癌细胞衰老,癌细胞 z-bo 2020-08-17 507

　　The human adaptive immune system plays an important role in the control of cancer and has been widely recognized. People have been working on developing effective targeted cancer immunotherapy. Many of these treatment methods do not eliminate cancer cells through cytotoxicity, but instead inhibit the growth of cancer cells.

　　Martin from the University of Tubingen, Germany? Under the leadership of a research team, Cken discovered a new type of TH1 cell that can stop the growth of cancer cells and clarified the molecular mechanism of these cells in a new study. Related papers were published in Nature on February 3.

　　cken et al. conducted an experimental study using a transgenic mouse model. The mouse model tumor antigen tag is expressed under the control of the rat insulin promoter, and causes invasive β-cell carcinoma by partially or completely silencing the tumor suppressor p53 and Rb. The researchers found that only CD4 + TH1 cells that secrete TNF and IFN-g can inhibit the growth of these tumors. This will double the life of the mouse. The researchers found that mouse tumor cells treated with sham surgery can continue to grow, while mouse tumor cells treated with TH1 cells cannot grow in vitro. Next, the researchers co-cultured β cancer cells from mice in the sham treatment group with TNF, IFN-g or a control medium. Three days later, the cytokine-treated cells stagnated in the G1/G0 phase of the cell cycle. I found that on the contrary, more than 25% of cells that have not been treated with these cytokines enter the S phase, indicating that they are proliferating at a high rate. As we all know, G1/G0 tumor cell arrest is a sign of cell senescence. Therefore, the researchers further investigated whether the cytokines IFN-g and TNF can cause long-term tumor senescence and growth arrest. They washed the cells treated with cytokines for 5 days and then cultured them for another 2 weeks. The researchers found that these cells can fully age for two weeks, while cells that have not been treated with cytokines grow rapidly during this period. In these cytokine-treated cells, the researchers also observed changes in gene expression patterns and epigenetics that are known to be associated with cellular senescence. Researchers observed the expression of early senescence marker genes (such as pHP1c) after treatment with IFN-g and TNF for 3 days. After 4 days of cytokine incubation, the expression of senescence-related b-galactosidase (SA-b-gal) and other late senescence genes and stable growth arrest were observed. Treatment with IFN-g or TNF alone may cause some related changes in gene expression, but it is not enough to cause long-term growth arrest. In addition, the researchers found that the transcription factor STAT1 and TNF receptor TNFR1 (also known as CD120) activate the p16INK4a target protein downstream of JUNB. This signal transduction is a necessary condition for cytokines that induce senescence. In addition, the researchers found that IFN-g and TNF induce the expression of p16INK4a and promote the phosphorylation of the tumor suppressor protein RbSer795. This series of changes induced the senescence of β cancer cells by stabilizing the p16INK4a–Rb signal. Researchers have confirmed that beta cancer cells lacking STAT1 or TNFR1 will not enter a state of senescence after being given IFN-g and TNF. Researchers have also observed this cytokine-induced senescence in several other mouse and human cell lines, as well as in spontaneously regressing human melanoma cells. This result may play a role in tumor immunology. Has a broad meaning. For testing

　　Can TH1 cytokines induce tumor senescence in vivo, R? Ken et al transplanted different β cancer cell lines into immunodeficient mice. We found that in mice treated with Tag-TH1 cells, β cancer cells could not grow after transplantation, and similar cells that did not express TNFR1 actively grew in mice. These results indicate that IFN-g and TNF secreted by TH1 cells drive the senescence mechanism of tumor cells through the p16INK4a-Rb signaling pathway, and are tumor-specific in some types of tumors. The reason for the clinical effect of treatments that stimulate TH1 immunity.