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 T and NK cells, inhibit tumor-promoting signaling pathways, and activate immune-related biological processes. 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 antitumor effect of chemotherapy by activating immune cells to suppress tumors in TNBC mice.