Researchers from University of California – San Diego identified a molecular “brake” known as PD-1 can bind and neutralize the same tumor cell, instead of an opposing tumor cell.
Researchers from the University of California (UC) San Diego decoded the unexpected mechanism of immune system that eliminates tumor cells. The study led by Enfu Hui, a post-doctoral research fellow at UC demonstrates whether a cancer patient will respond to immunotherapy. Tumors are recognized as a threat by the immune system and immune cells are deployed to eliminate them. However, these tumor cells employ a protein called PD-L1 that restrict T cells from eliminating then. Hence, PD-L1 help tumor cells to evade the immune response by activating a “molecular brake” known as PD-1 to stop T cells. Earlier therapeutic progresses blocked PD-L1/PD-1 to benefit certain cancer patients. However, the antibodies in the process are not effective in some patients. Now, UC San Diego’s researchers observed that some tumor cells display not only their PD-L1 weapon, but also the PD-1 “brake.” This stimulates PD-1 to bind and neutralize PD-L1 on the same tumor cell, which in turn disables the PD-1 brake on T cells. The researches stated that cases with high levels of PD-1 on tumor cells may not respond well to the blocking antibodies as the PD-1 pathway is self-canceled. The mechanisms other than PD-L1/PD-1 are likely employed by the tumors to escape from immune destruction.
The researchers are focusing to extend the efficiency of immunotherapy by determining additional mechanisms of “self-cancellation” at the interface of the tumor and immune cells that regulates immune cell function. These processes develop better and reliable immunotherapy strategies that can predict whether a patient will respond. The researchers was published in the journal Cell Report on July 10, 2018.