Nejvíce citovaný článek - PubMed ID 28197379
Caspase-2 and oxidative stress underlie the immunogenic potential of high hydrostatic pressure-induced cancer cell death
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.
- Klíčová slova
- immunology, molecular biology, oncology,
- 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 term 'immunogenic cell death' (ICD) denotes an immunologically unique type of regulated cell death that enables, rather than suppresses, T cell-driven immune responses that are specific for antigens derived from the dying cells. The ability of ICD to elicit adaptive immunity heavily relies on the immunogenicity of dying cells, implying that such cells must encode and present antigens not covered by central tolerance (antigenicity), and deliver immunostimulatory molecules such as damage-associated molecular patterns and cytokines (adjuvanticity). Moreover, the host immune system must be equipped to detect the antigenicity and adjuvanticity of dying cells. As cancer (but not normal) cells express several antigens not covered by central tolerance, they can be driven into ICD by some therapeutic agents, including (but not limited to) chemotherapeutics of the anthracycline family, oxaliplatin and bortezomib, as well as radiation therapy. In this Trial Watch, we describe current trends in the preclinical and clinical development of ICD-eliciting chemotherapy as partner for immunotherapy, with a focus on trials assessing efficacy in the context of immunomonitoring.
- Klíčová slova
- Antigen-presenting cell, CAR T cells, autophagy, chemokines, cytokines, cytotoxic T lymphocyte, dendritic cell, endoplasmic reticulum stress, immune checkpoint blocker, type I interferon,
- MeSH
- adaptivní imunita MeSH
- imunogenní buněčná smrt MeSH
- imunoterapie MeSH
- lidé MeSH
- nádory * farmakoterapie MeSH
- protinádorové látky * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- protinádorové látky * MeSH
Dendritic cells (DCs) are key regulators of immune responses that operate at the interface between innate and adaptive immunity, and defects in DC functions contribute to the pathogenesis of a variety of disorders. For instance, cancer evolves in the context of limited DC activity, and some autoimmune diseases are initiated by DC-dependent antigen presentation. Thus, correcting aberrant DC functions stands out as a promising therapeutic paradigm for a variety of diseases, as demonstrated by an abundant preclinical and clinical literature accumulating over the past two decades. However, the therapeutic potential of DC-targeting approaches remains to be fully exploited in the clinic. Here, we discuss the unique features of DCs that underlie the high therapeutic potential of DC-targeting strategies and critically analyze the obstacles that have prevented the full realization of this promising paradigm.
- Klíčová slova
- autoimmune disorders, cancer, dendritic cells, immunotherapy, vaccine preparation,
- MeSH
- antigen prezentující buňky imunologie metabolismus MeSH
- autoimunita MeSH
- autoimunitní nemoci etiologie metabolismus terapie MeSH
- buněčná diferenciace genetika imunologie MeSH
- dendritické buňky imunologie metabolismus MeSH
- imunita * MeSH
- imunologická tolerance * MeSH
- imunoterapie MeSH
- lidé MeSH
- mezibuněčná komunikace MeSH
- náchylnost k nemoci MeSH
- nádory etiologie metabolismus patologie terapie MeSH
- plasticita buňky genetika imunologie MeSH
- prezentace antigenu imunologie MeSH
- protinádorové vakcíny aplikace a dávkování imunologie MeSH
- T-lymfocyty imunologie metabolismus MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- protinádorové vakcíny MeSH