Nearly 20 years ago, Prof. Mark Lowdell began research to better understand the difference between the NK cells of survivors and relapsers. The scientific community assumed the issue was one of immune cell function – a defective NK cell. That is, the NK cells in relapsers did not have the ability to kill the residual cancer cells.
Prof. Lowdell showed that NK cells of survivors and relapsers have an equal ability to kill cancer cells. The difference was the AML cancer cells from survivors prime the resting NK cells, initiating the NK killing mechanism. In contrast, the AML cancer cells in relapsers failed to prime the NK cells and they remained at rest. Without NK-mediated killing, the residual AML cancer cells in relapsers grew and the leukemia returned.
This important observation by Prof. Lowdell led to the discovery that while the killing and targeting ability of survivor and relapse NK cells were the same, the relapsers’ cancer cells had undergone changes to evade NK surveillance. That is the relapsers’ cancer cells were hiding in plain sight! The NK cells could kill the cancer cells if primed, but priming did not occur due to some evolutionary trickery on the part of the cancer cells. So the problem was with the cancer cells, not with the immune system!