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Single-cell RNA-seq reveals the metabolic status of immune cells response to immunotherapy in triple-negative breast cancer.
Liu, Pei-Wen; Lin, Jun; Hou, Rui; Cai, Zhe; Gong, Yue; He, Ping-An; Yang, Jialiang.
Afiliación
  • Liu PW; School of Science, Zhejiang Sci-Tech University, Hangzhou, China; Geneis Beijing Co., Ltd., Beijing, China.
  • Lin J; Depatment of Pathology, The People's Hospital of QuZhou City, ZheJiang, China.
  • Hou R; Geneis Beijing Co., Ltd., Beijing, China.
  • Cai Z; Extendcity (Shanghai) Co., Ltd., Shanghai, China.
  • Gong Y; Geneis Beijing Co., Ltd., Beijing, China.
  • He PA; School of Science, Zhejiang Sci-Tech University, Hangzhou, China. Electronic address: pinganhe@zstu.edu.cn.
  • Yang J; Geneis Beijing Co., Ltd., Beijing, China. Electronic address: yangjl@geneis.cn.
Comput Biol Med ; 169: 107926, 2024 Feb.
Article en En | MEDLINE | ID: mdl-38183706
ABSTRACT
Immune checkpoint blockade (ICB) therapy offers promise in the treatment of triple-negative breast cancer (TNBC); however, its limited efficacy in certain TNBC patients poses a challenge. In this study, we elucidated the metabolic mechanism at 'sub-subtype' resolution underlying the non-response to ICB therapy in TNBC. Here, an analytic pipeline was developed to reveal the metabolic heterogeneity, which is correlated with the ICB outcomes, within each immune cell subtype. First, we identified metabolic 'sub-subtypes' within certain cell subtypes, predominantly T cell subsets, which are enriched in ICB non-responders and named as non-responder-enriched (NR-E) clusters. Notably, most of NR-E T metabolic cells exhibit globally higher metabolic activities compared to other cells within the same individual subtype. Further, we investigated the extra-cellular signals that trigger the metabolic status of NR-E T cells. In detail, the prediction of cell-to-cell communication indicated that NR-E T cells are regulated by plasmatic dendritic cells (pDCs) through TNFSF9, as well as by macrophages expressing SIGLEC9. In addition, we also validate the communication between TNFSF9+ pDCs and NR-E T cells utilizing deconvolution of spatial transcriptomics analysis. In summary, our research identified specific metabolic 'sub-subtypes' associated with ICB non-response and uncovered the mechanisms of their regulation in TNBC. And the proposed analytical pipeline can be used to examine metabolic heterogeneity within cell types that correlate with diverse phenotypes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Comput Biol Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Comput Biol Med Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos