What are MHC Molecules?
Major histocompatibility complex (
MHC) molecules are proteins found on the surface of cells that play a crucial role in the immune system. They help in the presentation of peptide antigens to T cells, facilitating the recognition and destruction of infected or aberrant cells, such as
cancer cells.
Types of MHC Molecules
There are two main classes of MHC molecules:
MHC Class I and
MHC Class II. MHC Class I molecules are expressed on almost all nucleated cells and present endogenous peptides to CD8+
cytotoxic T cells. MHC Class II molecules are primarily expressed on antigen-presenting cells (APCs) like dendritic cells, macrophages, and B cells, presenting exogenous peptides to CD4+
helper T cells.
MHC Downregulation in Cancer
One of the common mechanisms by which cancer cells evade immune surveillance is through the downregulation or loss of MHC molecules on their surface. This can occur via genetic mutations, epigenetic modifications, or alterations in the antigen-processing machinery. The loss of MHC expression impairs the ability of the immune system to recognize and destroy cancer cells.Implications for Immunotherapy
The expression of MHC molecules on cancer cells has significant implications for
immunotherapy. For example, therapies like
checkpoint inhibitors rely on the presence of MHC molecules to effectively activate T cells. Tumors with low or absent MHC expression may be less responsive to these therapies. Strategies to enhance MHC expression or bypass the need for MHC, such as CAR-T cells and
bispecific T-cell engagers (BiTEs), are being developed to overcome this challenge.
Biomarkers and Prognostic Value
The level of MHC expression on tumor cells can serve as a biomarker for prognosis and treatment response. Tumors with high MHC expression generally have better outcomes and are more responsive to immunotherapies. Conversely, low MHC expression is often associated with poor prognosis and resistance to treatment.Future Directions
Research is ongoing to better understand the regulation of MHC molecules in cancer and to develop new strategies to enhance their expression. Approaches like epigenetic drugs, cytokine therapies, and genetic engineering are being explored to boost MHC levels on tumor cells, thereby improving the efficacy of
cancer immunotherapies.
