The immune micro-environment and tumor immune escape mechanism of early recurrence of liver cancer were solved

Fudan University (Zhongshan Hospital) Liver Cancer Research Institute, in collaboration with the Shenzhen Huada Institute of Life Sciences, using single-cell RNA sequencing technology, from the single-cell level revealed the early recurrence of liver cancer immune characteristics and tumor immune escape mechanism. The important findings were published online December 23 in Cell.
primary liver cancer (referred to as liver cancer) is a high incidence of malignant tumors in China, with more than half of the new cases detected each year, and the fatality rate remains high, making it a leading spot in clinical cancer research. Relapsed liver cancer, in the five years after liver cancer surgery incidence as high as 60% to 70%, of which 2/3 is in the 2 years after surgery recurrence (early recurrence), become a key factor affecting the patient's prognosis, but also difficult in clinical research. Exploring the mechanisms associated with postoperative recurrence and metastasis of liver cancer can help to identify new strategies for more effective treatment of liver cancer.
study reveals for the first time that there are significant differences in the immune micro-ecosystem between primary and early recurrence tumors of liver cancer. Within the early recurrence of liver cancer, the number of degenerative cells (DC) responsible for immune identification and CD8
T cells responsible for immune attack is greater, while the number of regulatory T-cells that play an immunosuppressive role is smaller, suggesting that the immune escape mechanism for early recurrence of liver cancer is different from that of liver cancer primary tumors. The CD8
T cell characteristic expression KLRB1 (CD161) gene, which is immersed in early recurrence tumors, has an inherent immune sample, low cytotoxicity, and low clone amplification esoteric. The inactivated state of
CD161
CD8
T cells leads to the failure of immunology and lethality, which is one of the important reasons for the early recurrence of liver cancer after surgery. The increase in CD161 and CD8
in
tumors was significantly associated with poor postoperative prognosis. At the same time, tumor cells in early recurrence tumors raised the immune checkpoint molecule PD-L1. The analysis of the compound subject interoperability showed that the correlation between PD-L1 and CD80 molecules of DC was most significant. Since the affinity of the PD-L1 binding to the DC surface CD80 is higher than the affinity of the CD8
T cell surface CD28 molecule binding to the DC surface CD80, i.e. when both PD-L1 and CD28 are present, the CD80 will be preferred to bind to the PD-L1. This causes the DC's costulation signal to CD8
T cells to be competitively suppressed, which in turn blocks the antigen delivery process and inhibits the
of CD8
T cells. Academician Yu Jia made an image analogy, so that the original implementation of education CD8
T cell tumor killing function of DC is relapsed tumor cells blackened, resulting in it can not be effectively activated to perform the function of killing.The study analyzed the immuno-micro-ecological differences between primary and relapsed liver cancers from single-celled horizontal systems, revealed the characteristic immune map and immune escape mechanism of early recurrence of liver cancer, and provided more theoretical basis and experimental evidence for further improving the efficacy of liver cancer immunotherapy and finding effective new strategies for the prevention and treatment of recurrence and metastasis of liver cancer,
said. (Source: Huang Xin, China Science Daily)