Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.
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
- MeSH
- autofagie * fyziologie MeSH
- biotest metody normy MeSH
- lidé MeSH
- počítačová simulace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- směrnice 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
Hair follicles are unique organs undergoing regular cycles of proliferation, differentiation, and apoptosis. The final step of apoptosis is, in general, mediated by executioner caspases comprising caspase-3, -6 and -7. Despite their commonly accepted apoptotic function, executioner caspases also participate in non-apoptotic processes. In the present study, we investigated activation (cleavage) of caspase-7 in mouse hair follicles and surrounding tissue during embryonic development into adulthood. Casp7 (-/-) mice were examined to understand the effect of caspase-7 deficiency in the skin. The activated form of caspase-7 was observed during embryonic hair follicle development, as well as in the first hair cycle. In general, activation of caspase-7 did not correlate with apoptosis and activation of caspase-3, except during physiological hair follicle regression. Notably, cleaved caspase-7 was observed in mast cells and its deficiency in the adult skin resulted in increased mast cell number. Our study shows for the first time activated caspase-7 in hair follicles and mast cells and indicates its non-apoptotic roles in the skin.
- MeSH
- aktivace enzymů MeSH
- apoptóza * MeSH
- exprese genu MeSH
- kaspasa 3 metabolismus MeSH
- kaspasa 7 nedostatek genetika metabolismus MeSH
- kaspasy genetika metabolismus MeSH
- kůže embryologie metabolismus MeSH
- mastocyty metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- počet buněk MeSH
- transport proteinů MeSH
- vlasový folikul embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Apoptosis during tooth development appears dependent on the apoptotic executioner caspase-3, but not caspase-7. Instead, activated caspase-7 has been found in differentiated odontoblasts and ameloblasts, where it does not correlate with apoptosis. To further investigate these findings, the mouse incisor was used as a model. Analysis of caspase-7-deficient mice revealed a significant thinner layer of hard tissue in the adult incisor. Micro computed tomography scan confirmed this decrease in mineralized tissues. These data strongly suggest that caspase-7 might be directly involved in functional cell differentiation and regulation of the mineralization of dental matrices.
- MeSH
- ameloblasty cytologie enzymologie metabolismus MeSH
- buněčná diferenciace * MeSH
- časové faktory MeSH
- imunohistochemie MeSH
- kaspasa 7 genetika metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- odontoblasty cytologie enzymologie metabolismus MeSH
- odontogeneze MeSH
- proliferace buněk MeSH
- rentgenová mikrotomografie MeSH
- řezáky embryologie růst a vývoj metabolismus MeSH
- zubní sklovina embryologie růst a vývoj metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
A handheld Raman spectrometer (Ahura First Defender) was tested for the unambiguous identification of biomolecules (pure amino acids, carboxylic acids, saccharides and trehalose) in the solid state under outdoor conditions (including moderate climate conditions as well as cold temperatures and high altitudes). The biomolecules investigated represent important objects of interest for future exobiological missions. Repetitive measurements carried out under identical instrumental setups confirmed the excellent reliability of the Raman spectrometer. Raman bands are found at correct wavenumbers +/-3 cm(-1) compared with reference values. This testing represents the first step in a series of studies. In a preliminary, challenging investigation to determine the detection limit for glycine dispersed in a powdered gypsum matrix, 10% was the lowest content confirmed unambiguously. Clearly there is a need to investigate further the detection limits of Raman spectroscopic analyses of biomolecules in more complex samples, to demonstrate the usefulness or disqualify the use of this technique for more realistic outdoor situations, such as eventual future missions to Mars.
- MeSH
- aminokyseliny analýza MeSH
- exobiologie přístrojové vybavení metody MeSH
- kyseliny karboxylové analýza MeSH
- limita detekce MeSH
- nadmořská výška MeSH
- nízká teplota MeSH
- Ramanova spektroskopie metody MeSH
- sacharidy analýza MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
