Cell Stem Cell: Suppress cancer from the root: Academician Wang Cunyu's team confirmed that blocking CD276 can eliminate cancer stem cells

Cancer Stem Cells are considered the original source of cancer tissues.

When the immune system is functioning normally, the body's natural T cells that fight infection help recognize and defend against cancer cells, foreign viruses, and other invaders.

In order to help T cells get rid of this restriction, scientists have developed "immune checkpoint inhibitors" represented by PD-1/PD-L1 inhibitors, which block immune checkpoints so that T cells can work normally.

On May 3, 2021, the team of Academician Wang Cunyu of the University of California, Los Angeles published a research paper titled: CD276 expression enables squamous cell carcinoma stem cells to evade immune surveillance in the Cell Stem Cell journal .

The study found that CD276 is highly expressed on the surface of head and neck squamous cell carcinoma, as an immune checkpoint that allows cancer stem cells to evade immune system surveillance.

These findings indicate that CD276 can serve as a unique potential target for immunotherapy of head and neck squamous cell carcinoma.

First, the research team tested the anti-PD-1 antibody on a mouse model of head and neck squamous cell carcinoma and found that it had little effect on slowing the spread of cancer cells.

At the same time, they found that the CD276 gene expression of cancer stem cells in head and neck tumors was significantly increased.

Similar to the use of immune checkpoint inhibitors, the research team injected anti-CD276 antibodies into mouse models of head and neck squamous cell carcinoma to see whether this treatment can block immune checkpoints and inhibit the growth and spread of cancer.

In order to provide a more comprehensive and fair assessment of the tumor response after anti-CD276 antibody treatment, the research team conducted single-cell RNA sequencing (scRNA-seq).

Next, in order to prove that CD276 blockade works through the tumor immune microenvironment, the research team performed immune deprivation therapy on mice, which consumes T cells.

The research team once again confirmed the conclusions drawn from animal experiments from human head and neck squamous cell carcinoma samples, that the high expression of CD276 in cancer cells is negatively correlated with T lymphocyte infiltration, but positively correlated with poor prognosis.

In summary, Wang Cunyu’s team used a mouse model of human head and neck squamous cell carcinoma combined with in vivo lineage tracking of cancer stem cells, and confirmed that CD276 is highly expressed in cancer stem cells as an immune checkpoint, and CD276 inhibitors can enhance T cell mediation.

Corresponding author profile

Wang Cunyu , born on August 23, 1963 in Xinghua City, Jiangsu Province, is an academician of the National Academy of Medicine, a foreign academician of the Chinese Academy of Engineering, a chair professor of the School of Dentistry at the University of California, Los Angeles, chair of the Department of Oral Biology and Medicine, and deputy dean.

Wang Cunyu graduated from the Department of Dentistry, Nanjing Medical University in 1985; received a doctorate in clinical medicine from Beijing Medical University in 1989; went to the Forsyth Institute in the United States for postdoctoral research in 1990; received a doctorate from the University of North Carolina in 1998; established himself at the University of Michigan in 1999 Independent laboratory; transferred to the University of California, Los Angeles in 2007, successively served as dean of the Department of Oral Biology and Medicine, chair professor and professor of the Department of Bioengineering of the School of Engineering; elected as a member of the National Academy of Medicine in 2011; elected as a foreign academician of the Chinese Academy of Engineering in 2013 .

Original source:

Cheng Wang, et al.