The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma

Li, Z., Zheng, B., Qiu, X.

Immunotherapy is a powerful therapeutic strategy for end-stage hepatocellular carcinoma (HCC). It is well known that T cells, including CD8+PD-1+ T cells, play important roles involving tumor development. However, their underlying phenotypic and functional differences of T cell subsets remain unclear. We constructed single-cell immune contexture involving approximate 20,000,000 immune cells from 15 pairs of HCC tumor and non-tumor adjacent tissues and 10 blood samples (including five of HCCs and five of healthy controls) by mass cytometry. scRNA-seq and functional analysis were applied to explore the function of cells. Multi-color fluorescence staining and tissue micro-arrays were used to identify the pathological distribution of CD8+PD-1+CD161 +/− T cells and their potential clinical implication. The differential distribution of CD8+ T cells subgroups was identified in tumor and non-tumor adjacent tissues. The proportion of CD8+PD1+CD161+ T cells was significantly decreased in tumor tissues, whereas the ratio of CD8+PD1+CD161− T cells was much lower in non-tumor adjacent tissues. Diffusion analysis revealed the distinct evolutionary trajectory of CD8+PD1+CD161+ and CD8+PD1+CD161− T cells. scRNA-seq and functional study further revealed the stronger immune activity of CD8+PD1+CD161+ T cells independent of MHC class II molecules expression. Interestingly, a similar change in the ratio of CD8+CD161+/ CD8+CD161− T cells was also found in peripheral blood samples collected from HCC cases, indicating their potential usage clinically. We here identified different distribution, function, and trajectory of CD8+PD-1+CD161+ and CD8+PD-1+CD161− T cells in tumor lesions, which provided new insights for the heterogeneity of immune environment in HCCs and also shed light on the potential target for immunotherapy.


Li, Z., Zheng, B., Qiu, X. "The identification and functional analysis of CD8+PD-1+CD161+ T cells in hepatocellular carcinoma" npj Precision Oncology (2020):