Clinical Microbiology: Open Access

Immunogenic cell death in cancer and infectious disease

Joint Event on 17^th International Conference on Pharmaceutical Microbiology and Biotechnology & 23^rd Edition of International Conference on Immunology and Infectious Diseases

April 29-30, 2019 London, UK

Guido Kroemer

University of Paris Descartes, France

Posters & Accepted Abstracts: Clin Microbiol

Abstract:

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. Conventional chemotherapeutics and targeted antineoplastic agents have been developed based on the simplistic notion that cancer constitutes a cell-autonomous genetic or epigenetic disease. Nonetheless, it is becoming clear that many of the available anticancer drugs that have collectively saved millions of life-years mediate therapeutic effects by eliciting de novo or reactivating preexisting tumor-specific immune responses. I will discuss the capacity of anticancer therapies to enhance the immunogenic properties of malignant cells and to stimulate immune effector cells, either directly or by subverting the immunosuppressive circuitries that preclude antitumor immune responses in cancer patients. Accumulating evidence indicates that the therapeutic efficacy of many (if not most) antineoplastic agents relies on their capacity to influence the tumor-host interaction, tipping the balance toward the activation of an immune response specific for malignant cells. One particular way to reinstate immunosurveillance consists in the induction of immunogenic cell death (ICD), which involves elements of organelle-specific, autophagic, apoptotic and necroptotic stress signaling. ICD involves changes in the composition of the cell surface as well as the release of soluble mediators, occurring in a defined temporal sequence. Such signals operate on a series of receptors expressed by dendritic cells to stimulate the presentation of tumor antigens to T cells. We 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. Hence, suboptimal regimens (failing to induce ICD), selective alterations in cancer cells (preventing the emission of immunogenic signals during ICD), or defects in immune effectors (abolishing the perception of ICD by the immune system) can all contribute to therapeutic failure.

Biography :

E-mail: kroemer@orange.fr