Nejvíce citovaný článek - PubMed ID 36840906
Over the course of the last 10 years, clinical oncology has seen significant changes. Although there has been much interest in targeting cancer cells with immunotherapy, the initial enthusiasm has waned as clinical trial results have not met the initial expectations, especially for solid tumors. As a result, research efforts are now shifting towards the study of other cells in the tumor microenvironment. Cancer‑associated fibroblasts (CAFs) are one of the main adversarial cell types that help cancer cells to resist oncological treatment. However, although CAFs have been extensively studied in different types of carcinomas, their role in sarcomas remains poorly understood. Despite this topic being of especial importance, to the best of the authors' knowledge, no literature review currently addresses and summarizes the up‑to‑date knowledge on the role of CAFs in sarcomas. The present review article aimed to address this literature gap by summarizing our current understanding of CAFs in carcinomas and integrating this information with what is currently known about CAFs in sarcomas. The review also suggested novel approaches for targeting CAFs, and outlines new avenues for identifying novel therapeutic targets, which may markedly impact future research in this field.
- Klíčová slova
- cancer‑associated fibroblasts, carcinoma, human malignancies, sarcoma,
- MeSH
- fibroblasty asociované s nádorem * patologie imunologie účinky léků metabolismus MeSH
- lidé MeSH
- nádorové mikroprostředí imunologie účinky léků MeSH
- sarkom * patologie imunologie farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy 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