Application of adoptive cell therapy in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) remains a global health challenge. Novel treatment modalities are urgently needed to extend the overall survival of patients. The liver plays an immunomodulatory function due to its unique physiological structural characteristics. Therefore, following surgical resection and radiotherapy, immunotherapy regimens have shown great potential in the treatment of hepatocellular carcinoma. Adoptive cell immunotherapy is rapidly developing in the treatment of hepatocellular carcinoma. In this review, we summarize the latest research on adoptive immunotherapy for hepatocellular carcinoma. The focus is on chimeric antigen receptor (CAR)-T cells and T cell receptor (TCR) engineered T cells. Then tumour-infiltrating lymphocytes (TILs), natural killer (NK) cells, cytokine-induced killer (CIK) cells, and macrophages are briefly discussed. The main overview of the application and challenges of adoptive immunotherapy in hepatocellular carcinoma. It aims to provide the reader with a comprehensive understanding of the current status of HCC adoptive immunotherapy and offers some strategies. We hope to provide new ideas for the clinical treatment of hepatocellular carcinoma.

miR-495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression.

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR-495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR-495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol-doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre-treatment with miR-495 before chemotherapy could improve the curative effect on MDR1-based MDR cancer.

Identification of signature genes and immune infiltration analysis in thyroid cancer based on PANoptosis related genes.

Background: Thyroid cancer is the most common malignancy of the endocrine system. PANoptosis is a specific form of inflammatory cell death. It mainly includes pyroptosis, apoptosis and necrotic apoptosis. There is increasing evidence that PANoptosis plays a crucial role in tumour development. However, no pathogenic mechanism associated with PANoptosis in thyroid cancer has been identified. Methods: Based on the currently identified PANoptosis genes, a dataset of thyroid cancer patients from the GEO database was analysed. To screen the common differentially expressed genes of thyroid cancer and PANoptosis. To analyse the functional characteristics of PANoptosis-related genes (PRGs) and screen key expression pathways. The prognostic model was established by LASSO regression and key genes were identified. The association between hub genes and immune cells was evaluated based on the CIBERSORT algorithm. Predictive models were validated by validation datasets, immunohistochemistry as well as drug-gene interactions were explored. Results: The results showed that eight key genes (NUAK2, TNFRSF10B, TNFRSF10C, TNFRSF12A, UNC5B, and PMAIP1) exhibited good diagnostic performance in differentiating between thyroid cancer patients and controls. These key genes were associated with macrophages, CD4+ T cells and neutrophils. In addition, PRGs were mainly enriched in the immunomodulatory pathway and TNF signalling pathway. The predictive performance of the model was confirmed in the validation dataset. The DGIdb database reveals 36 potential therapeutic target drugs for thyroid cancer. Conclusion: Our study suggests that PANoptosis may be involved in immune dysregulation in thyroid cancer by regulating macrophages, CD4+ T cells and activated T and B cells and TNF signalling pathways. This study suggests potential targets and mechanisms for thyroid cancer development.

Can pyroptosis be a new target in rheumatoid arthritis treatment?

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease of undefined etiology, with persistent synovial inflammation and destruction of articular cartilage and bone. Current clinical drugs for RA mainly include non-steroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, disease modifying anti-rheumatic drugs (DMARDs) and so on, which can relieve patients' joint symptoms. If we want to have a complete cure for RA, there are still some limitations of these drugs. Therefore, we need to explore new mechanisms of RA to prevent and treat RA radically. Pyroptosis is a newly discovered programmed cell death (PCD) in recent years, which is characterized by the appearance of holes in cell membranes, cell swelling and rupture, and the release of intracellular pro-inflammatory factors into the extracellular space, resulting in a strong inflammatory response. The nature of pyroptosis is pro-inflammatory, and whether it is participating in the development of RA has attracted a wide interest among scholars. This review describes the discovery and mechanism of pyroptosis, the main therapeutic strategies for RA, and the role of pyroptosis in the mechanism of RA development. From the perspective of pyroptosis, the study of new mechanisms of RA may provide a potential target for the treatment of RA and the development of new drugs in the clinics.

Sclerosing Epithelioid Fibrosarcoma of the Thoracic Vertebrae: An Fairly Unusual Case Report With a Short Review of Literature.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare subtype of soft tissue tumors, and SEF originating from the side of the spine is even rarer. We report that a 28-year-old young woman suffered from chest pain and back pain for 3 years, and thereafter she went to see a doctor because her condition deteriorated. Enhanced CT showed that the right posterior upper chest wall mass invaded the adjacent bone, and the boundary between the lesion and the surrounding tissues was relatively clear. She then underwent posterior tumor removal surgery. The pathological examination confirmed the diagnosis of SEF. In histomorphology, the tumor displayed a typical epithelioid clear cell morphology, accompanied by extensive vitrification and fibrosis, which better helped to differentiate the tumor from low grade fibromyxoid sarcoma, solitary fibrous tumor and other entities. The immunohistochemical analysis showed a diffuse positive reaction to MUC4, a highly specific marker of SEF, which was detected by Immunohistochemistry (IHC), and fluorescence in-situ hybridization (FISH) confirmed that the EWSR1 gene was rearranged, while the FUS gene was not rearranged. This is the first time that we have encountered such this rare case and thus report this case with updated literature related to this tumor.

Immunotherapeutic Potential of T Memory Stem Cells.

Memory T cells include T memory stem cells (TSCM) and central memory T cells (TCM). Compared with effector memory T cells (TEM) and effector T cells (TEFF), they have better durability and anti-tumor immunity. Recent studies have shown that although TSCM has excellent self-renewal ability and versatility, if it is often exposed to antigens and inflammatory signals, TSCM will behave as a variety of inhibitory receptors such as PD-1, TIM-3 and LAG-3 expression, and metabolic changes from oxidative phosphorylation to glycolysis. These changes can lead to the exhaustion of T cells. Cumulative evidence in animal experiments shows that it is the least differentiated cell in the memory T lymphocyte system and is a central participant in many physiological and pathological processes in humans. It has a good clinical application prospect, so it is more and more important to study the factors affecting the formation of TSCM. This article summarizes and prospects the phenotypic and functional characteristics of TSCM, the regulation mechanism of formation, and its application in treatment of clinical diseases.

Pyroptosis, a New Breakthrough in Cancer Treatment.

The way of cell death can be roughly divided into two categories: cell necrosis and PCD(programmed cell death). Pyroptosis is a kind of PCD, its occurrence depends on the gasdermin protein family and it will produce inflammatory response. With constant research in recent years, more and more evidences show that pyroptosis is closely related to the occurrence and development of tumors. The treatment of tumors is a big problem worldwide. We focus on whether we can discover new potential tumor markers and new therapeutic targets from the mechanism. If we can understand the mechanism of pyroptosis and clear the relationship between pyroptosis and the development of tumors, this may provide a new reference for clinical cancer treatment.