One of the fundamental ways cancer escapes immune system detection is by:
both downregulating expression of
CLASSICAL MHC I molecules (HLA-ABC)
and upregulating expression of
NON-CLASSICAL MHC I molecules (HLA-EG).
Currently, MHC I analysis of tumors is not part of clinical practice but this crucial piece of information could help oncologists develop more precise treatment plans and select the most optimal of clinical trial options for their patients.
Almost every single cell of your body expresses MHC I.
MHC I presents protein fragments from inside of your cells to the outside where immune system cells are patrolling. If a mutated protein fragment is detected by a T-cell, the T-cell may destroy the cell.
T-cell surveillance is one of the ways your immune system can distinguish "self" from "non-self" and it is why when people receive donated bone marrow or organs, they first have to be MHC matched to a donor.
The level of MHC I expression in tumors can be tested using antibodies that attach to MHC molecules. This type of test is called IHC (immunohistochemistry).
The difficulty with MHC I expression testing comes stems from the fact that MHC I genes are some of the most varied in all of the human genome and each person has six classical MHC I genes.
Therefore, to assure accuracy of the selected antibodies for IHC staining, it is necessary we invest in validation testing across a wider range of MHC I phenotypes.