Disease-specific exhaustion features and PD-1 immunotherapy responsiveness of antigen-specific CD8+ T cells at single-cell resolution [scRNA-seq]

We reported the CD8+ T cell exhaustion differences between chronic viral infection and tumor regarding their transcriptomic and epigenetic landscapes, immune checkpoint blockade responsiveness and underlying molecular mechanisms by using bulk RNA-seq, single-cell RNA-seq and single-cell ATAC-seq. Exhausted P14 CD8+ T cells bearing a same TCR recognizing a same epitope presented in either chronic viral infection (LCMV-Cl13) or tumor (B16F10-GP) were harvested and performed with RNA- and ATAC-sequencing. Exhausted P14 CD8+ T cells were obtained from the spleens or lungs of chronic virus-infected mice and from the subcutaneous tumor tissues or metastatic lungs of tumor-engrafted mice. The chronic virus-infected or tumor-engrafted mice were treated with either anti-PD-L1 antibody or isotype antibody. As control, P14 CD8+ T cells from the spleens of acute virus-infected mice were also performed with RNA-sequencing.