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.

• Keywords
• cancer‑associated fibroblasts, carcinoma, human malignancies, sarcoma,
• MeSH
• Cancer-Associated Fibroblasts * pathology   immunology   drug effects   metabolism   MeSH
• Humans MeSH
• Tumor Microenvironment immunology   drug effects   MeSH
• Sarcoma * pathology   immunology   drug therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Acute cellular rejection (ACR) frequently occurs following lung transplantation (LuTx) and represents a risk factor for the development of chronic lung allograft dysfunction (CLAD) as well as long-term survival. The histopathological diagnosis of ACR carries a burden of interobserver variability. The widespread utilization and cost-effectiveness of immunohistochemistry (IHC) was proven beneficial in diagnosing rejection in human kidney transplantations and LuTx rat models. However, its potential for ACR detection in patients remains unexplored. We analyzed surface markers (CD3, CD4, CD8, CD20, CD68, CD47, PD-1, PD-L1, and CD31/PECAM-1) on lung tissue cryobiopsy samples collected within 6 months post-LuTx from 60 LuTx recipients, 48 of whom were diagnosed with ACR. Additionally, serum samples from 51 patients were analyzed using a multiplex bead-based Luminex assay. The cytokines and markers included PD-L1, IL2, TNFα, IFNγ, and Granzyme B. We observed a significant increase in PD-L1 tissue expression within the rejection group, suggesting a concerted effort to suppress immune responses, especially those mediated by T-cells. Furthermore, we noted significant differences in PECAM-1 levels between ACR/non-ACR. Additionally, peripheral blood C-reactive-protein levels tended to be higher in the ACR group, while Luminex serum analyses did not reveal any significant differences between groups. In conclusion, our findings suggest the potential value of PECAM-1 and PD-L1 markers in diagnosing ACR.

• Keywords
• acute cellular rejection, checkpoint inhibitors, immunohistochemistry, luminex, lung transplantation,
• MeSH
• Acute Disease MeSH
• B7-H1 Antigen * metabolism   blood   MeSH
• Platelet Endothelial Cell Adhesion Molecule-1 * metabolism   MeSH
• Biomarkers * blood   metabolism   MeSH
• Adult MeSH
• Immunohistochemistry MeSH
• Middle Aged MeSH
• Humans MeSH
• Lung pathology   MeSH
• Graft Rejection * diagnosis   blood   MeSH
• Aged MeSH
• Lung Transplantation * adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• B7-H1 Antigen * MeSH
• Platelet Endothelial Cell Adhesion Molecule-1 * MeSH
• Biomarkers * MeSH
• CD274 protein, human MeSH Browser
• PECAM1 protein, human MeSH Browser

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
• B7-H1 Antigen metabolism   MeSH
• Cell Line MeSH
• Immunotherapy MeSH
• Humans MeSH
• Ligands MeSH
• Histiocytoma, Malignant Fibrous * MeSH
• Mice, Nude MeSH
• Mice MeSH
• Sarcoma * pathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• B7-H1 Antigen MeSH
• Ligands MeSH

MicroRNAs belong to a group of short non-coding RNA molecules that are involved in the regulation of gene expression at multiple levels. Their function was described two decades ago, and, since then, microRNAs have become a rapidly developing field of research. Their participation in the regulation of cellular processes, such as proliferation, apoptosis, cell growth, and migration, made microRNAs attractive for cancer research. Moreover, as a single microRNA can simultaneously target multiple molecules, microRNAs offer a unique advantage in regulating multiple cellular processes in different cell types. Many of these cell types are tumor cells and the cells of the immune system. One of the most studied microRNAs in the context of cancer and the immune system is miR-155. MiR-155 plays a role in modulating innate and adaptive immune mechanisms in distinct immune cell types. As such, miR-155 can be part of the communication between the tumor and immune cells and thus impact the process of tumor immunoediting. Several studies have already revealed its effect on antitumor immune responses, and the targeting of this molecule is increasingly implemented in cancer immunotherapy. In this review, we discuss the current knowledge of miR-155 in the regulation of antitumor immunity and the shaping of the tumor microenvironment, and the plausible implementation of miR-155 targeting in cancer therapy.

• Keywords
• cancer, immunity, immunotherapy, miR-155, microRNA, tumors,
• Publication type
• Journal Article MeSH
• Review MeSH

Soft tissue sarcomas (STSs) are rare mesenchymal tumors. With more than 80 histological subtypes of STSs, data regarding novel biomarkers of strong prognostic and therapeutic value are very limited. To date, the most important prognostic factor is the tumor grade, and approximately 50% of patients that are diagnosed with high-grade STSs die of metastatic disease within five years. Systemic chemotherapy represents the mainstay of metastatic STSs treatment for decades but induces response in only 15-35% of the patients, irrespective of the histological subtype. In the era of immunotherapy, deciphering the immune cell signatures within the STSs tumors may discriminate immunotherapy responders from non-responders and different immunotherapeutic approaches could be combined based on the predominant cell subpopulations infiltrating the STS tumors. Furthermore, understanding the immune diversity of the STS tumor microenvironment (TME) in different histological subtypes may provide a rationale for stratifying patients according to the TME immune parameters. In this review, we introduce the most important immune cell types infiltrating the STSs tumors and discuss different immunotherapies, as well as promising clinical trials, that would target these immune cells to enhance the antitumor immune responses and improve the prognosis of metastatic STSs patients.

• Keywords
• IL-15, TILs, adoptive transfer, checkpoint inhibitors, immune cells, immunotherapy, sarcoma, trabectedin, tumor microenvironment,
• Publication type
• Journal Article MeSH
• Review MeSH