Immunogenic cell death in cancer and infectious disease

  title={Immunogenic cell death in cancer and infectious disease},
  author={Lorenzo Galluzzi and Aitziber Buqu{\'e} and Oliver Kepp and Laurence Zitvogel and Guido Kroemer},
  journal={Nature Reviews Immunology},
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… 

Immunogenic cell stress and death.

Intriguingly, normal cells succumbing to conditions that promote the formation of post-translational neoantigens can also drive at least some degree of antigen-specific immunity, pointing to a novel implication of ICD in the etiology of non-infectious, non-malignant disorders linked to autoreactivity.

Tumor-intrinsic determinants of immunogenic cell death modalities

How tumor intrinsic oncogenic factors subvert desirable intratumoral inflammation by suppressing immunogenic cell death is discussed.

Immunogenic Stress and Death of Cancer Cells in Natural and Therapy-Induced Immunosurveillance

DAMPs, such as annexin A1, ATP, calreticulin, HMGB1, and type-1 interferons, which are exposed or released from stressed and dying cancer cells in response to ICD inducers and the signal transduction pathways leading to their activation are discussed.

Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy

An otherwise poorly understood role for epigenetic drugs as ICD inducers is put forward, and potential therapeutic innovations that aim to induce ICD during epigenetic drug therapy are discussed, generating highly efficacious cancer immunotherapies.

Immunosuppressive cell death in cancer

Given that various therapeutic strategies suffer clinical failure or resistance, appropriate animal models or clinical validation are needed to re-examine the immuno logical consequences described above, and there are several lines of evidence that conflict with this Review.

Immunogenic Cell Death Driven by Radiation-Impact on the Tumor Microenvironment.

The mechanisms whereby damage-associated molecular patterns emitted by cancer cells undergoing RT-driven ICD alter the functional configuration of the tumor microenvironment are discussed.

Methods to Detect Immunogenic Cell Death In Vivo.

Two methods are described that can be harnessed to straightforwardly determine the immunogenicity of mouse cancer cells succumbing to stress in both tumor-naïve and tumor-bearing hosts.

Immunosurveillance of cancer cell stress

How distinct situations of cellular stress influence innate and adaptive immunity and the consequent impact on cancer establishment and progression is explored.



Immunogenic cell death in cancer therapy.

It is postulate that ICD constitutes a prominent pathway for the activation of the immune system against cancer, which in turn determines the long-term success of anticancer therapies and its subversion by pathogens.

Immunogenic cell death and DAMPs in cancer therapy

The role of endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in regulating the immunogenicity of dying cancer cells and the effect of therapy-resistant cancer microevolution on ICD are discussed.

Consensus guidelines for the detection of immunogenic cell death

Strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative I CD inducers are outlined, based on a high-content, high-throughput platform that was recently developed.

Apoptotic cell clearance: basic biology and therapeutic potential

The current understanding of the complex process of apoptotic cell clearance in physiology and pathology is reviewed, and how this knowledge could be harnessed for new therapeutic strategies are discussed.

Viral subversion of immunogenic cell death

It is postulate that obligate intracellular pathogens have developed a variety of strategies to subvert CRT exposure, thereby avoiding immunogenic cell death.

Inducers of immunogenic cancer cell death.

Calreticulin exposure dictates the immunogenicity of cancer cell death

It is shown that anthracyclin-induced CRT translocation induces the rapid, preapoptotic translocation of calreticulin (CRT) to the cell surface and is identified as a key feature determining anticancer immune responses.

Neoantigens in cancer immunotherapy

Observations indicate that neoantigen load may form a biomarker in cancer immunotherapy and provide an incentive for the development of novel therapeutic approaches that selectively enhance T cell reactivity against this class of antigens.

Viral Control of Mitochondrial Apoptosis

The current knowledge on the viral modulation of mitochondrial apoptosis is summarized, by focusing in particular on the mechanisms by which viral proteins control the host cell death apparatus.