Cancer Escape From T-cells
In order for conventional alpha beta T-cells to recognize and kill a cancer cell, the cancer cell must be presenting mutated protein fragments from inside of the cell to the T-cells on the outside. These protein fragments are presented by classical MHC I molecules. Cancer cells can escape T-cell detection when they stop expressing classical MHC I molecules on their cell surfaces.
Natural Killer Cell Detection of Cancer
Natural Killer cells are designed to detect the loss of classical MHC I on cell surfaces and will kill these cells without classical MHC I unless they are inhibited in another way.
Essentially, Natural Killer cells can take up the slack when the T-cells can no longer "see" the cancer cells.
The Most Dangerous Scenario: When Neither T-cells Nor NK Cells Can Destroy Cancer
Natural Killer cells can be inhibited from attacking cancer when the cancer cells upregulate non-classical MHC I on their surface.
If the non-classical MHC I is upregulated and the classical MHC I is also simultaneously downregulated on cancer cells, neither T-cells nor Natural Killer cells will be able to attack the cancer.
What Are The Solutions?
Increasing the presence of an immune system signaling molecule called Interferon gamma can push cancer cells to express classical MHC I and make them more visible to T-cells.
A challenge arises when mutations in the genes that control MHC presentation machinery prevent MHC expression even in the presence of Interferon gamma. When this is the case, there are new clinical trials to block non-classical MHC I, to give Natural Killer cells a better chance to kill the cancer.
In addition to Natural Killer cells, CAR-T cells which are designed to function in the absence of MHC I may be a solution to MHC loss. Finally, harnessing a more rare type of T-cell called gamma delta T-cells may prove a solution for loss of MHC l expression, but much more research is needed on gamma delta T-cells.