Single-Cell Transcriptomic Analysis Reveals the Crosstalk Propensity Between the Tumor Intermediate State and the CD8+ T Exhausted State to be Associated with Clinical Benefits in Melanoma.
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| Abstract |
Heterogeneous crosstalk between tumor cells and CD8+ T cells leads to substantial variation in clinical benefits from immunotherapy in melanoma. Due to spatial distribution and functional state heterogeneity, it is still unknown whether there is a crosstalk propensity between tumor cells and CD8+ T cells in melanoma, and how this crosstalk propensity affects the clinical outcome of patients. Using public single-cell transcriptome data, extensive heterogeneous functional states and ligand-receptor interactions of tumor cells and CD8+ T cells were revealed in melanoma. Furthermore, based on the association between cell-cell communication intensity and cell state activity in a single cell, we identified a crosstalk propensity between the tumor intermediate state and the CD8+ T exhausted state. This crosstalk propensity was further verified by pseudo-spatial proximity, spatial co-location, and the intra/intercellular signal transduction network. At the sample level, the tumor intermediate state and the CD8+ T exhausted state synergistically indicated better prognosis and both reduced in immunotherapy-resistant samples. The risk groups defined based on these two cell states could comprehensively reflect tumor genomic mutations and anti-tumor immunity information. The low-risk group had a higher BRAF mutation fraction as well as stronger antitumor immune response. Our findings highlighted the crosstalk propensity between the tumor intermediate state and the CD8+ T exhausted state, which may serve as a reference to guide the development of diagnostic biomarkers for risk stratification and therapeutic targets for new therapeutic strategies.
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| Authors | Jiali Zhu, Min Yan, Haoteng Yan, Liwen Xu, Zedong Jiang, Gaoming Liao, Yao Zhou, Wei Liu, Xin Liang, Xia Li, Yun Xiao, Yunpeng Zhang |
| Journal | Frontiers in immunology (Front Immunol) Vol. 13 Pg. 766852 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland |
| PMID | 35903095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 Zhu, Yan, Yan, Xu, Jiang, Liao, Zhou, Liu, Liang, Li, Xiao and Zhang. |
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