AUTHOR=Zhu Jiali , Yan Min , Yan Haoteng , Xu Liwen , Jiang Zedong , Liao Gaoming , Zhou Yao , Liu Wei , Liang Xin , Li Xia , Xiao Yun , Zhang Yunpeng TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.766852 DOI=10.3389/fimmu.2022.766852 ISSN=1664-3224 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.