Pathology

Immunotherapy

Immunogenic cell death

Antigenicity

Disease

Immunogenicity

Biology

Cancer

Antigen

Apoptosis

Acquired immune system

Immunology

Immunosurveillance

Adjuvant

Programmed cell death

Genetics

Medicine

Immune system

Cancer cell

Nature reviews. Immunology

Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process? Immunogenicity depends on two key factors: antigenicity and adjuvanticity. The presence of exogenous or mutated antigens explains why infected cells and malignant cells can initiate an adaptive immune response provided that the cells also emit adjuvant signals as a consequence of cellular stress and death. Several infectious pathogens have devised strategies to control cell death and limit the emission of danger signals from dying cells, thereby avoiding immune recognition. Similarly, cancer cells often escape immunosurveillance owing to defects in the molecular machinery that underlies the release of endogenous adjuvants. Here, we review current knowledge on the mechanisms that underlie the activation of immune responses against dying cells and their pathophysiological relevance.

Immunogenic cell death in cancer and infectious disease