Research progress regarding programmed cell death 1/programmed cell death ligand 1 inhibitors combined with targeted therapy for treating hepatocellular carcinoma

In recent years,a number of targeted therapeutic agents have achieved success in phase III trials in patients with advanced hepatocellular carcinoma(HCC),including sorafenib,lenvatinib,and regorafenib.Immunotherapy is considered to be an effective treatment for advanced HCC.Immune checkpoint inhibitors targeting programmed cell death 1(PD-1)/programmed cell death ligand 1(PDL1)are important antitumor immunotherapy agents that represent breakthroughs in the treatment of advanced HCC.However,treating advanced HCC is still a great challenge,and the need for new treatments remains urgent.This review briefly summarizes the research progress in the use of PD-1/PD-L1 inhibitors combined with targeted therapy for treating HCC.

Research progression of PD-1/PD-L1 in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Despite great progress in the development of target agents, most people who do not harbor a mutation do not benefit from these agents. Immunotherapy, which stimulates the body's immune system to improve the anti-tumor immunity effect, is a new therapeutic method for non-small cell lung cancer(NSCLC). Programmed cell death 1(PD-1) and its ligand(PD-L1) belong to the CD28/B7 immunoglobulin super-family and are co-stimulatory molecules that show negative regulation effects. Combined with its ligand, PD-1 can modulate the tumor microenvironment, enabling tumor cells to escape host immune surveillance and elimination and play a key role in the clinical significance of NSCLC. An increasing number of clinical trials have suggested that immune checkpoint inhibitors, including anti-PD-1 and anti-PD-L1 monoclonal antibodies, are beneficial and safe for NSCLC. Here, we review the brief history of PD-L1 as a biomarker, mechanism of action, and critical role of PD-1/PD-L1 in the treatment of NSCLC as well as the current research status and future directions.

Faecal microbiota transplantation enhances efficacy of immune checkpoint inhibitors therapy against cancer

Even though immune checkpoint inhibitors(ICIs)are effective on multiple cancer types,there are still many non-responding patients.A possible factor put forward that may influence the efficacy of ICIs is the gut microbiota.Additionally,faecal microbiota transplantation may enhance efficacy of ICIs.Nevertheless,the data available in this field are insufficient,and relevant scientific work has just commenced.As a result,the current work reviewed the latest research on the association of gut microbiota with ICI treatments based on anti-programmed cell death protein 1 antibody and anti-cytotoxic T-lymphocyte-associated protein 4 antibody and explored the therapeutic potential of faecal microbiota transplantation in combination with ICI therapy in the future.

Necrostatin-1 protection of dopaminergic neurons

Necroptosis is characterized by programmed necrotic cell death and autophagic activation and might be involved in the death process of dopaminergic neurons in Parkinson＇s disease. We hypothesized that necrostatin-1 could block necroptosis and give protection to dopaminergic neurons. There is likely to be crosstalk between necroptosis and other cell death pathways, such as apoptosis and autophagy. PC12 cells were pretreated with necroststin-1 1 hour before exposure to 6-hydroxydopamine. We examined cell viability, mitochondrial membrane potential and expression patterns of apoptotic and necroptotic death signaling proteins. The results showed that the autophagy/lysosomal pathway is involved in the 6-hydroxydopamine-induced death process of PC12 cells. Mitochondrial disability induced overactive autophagy, increased cathepsin B expression, and diminished Bcl-2 expression. Necrostatin-1 within a certain concentration range（5–30 μM） elevated the viability of PC12 cells, stabilized mitochondrial membrane potential, inhibited excessive autophagy, reduced the expression of LC3-II and cathepsin B, and increased Bcl-2 expression. These findings suggest that necrostatin-1 exerted a protective effect against injury on dopaminergic neurons. Necrostatin-1 interacts with the apoptosis signaling pathway during this process. This pathway could be a new neuroprotective and therapeutic target in Parkinson＇s disease.