Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
- MeSH
- imunogenní buněčná smrt genetika MeSH
- konsensus MeSH
- lidé MeSH
- molekulární biologie metody MeSH
- směrnice jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by cells succumbing to immunogenic cell death (ICD) favors the establishment of a productive interface with the immune system. This results in the elicitation of tumor-targeting immune responses associated with the elimination of residual, treatment-resistant cancer cells, as well as with the establishment of immunological memory. Although ICD has been characterized with increased precision since its discovery, several questions remain to be addressed. Here, we summarize and tabulate the main molecular, immunological, preclinical, and clinical aspects of ICD, in an attempt to capture the essence of this phenomenon, and identify future challenges for this rapidly expanding field of investigation.
- Publikační typ
- časopisecké články MeSH
It is now clear that human neoplasms form, progress, and respond to therapy in the context of an intimate crosstalk with the host immune system. In particular, accumulating evidence demonstrates that the efficacy of most, if not all, chemo- and radiotherapeutic agents commonly employed in the clinic critically depends on the (re)activation of tumor-targeting immune responses. One of the mechanisms whereby conventional chemotherapeutics, targeted anticancer agents, and radiotherapy can provoke a therapeutically relevant, adaptive immune response against malignant cells is commonly known as "immunogenic cell death." Importantly, dying cancer cells are perceived as immunogenic only when they emit a set of immunostimulatory signals upon the activation of intracellular stress response pathways. The emission of these signals, which are generally referred to as "damage-associated molecular patterns" (DAMPs), may therefore predict whether patients will respond to chemotherapy or not, at least in some settings. Here, we review clinical data indicating that DAMPs and DAMP-associated stress responses might have prognostic or predictive value for cancer patients.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH