Cancer immune escape: the role of antigen presentation machinery

Abstract

The mechanisms of antigen processing and presentation play a crucial role in the recognition and targeting of cancer cells by the immune system. Cancer cells can evade the immune system by downregulating or losing the expression of the proteins recognized by the immune cells as antigens, creating an immunosuppressive microenvironment, and altering their ability to process and present antigens. This review focuses on the mechanisms of cancer immune evasion with a specific emphasis on the role of antigen presentation machinery. The study of the immunopeptidome, or peptidomics, has provided insights into the mechanisms of cancer immune evasion and has potential applications in cancer diagnosis and treatment. Additionally, manipulating the epigenetic landscape of cancer cells plays a critical role in suppressing the immune response against cancer. Targeting these mechanisms through the use of HDACis, DNMTis, and combination therapies has the potential to improve the efficacy of cancer immunotherapy. However, further research is needed to fully understand the mechanisms of action and optimal use of these therapies in the clinical setting.

Keywords: Epigenetic modulation; Immunopeptidome; MHC-I; Neoantigens.

Fig. 1

Immune checkpoint inhibitors, such as anti-CTLA-4 and anti-PD-1/PD-L1 drugs, enhance the immune response against cancer by blocking immune checkpoint pathways. Other checkpoint pathways, such as LAG-3 and TIGIT, are being investigated as potential targets for cancer therapy and may have synergistic effects when combined with other checkpoint inhibitors

Fig. 2

APCs internalize cancer cell-associated antigens and degrade them into small peptides, which are then presented on the surface of APCs as MHC-peptide complexes that can be recognized by T cells. Cancer cells can evade the immune system by downregulating or losing the expression of antigen proteins, altering their ability to process and present antigens, or creating an immunosuppressive microenvironment

Fig. 3

MHC-I antigen presentation. MHC-I molecules on the cell surface present intracellular antigen peptides to CD8 + T cells. Cancer cells can evade the immune system by downregulating antigen expression or altering antigen processing and presentation on MHC-I

Fig. 4

Tumors can evade detection and destruction by the immune system, thereby allowing for uncontrolled growth and progression. This process is referred to as immune evasion and is a complex mechanism that involves the downregulation or loss of antigens recognized by immune cells, the creation of an immunosuppressive microenvironment, and interaction with immune checkpoint pathways

Fig. 5

Diagram illustrating the epigenetic regulation of chromatin accessibility and gene expression in cells. Nucleosomes, formed by DNA wrapped around histone octamers, are depicted as blue cylinders. Epigenetic modifications are depicted as dynamic interactions between chromatin components and enzymes, including histone methylation/demethylation, histone acetylation/deacetylation, and DNA methylation. Chromatin remodelling also plays a role in regulating gene expression