Nejvíce citovaný článek - PubMed ID 33182777
Single-Cell RNA Sequencing Unravels Heterogeneity of the Stromal Niche in Cutaneous Melanoma Heterogeneous Spheroids
Wound healing represents a complex and evolutionarily conserved process across vertebrates, encompassing a series of life-rescuing events. The healing process runs in three main phases: inflammation, proliferation, and maturation/remodelling. While acute inflammation is indispensable for cleansing the wound, removing infection, and eliminating dead tissue characterised by the prevalence of neutrophils, the proliferation phase is characterised by transition into the inflammatory cell profile, shifting towards the prevalence of macrophages. The proliferation phase involves development of granulation tissue, comprising fibroblasts, activated myofibroblasts, and inflammatory and endothelial cells. Communication among these cellular components occurs through intercellular contacts, extracellular matrix secretion, as well as paracrine production of bioactive factors and proteolytic enzymes. The proliferation phase of healing is intricately regulated by inflammation, particularly interleukin-6. Prolonged inflammation results in dysregulations during the granulation tissue formation and may lead to the development of chronic wounds or hypertrophic/keloid scars. Notably, pathological processes such as autoimmune chronic inflammation, organ fibrosis, the tumour microenvironment, and impaired repair following viral infections notably share morphological and functional similarities with granulation tissue. Consequently, wound healing emerges as a prototype for understanding these diverse pathological processes. The prospect of gaining a comprehensive understanding of wound healing holds the potential to furnish fundamental insights into modulation of the intricate dialogue between cancer cells and non-cancer cells within the cancer ecosystem. This knowledge may pave the way for innovative approaches to cancer diagnostics, disease monitoring, and anticancer therapy.
- Klíčová slova
- IL-6, cancer-associated fibroblasts, granulation tissue, myofibroblasts, wound healing,
- MeSH
- autoimunita * MeSH
- hojení ran * imunologie MeSH
- interleukin-6 * metabolismus imunologie MeSH
- lidé MeSH
- nádorové mikroprostředí * imunologie MeSH
- nádory * imunologie metabolismus patologie MeSH
- stárnutí * imunologie MeSH
- zánět * imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- interleukin-6 * MeSH
Soft tissue sarcomas are aggressive mesenchymal-origin malignancies. Undifferentiated pleomorphic sarcoma (UPS) belongs to the aggressive, high-grade, and least characterized sarcoma subtype, affecting multiple tissues and metastasizing to many organs. The treatment of localized UPS includes surgery in combination with radiation therapy. Metastatic forms are treated with chemotherapy. Immunotherapy is a promising treatment modality for many cancers. However, the development of immunotherapy for UPS is limited due to its heterogeneity, antigenic landscape variation, lower infiltration with immune cells, and a limited number of established patient-derived UPS cell lines for preclinical research. In this study, we established and characterized a novel patient-derived UPS cell line, JBT19. The JBT19 cells express PD-L1 and collagen, a ligand of the immune checkpoint molecule LAIR-1. JBT19 cells can form spheroids in vitro and solid tumors in immunodeficient nude mice. We found JBT19 cells induce expansion of JBT19-reactive autologous and allogeneic NK, T, and NKT-like cells, and the reactivity of the expanded cells was associated with cytotoxic impact on JBT19 cells. The PD-1 and LAIR-1 ligand-expressing JBT19 cells show ex vivo immunogenicity and effective in vivo xenoengraftment properties that can offer a unique resource in the preclinical research developing novel immunotherapeutic interventions in the treatment of UPS.
- MeSH
- antigeny CD274 metabolismus MeSH
- buněčné linie MeSH
- imunoterapie MeSH
- lidé MeSH
- ligandy MeSH
- maligní fibrózní histiocytom * MeSH
- myši nahé MeSH
- myši MeSH
- sarkom * patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD274 MeSH
- ligandy MeSH
The incidence of cutaneous malignant melanoma is increasing worldwide. While the treatment of initial stages of the disease is simple, the advanced disease frequently remains fatal despite novel therapeutic options . This requires identification of novel therapeutic targets in melanoma. Similarly to other types of tumours, the cancer microenvironment plays a prominent role and determines the biological properties of melanoma. Importantly, melanoma cell-produced exosomes represent an important tool of intercellular communication within this cancer ecosystem. We have focused on potential differences in the activity of exosomes produced by melanoma cells towards melanoma-associated fibroblasts and normal dermal fibroblasts. Cancer-associated fibroblasts were activated by the melanoma cell-produced exosomes significantly more than their normal counterparts, as assessed by increased transcription of genes for inflammation-supporting cytokines and chemokines, namely IL-6 or IL-8. We have observed that the response is dependent on the duration of the stimulus via exosomes and also on the quantity of exosomes. Our study demonstrates that melanoma-produced exosomes significantly stimulate the tumour-promoting proinflammatory activity of cancer-associated fibroblasts. This may represent a potential new target of oncologic therapy .
