ABSTRACT
The POFUT1 gene, known to be up-regulated in various tumor tissues and associated with tumor biology, has yet to be explored for its potential role in immune response regulation and tumor immune microenvironment. The normalized pan-cancer dataset (TCGA Pan-Cancer) was downloaded from the UCSC database, followed by analysis of POFUT1 expression in various tumors and functional enrichment analysis. The correlation between POFUT1 expression levels and patient prognosis was assessed. GSEA of POFUT1 based on low-grade glioma (LGG) samples and immune infiltration analyses of LGG and glioblastoma (GBM) were conducted. The correlation between POFUT1 expression levels and infiltration levels of 22 immune cells in LGG and GBM was examined, as well as the correlation between immune cell infiltration levels and LGG patient prognosis. Additionally, the relationship between POFUT1 expression levels and characteristic gene expression of identified immune cells was evaluated. Lastly, external dataset validation was performed using the integrated CGGA dataset. Significant differences were observed in POFUT1 expression levels across 20 tumor types. High POFUT1 expression correlated with poor prognosis in GBMLGG, and LGG patients. Enrichment analysis and GSEA of POFUT1 in LGG demonstrated involvement in tumor-related and immune-related pathways. A positive correlation was identified between POFUT1 expression levels and infiltration levels of resting memory CD4+ T cells, as well as M2 macrophages or M2-like TAMs in the LGG immune microenvironment, potentially contributing to poor prognosis. External dataset validation revealed a positive correlation between M2 macrophages or M2-like TAMs and POFUT1 expression levels in LGG, and a negative correlation with LGG patient prognosis. POFUT1's negative impact on LGG prognosis may result from its influence on M2 macrophage and M2-like TAM infiltration levels within the immune microenvironment. This suggests its potential as a prognostic predictor and therapeutic target for LGG.
ABSTRACT
PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.
Subject(s)
Immune Checkpoint Inhibitors , Psoriasis , Humans , Psoriasis/drug therapy , Psoriasis/chemically induced , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Immunotherapy/adverse effects , Disease ProgressionABSTRACT
Abstract PD-1 (programmed Death-1) immune checkpoint inhibitors have provided significant benefits to tumor patients. However, a considerable proportion of the patients develop immune-related adverse events (irAEs), of which cutaneous irAEs (cirAEs, e.g., psoriasis) occur relatively early. This review provides an overview of the current progress in psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. It not only describes the relevant influencing factors but also theoretically analyzes the immunological mechanisms that lead to the onset or exacerbation of psoriasis. Finally, the authors present guidelines for the treatment of psoriasis de novo or exacerbation by PD-1 checkpoint inhibitors. The review is intended to assist dermatologists in the early recognition and effective individualized management of such cirAE, which is helpful to continue or adjust the tumor-targeted immunotherapy on the basis of ensuring the quality of life of tumor patients.