Résumé
Programmed death-1/programmed death-1 ligand (PD-1/PD-L) signal pathway plays an important role in tumor immune evasion.PD-1/PD-L blockade represented one of the most promising strategies of some tumor immunotherapy.Recently,more and more researches revealed the clinical significant of PD-1/PD-L signal pathway in esophageal cancer.This review briefly summarizes the research progress of PD-1/PD-L signal pathway in esophageal cancer,in order to provide some new methods in esophageal cancer immunotherapy.
Résumé
Immunotherapy targeted on programmed death 1 (PD-1) and programmed death 1 ligand (PD-L1) has been approved by US Food and Drug Administration (FDA) for the treatment of solid tumors such as melanoma, non-small cell lung cancer and renal cell carcinoma. Preliminary study on the gastrointestinal solid tumor has been carried out, which has shown favorable efficacies and promising application prospect. However, some disadvantages have appeared. This article reviews the progress of immunotherapy for gastric adenocarcinoma.
Résumé
Programmed death-1 (PD-1) occurs widely in a variety of human immune cells and tumor cells. When PD-1 is combined with programmed death-1 ligand (PD-L1), T-lymphocyte will be exhausted eventually resulting in tumor immune escape. Experiments in vitro and in vivo have demonstrated that inhibiting the binding of PD-1 with PD-L1, and blocking downstream signaling pathways can enhance endogenous anti-neoplastic immune effects. The expression of PD-1/PD-L1 is related to the clinical stage and prognosis of esophageal cancer patients, which may become the clinical biomarkers, serving as a new target for cancer immunotherapy.This paper reviews the relationship between PD-1/PD-L1 and esophageal cancer as well as the related treatment progress.
Résumé
Objective To explore the effect and mechanism of estrogen in mouse model with experimental autoimmune encephalomyelitis (EAE). Methods A mouse model with EAE was induced in female C57BL/6J mice by immunizing with MOG35-55 and CFA. The immunized mice were randomly divided into two groups. In treatment group, estrogen at 50 μmol/L was injected into mice by s.c. in a consecutive fashion from the day of myelin oligodendroglia glycoprotein (MOG) immunization until the day of experiment completion. Meanwhile, in control group, solvent was injected into mice by the same means. The disease score for EAE was recorded everyday. The secretion of TNF-α and IL-17A from cultured mouse splenic cell supernatant was tested by ELISA technique. The abundance of mRNA for TNF-α, IL-17A, PD-1 and PD-L1 in spinal cord was tested by real-time PCR method. The intracellular expression for TNF-α and IL-17A and the surface expression for CD4/PD-1, CD19/PD-L1, CD4/CD25/Foxp3, CD19/CD21/CD23 as well as CD19/ CD5/CD1dhigh of mouse splenocytes were tested by fluorescence activated cell sorting (FACS) method. Results The prophylactic treatment of estrogen could delay the progress in mouse EAE. Histopathological evaluation of mouse spinal cord specimen showed reduced demyelination and inflammatory cell invasion by estrogen treatment. Furthermore, both TNF-α and IL-17A production in estrogen treated mice was significantly downregulated compared to those in control group mice. However, the transcription and expression level for PD-1 in CD4+T cells and that for PD-L1 in CD19+B cells were observed to be upregulated in estrogen treated mice. Also, the percentages of CD19+CD21highCD23low and CD19+CD5+CD1dhigh Breg cells in splenocytes were augmented by estrogen treatment. In contrast, no changes were observed for the proportion of the splenic CD4+CD25+Foxp3+Tregs in mice composed to estrogen treatment with comparison to those in mice with vehicle treatment. Conclusion The prophylactic treatment of estrogen can delay the disease progress in EAE mice, likely through the upregulation of PD-1/PD-L1 pathway and Breg cells.
Résumé
Programmed death-1(PD-1)and its ligand(PD-L1)inhibitors are a novel kind of immune checkpoint blockers, which are the highlights of anti-tumor immune therapy. PD-1 inhibitors,such as nivolumab and pembrolizumab have been granted by the market authorization to treat melanoma and non-small cell lung cancer. Clinical trials of their efficacy and safety on renal cell carci?noma,bladder carcinoma and Hodgkin′s lymphoma are still in process. PD-L1 inhibitors atezolizumab,durvalumab and avelumab have been approved by FDA for treatment of urothelial carcinoma. Several other drugs are in phaseⅠclinical trials. This paper gives a brief summary of recent advances in the studies on PD-1/PD-L1 inhibitors.
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Immunosuppressive tumor microenvironment is a part of the tumor microenvironment that plays an immunosuppressive function.It consists of suppressor cells and inhibitory cytokines.In recent years,be-cause of its important role in tumor immunity,CAR-T and PD-1/PD-L1 signal pathway has become a hot top-ic of immunotherapy, which can suppress immune through different mechanisms to promote tumor progression. Therefore,taking more effective anti-tumor therapies against the above mechanisms is possible to rescue the pro-gress of tumor.In this article,the influence of immunosuppression microenvironment in CAR-T cell therapy and PD-1/PD-L1 signaling pathway in the anti-tumor process is reviewed.
Résumé
The inhibitors of programmed death 1 (PD-1)/PD-1 ligand (PD-L1) become a highlight in tumor immunotherapy and provide a new direction for immune-targeted therapy for cancer. More and more studies have confirmed that PD-1/PD-L1 inhibitors could improve effects and be well-tolerated. Early clinical trials of PD-1 inhibitors have shown significant clinical efficacy in various solid tumours. The unique role of the PD-1 pathway in lymphoma has been found gradually. This article summarized the advancement of PD-1 in B-cell lymphoma therapy.