immunescape

Immunescape is the process by which pathogens, tumors, or other targets evade detection or elimination by the immune system. It results from genetic or epigenetic changes that reduce immunogenicity or interfere with immune effector functions, allowing continued survival and replication in the host.

Mechanisms include antigenic variation and epitope masking, where surface proteins change or are shielded by glycosylation; downregulation or loss of MHC class I molecules or antigen-presenting machinery, limiting T cell recognition; interference with costimulatory signals or cytokine pathways; upregulation of immune-inhibitory ligands such as PD-L1; and the creation of an immunosuppressive microenvironment by regulatory cells and suppressive cytokines.

In pathogens, immune escape is driven by rapid mutation in RNA viruses, antigenic drift, and selection under immune pressure. In cancer, immune escape arises through somatic mutations, loss of neoantigens, altered antigen presentation, and secretion of immunosuppressive factors. Both contexts show selective pressure favoring variants less visible to immune surveillance.

Clinical relevance: immune escape complicates vaccines and antiviral therapies, and is a major obstacle in cancer immunotherapy. Approaches to counteract include vaccines targeting conserved or multiple epitopes, therapies that enhance antigen presentation, checkpoint inhibitors to release T cell activity, adoptive cell therapies, and combination regimens.

See also: antigenic drift, antigenic shift, immune surveillance, immunoediting.