Brain tumor is one of the most aggressive cancer that is hard to eliminate. Korean researchers at Korean Advanced Institute of Science and Technology (KAIST) report the discovery of mechanism underlying immune cell-tumor cell cross-talk. The study appears in the journal Nature Immunology in February.

Unlike to other tumors, brain tumor progression was not dependent on conventional T cell infiltration. γδ T cells, which is a type of innate T cells, were related with positive prognosis for brain tumors.

The researchers found that excessive oxygen consumption of tumor cells suppressed γδ T cells through hypoxia. Metformin, which is known to drug for type II diabetes, treatment inhibited respiration of brain tumor cells. In results, γδ T cells were able to use normal concentration of oxygen and reinvigorated to kill brain tumor cells. Oxygen consumption of γδ T cells increased surface expression of tumor cell sensor, NKG2D. The researchers showed that combination therapy using metformin and γδ T cell therapy dramatically increased survival rate of tumor-bearing mice.

Prof. Lee said that “We showed for the first time the principle how brain tumor cells and γδ T cells interact”. “Because clinical trials of current immunotherapy were failed for brain tumors, innovative strategy has been needed. We expect that our findings will provide a insight to develop effective anticancer therapy”, Prof. Lee said.

[Reference] Park J.H. et al., (2021) “Tumor hypoxia represses γδ T cell-mediated antitumor immunity against brain tumors” Nature Immunology

[Main Author] Jang Hyun Park (Korea Advanced Institute of Science and Technology) 

* Contact : Proffessor Heung Kyu Lee (heungkyu.lee@kaist.ac.kr)