ObjectiveTo summarize the biomarkers related to the efficacy of immune checkpoint inhibitors for hepatocellular carcinoma (HCC).MethodReviewed and summarized the literatures on the basic and clinical application of biomarkers related to programmed cell death protein 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and their combination with targeted therapy.ResultsThe combination of immunotherapy and targeted therapy had brought great hope for the treatment of patients with advanced HCC, but there were still some patients who could not benefit from it. Recent studies had shown that expression of PD-L1 in tumor tissue, tumor mutational burden, tumor-infiltrating lymphocytes, peripheral immune cells, circulating tumor DNA, gut microbiome, and so on, could predict the efficacy of immunotherapy or targeted therapy combined with immunotherapy for HCC.ConclusionsThere is no specific biomarker to predict the efficacy of immunotherapy and its combination regimen for HCC. More prospective studies are needed to confirm the predictive value of these biomarkers and to establish a multi-factor predictive model or immune score to screen patients who may benefit, which is of great significance for precise immunotherapy of HCC.
ObjectiveTo summarize the research progress on the role of exosomes derived from different sources in hepatic stellate cells.MethodThe experimental studies and clinical applications of exosomes from different cell sources effected on hepatic stellate cells were reviewed.ResultsIn the occurrence and development of liver fibrosis pathological physiological process, the activation, proliferation, migration, apoptosis of hepatic stellate cells played the important roles on the development of liver fibrosis. In recent years, the study found that the exosomes derived from different sources contained active protein, mRNA, microRNA, long noncoding RNA, and lipid components involved in the biological function of hepatic stellate cells, realized the communication between cells, which played the important regulatory role in the formation of liver fibrosis.ConclusionsExosomes derived from different sources and their contents play an important regulatory role in occurrence and development of liver fibrosis. In the future, exosomes might become a new non-invasive diagnostic method for liver fibrosis to help its early diagnosis, and might also be used as a biological active carrier to achieve its targeted therapy for targeted tissues and cells.
Objective To summarize the important role of tumor associated neutrophils (TANs) in the occurrence, development and prognosis of hepatocellular carcinoma (HCC). Methods The basic and clinical application research literatures on the correlation between TANs and the occurrence, development and prognosis of HCC were reviewed. Results As the most abundant inflammatory cells in human body, neutrophils were also an important part of the immunosuppressive microenvironment of HCC, which was closely related to the occurrence and development, immune escape and drug sensitivity of HCC. In the tumor microenvironment, the interaction between TANs, HCC cells and other components such as neutrophil extracellular traps was regulated by a variety of signal pathways. Some parameters related to neutrophils, such as neutrophils to lymphocytes ratio, had been used as effective biomarkers for predicting the clinical prognosis of HCC patients. Conclusions The exact role of neutrophils in HCC remains to be further studied. With the continuous accumulation of research results on the function of tumor associated immunosuppressive neutrophils and new therapies targeting neutrophils, more patients with HCC will benefit from immunotherapy and personalized targeted therapy.