In the period of infection or tumor growth, a special white blood cell named CD8+T rapidly reproduces in spleen and lymph node, and obtains the ability to kill normal cells of diseased patients. Then these "killers" fully equip themselves for the place where they are needed.
If we can find evidence to prove how the killers leave the camp on their own initiative and remain voluntarily on the spot of anti-infection/cancer area, it can provide important clues for anti-cancer immunotherapy. However, it is a great challenge to understand this process.
Nature magazine published the a latest article to show that Runx3 acts on the chromatin of killer T cells and directs gene expression to make T cells stay "voluntarily" in solid tumors.
Cancer immunotherapy based on killer T cells to fight cancer is mainly divided into two strategies: one is that the checkpoint inhibitor relieves T cells inhibition, promoting them to attack more aggressive tumors positively; the other one is the adoptive cell immune by designing and transforming autoimmune cells in vitro, making them recognize and kill cancer specifically, and then injecting them into the patient.
Adoptive cell immunization strategy often has good curative effect on leukemia and lymphatic system, but is not effective on solid tumor.
"This is because we almost absolutely have no idea of gene program and signal pathway which make T cells reside in tissues beyond non-circulation system.” Matthew Pipkin, an immunology and microbiology professor on Florida campus of Scripps Research Institute, said.
To find out the key factor that T cells could reside outside the lymphatic system, the Pipkin team worked with the Ananda Goldrath team at the San Diego branch of University of California, comparing the gene expression of CD8 T cells from circulatory system to non-lymphoid tissue, and finding a long list of potential regulatory factors.
As a result, they used a high-throughput RNA interference strategy that could screen thousands of factors at the same time.
"We find a significantly different expression pattern," Pipkin said. "Runx3 has the highest score, so it is probably the key factor for T cells to reside in non-lymphoid tissue". 
(Adapted from: Ager. A. et al., Biochem Soc Trans, 2016, Rosenberg, S.A. et al., Science, 2015)
The research team further assessed the effect of Runx3 on leukocyte attacking solid tumors in the melanoma mouse model.
They found that tumor specific killing T cells used for adoptive T cell therapy would delay tumor growth and prolong the survival time of mice if Runx3 was over-expressed. On the contrary, T cells lacking Runx3 showed a worse effect than normal T cells.
"This is a very exciting result—increasing Runx3 cell activity can significantly reduce the tumor size and improve the survival rate," Pipkin said.
This result not only clarifies the key factors affecting the presence of T cells in solid tumor, but also points out the direction of genetic programming for adoptive T cell therapy. That means, adoptive T cell immunotherapy (such as CAR-T) which has shown good effect in the blood and lymph cancer, may soon be able to perform in the field of solid tumor treatment!
Reference:
J. Justin Milner, Clara Toma, Bingfei Yu, et al. Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours. Nature (2017). DOI: 10.1038/nature24993