Trajectory and Functional Analysis of PD-1^high CD4⁺CD8⁺ T Cells in Hepatocellular Carcinoma by Single-Cell Cytometry and Transcriptome Sequencing.

ABSTRACT: The spatial heterogeneity of immune microenvironment in hepatocellular carcinoma (HCC) remains elusive. Here, a single-cell study involving 17 432 600 immune cells of 39 matched HCC (T), nontumor (N), and leading-edge (L) specimens by mass cytometry is conducted. The tumor-associated CD4/CD8 double-positive T (DPT) cells are found enriched in L regions with synergetic expression of PD-1/HLA-DR/ICOS/CD45RO and exhibit a higher level of IFN-γ, TNF-α, and PD-1 upon stimulation. The enrichment of DPT and PD-1⁺DPT in L regions indicates favorable prognosis. These tumor-associated DPT cells with similar phenotype are also verified in other tumors and HCC animal models. Single-cell RNA-seq further characterizes the molecular features of DPT cells and uncovers 11 clusters

SUBMITTER: Zheng B 

PROVIDER: S-EPMC7341083 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature