Introduction Inflammation is a defensive response of the organism to irritation which is manifested by redness, swelling, heat, pain and dysfunction. The inflammatory response underlies the role of various diseases. Ferroptosis, a unique modality of cell death, driven by iron-dependent lipid peroxidation, is regulated by multifarious cellular metabolic pathways, including redox homeostasis, iron processing and metabolism of lipids, as well as various signaling pathways associated with diseases. A growing body of evidence suggests that ferroptosis is involved in inflammatory response, and targeting ferroptosis has great prospects in preventing and treating inflammatory diseases. Materials and methods Relevant literatures on ferroptosis, inflammation, inflammatory factors and inflammatory diseases published from January 1, 2010 to now were searched in PubMed database. Conclusion In this review, we summarize the regulatory mechanisms associated with ferroptosis, discuss the interaction between ferroptosis and inflammation, the role of mitochondria in inflammatory ferroptosis, and the role of targeting ferroptosis in inflammatory diseases. As more and more studies have confirmed the relationship between ferroptosis and inflammation in a wide range of organ damage and degeneration, drug induction and inhibition of ferroptosis has great potential in the treatment of immune and inflammatory diseases.

The tumor microenvironment (TME) is a complex ecosystem, which includes many different types of cells, abnormal vascular systems, and immunosuppressive cytokines. TME serves an important function in tumor tolerance and escapes from immune surveillance leading to tumor progression. Indeed, there is increasing evidence that gut microbiome is associated with cancer in a variety of ways, as specific microbial signatures are known to promote cancer development and influence safety, tolerability, and efficacy of therapies. Studies over the past five years have shown that the composition of the intestinal microbiota has a significant impact on the efficacy of anticancer immunosurveillance, which contribute to the therapeutic activity of cancer immunotherapies based on targeting cytotoxic T lymphocyte protein 4 (CTLA-4) or programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) axis. In this review, we mainly discuss the impact of TME on cancer and immunotherapy through immune-related mechanisms. We subsequently discuss the influence of gut microbiota and its metabolites on the host immune system and the formation of TME. In addition, this review also summarizes the latest research on the role of gut microbiota in cancer immunotherapy.

Background: In the past decade, several antibodies directed against the PD-1/PD-L1 interaction have been approved. However, therapeutic antibodies also exhibit some shortcomings. Using small molecules to regulate the PD-1/PD-L1 pathway may be another way to mobilize the immune system to fight cancer. Method: 52,765 marine natural products were screened against PD-L1(PDBID: 6R3K). To identify natural compounds, a structure-based pharmacophore model was generated, following by virtual screening and molecular docking. Then, the absorption, distribution, metabolism, and excretion (ADME) test was carried out to select the most suitable compounds. Finally, molecular dynamics simulation was also performed to validate the binding property of the top compound. Results: Initially, 12 small marine molecules were screened based on the pharmacophore model. Then, two compounds were selected for further evaluation based on the molecular docking scores. After ADME and toxicity studies, molecule 51320 was selected for further verification. By molecular dynamics analysis, molecule 51320 maintains a stable conformation with the target protein, so it has the chance to become an inhibitor of PD-L1. Conclusions: Through structure-based pharmacophore modeling, virtual screening, molecular docking, ADMET approaches, and molecular dynamics (MD) simulation, the marine natural compound 51320 can be used as a small molecule inhibitor of PD-L1.