- Klíčová slova
- Cancer-associated fibroblasts, Exosomes, IL-6, IL-8, Melanoma, Proinflammatory cytokine,
- MeSH
- exozómy metabolismus MeSH
- fibroblasty metabolismus patologie MeSH
- lidé MeSH
- melanom experimentální metabolismus patologie MeSH
- nádorové buňky kultivované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cancer-associated fibroblasts (CAFs) are an essential component of the tumour microenvironment. They represent a heterogeneous group of cells that are under the control of cancer cells and can reversely influence the cancer cell population. They affect the cancer cell differentiation status, and the migration and formation of metastases. This is achieved through the production of the extracellular matrix and numerous bioactive factors. IL-6 seems to play the central role in the communication of noncancerous and cancer cells in the tumour. This review outlines the role of exosomes in cancer cells and cancer-associated fibroblasts. Available data on the exosomal cargo, which can significantly intensify interactions in the tumour, are summarised. The role of exosomes as mediators of the dialogue between cancer cells and cancer-associated fibroblasts is discussed together with their therapeutic relevance. The functional unity of the paracrine- and exosome-mediated communication of cancer cells with the tumour microenvironment represented by CAFs is worthy of attention.
- Klíčová slova
- IL-6, cancer ecosystem, cancer microenvironment, cancer-associated fibroblast, exosome,
- MeSH
- exozómy metabolismus MeSH
- fibroblasty asociované s nádorem metabolismus MeSH
- interleukin-6 metabolismus MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory metabolismus MeSH
- parakrinní signalizace MeSH
- pohyb buněk MeSH
- proliferace buněk MeSH
- regulace genové exprese u nádorů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- IL6 protein, human MeSH Prohlížeč
- interleukin-6 MeSH
Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.
- Klíčová slova
- IL-6, cancer microenvironment, head and neck cancer, targeted therapy,
- MeSH
- interleukin-6 imunologie metabolismus MeSH
- lidé MeSH
- nádorové mikroprostředí * MeSH
- nádory hlavy a krku imunologie terapie MeSH
- signální transdukce MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- interleukin-6 MeSH
COVID-19 is a transmissible respiratory disease caused by coronavirus SARS-CoV-2, which is similar to SARS or MERS. Its increased severity was noted in aged patients usually over 65 years of age. Children and young people have an asymptomatic or mild course of the disease.Unfortunately, the number of children with problems after mild or asymptomatic COVID-19 recovery is increasing and their troubles resemble Kawasaki disease, although the laboratory findings seem to be different. This condition is called pediatric inflammatory multisystem syndrome (PIMS), and it is a new disease seen in children directly influenced by previous SARS-CoV-2 infection. The literature reports that PIMS typically follows 2-4 weeks after SARS-CoV-2 infection. The clinical symptoms of the affected children are extremely complex, ranging from gastrointestinal to cardiovascular problems with frequent skin and mucosal manifestations, and without intensive treatment they can be fatal. The exact causes of PIMS are recently unknown, however, it is explained as hyperactivation of immunity.In this minireview, we summarize data on the prominent role of the IL-6-IL-6R-STAT3 axis in PIMS aetiopathogenesis. Therapeutic manipulation of IL-6 or IL-6 receptor could be an approach to the treatment of children with severe PIMS.
- MeSH
- COVID-19 komplikace etiologie patofyziologie MeSH
- cytokiny * MeSH
- dítě MeSH
- interleukin-6 * MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- syndrom systémové zánětlivé reakce etiologie patofyziologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cytokiny * MeSH
- IL6 protein, human MeSH Prohlížeč
- interleukin-6 * MeSH