Chronic cerebral hypoperfusion (CCH) plays an important role in the occurrence and development of vascular dementia (VD). Recent studies have indicated that multiple stages of immune-inflammatory response are involved in the process of cerebral ischemia, drawing increasing attention to immune therapies for cerebral ischemia. This study aims to identify potential immune therapeutic targets for CCH using bioinformatics methods from an immunological perspective. We identified a total of 823 differentially expressed genes associated with CCH, and further screened for 9 core immune-related genes, namely RASGRP1, FGF12, SEMA7A, PAK6, EDN3, BPHL, FCGRT, HSPA1B and MLNR. Gene enrichment analysis showed that core genes were mainly involved in biological functions such as cell growth, neural projection extension, and mesenchymal stem cell migration. Biological signaling pathway analysis indicated that core genes were mainly involved in the regulation of T cell receptor, Ras and MAPK signaling pathways. Through LASSO regression, we identified RASGRP1 and BPHL as key immune-related core genes. Additionally, by integrating differential miRNAs and the miRwalk database, we identified miR-216b-5p as a key immune-related miRNA that regulates RASGRP1. In summary, the predicted miR-216b-5p/RASGRP1 signaling pathway plays a significant role in immune regulation during CCH, which may provide new targets for immune therapy in CCH.
The specific binding of T cell receptors (TCRs) to antigenic peptides plays a key role in the regulation and mediation of the immune process and provides an essential basis for the development of tumour vaccines. In recent years, studies have mainly focused on TCR prediction of major histocompatibility complex (MHC) class I antigens, but TCR prediction of MHC class II antigens has not been sufficiently investigated and there is still much room for improvement. In this study, the combination of MHC class II antigen peptide and TCR prediction was investigated using the ProtT5 grand model to explore its feature extraction capability. In addition, the model was fine-tuned to retain the underlying features of the model, and a feed-forward neural network structure was constructed for fusion to achieve the prediction model. The experimental results showed that the method proposed in this study performed better than the traditional methods, with a prediction accuracy of 0.96 and an AUC of 0.93, which verifies the effectiveness of the model proposed in this paper.
Brain metastases are the most common intracranial malignant tumors in adults. Radiotherapy isa common treatment for brain metastases. In particular, stereotactic radiosurgery can control tumors well, and can significantly reduce the impact on cognitive function compared with whole brain radiation therapy. Immune checkpoint inhibitors have less toxic side effects in the treatment of patients with advanced tumors, and show good survival advantages. This article introduces radiotherapy, immunotherapy, stereotactic radiosurgery combined with immune checkpoint inhibitors for brain metastases, discusses the mechanism of stereotactic radiosurgery combined with immune checkpoint inhibitors, and its therapeutic value and research progress in brain metastases, aiming to provide a theoretical basis for the better application of stereotactic radiosurgery combined with immune checkpoint inhibitors to brain metastases.
ObjectiveTo explore the antitumor effect of tumor vaccine fused from dendritic cells (DC) and Walker-256 cancer cells on implanted liver cancer in rats and the related mechanism of inhibition for tumor angiogenesis. MethodsWalker-256 cancer cells and mature DC were fused by 50% polyethylene glycol method for preparation of DC-Walker-256 fusion vaccines. Implanted liver cancer models were established through operations on healthy male SD rats at the age of 6－8 weeks. All the rats were divided into four groups, and rats in each group were injected subcutanely with fusion vaccine (group), mixed cultured cells (group), simple DC (group), and PBS (blank control group), respectively. On 28 d after making model, the rats were put to death, the tumor was observed and pathological essays were prepared. All rats’ spleens were collected and prepared into lymphocyte to detect antigenic specificity cytotoxic T lymphocyte (CTL) by enzymelinked immunosorbent spot (ELISPOT) method. The expressions of VEGF, ANG-1, ANG-2, and MVD were detected by immunohistochemistry. ResultsThe numbers of rats survived in the fusion vaccine group, mixed culture cells group, simple DC group, and blank control group was 8, 5, 6, and 3, respectively. The rats in the other three groups except for fusion vaccine group were manifested as inaction, anorexia, and gloomy fur in some degree as well as ascites. The tumorigenesis was found in all survival rats except for two in the fusion vaccine group. The weight of liver tumors of rats in the fusion vaccine group 〔(32.4±9.2) g〕 was significantly lighter than that in the mixed culture cells group 〔(67.3±5.1) g, P=0.031〕, simple DC group 〔(75.0±8.3) g, P=0.019〕, and blank control group 〔(86.6±10.5) g, P=0.008〕, respectively. The number of tumorspecific CTL of rats in the fusion vaccine group was also significantly higher than that in the other three groups (P=0.019, P=0.025, and P=0.001, respectively). The MVD of tumor tissue in the fusion vaccine group was (24.12±2.32) vessels/HP, which was significantly lower than that in the mixed culture cells group 〔(40.34±1.29) vessels/HP, P=0.025〕, simple DC group 〔(42.36±3.16) vessels/HP, P=0.035〕, and blank control group 〔(56.48±5.16) vessels/HP, P=0.006〕, respectively. The MVD of tumor tissue in the mixed cultured cells group and simple DC group was similar (P=0.165), however, which was significantly lower than that in the blank control group (P=0.040 and P=0.043). The positive rate of VEGFA protein expression was 23.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (42.5%, P=0.031), simple DC group (61.3%, P=0.019), and blank control group (89.6%, P=0.003), respectively. The positive rate of VEGF-A protein expression in the mixed cultured cells and simple DC groups was similar (P=0.089), however, which was significantly lower than that in the blank control group (P=0.027 and P=0.038). The positive rate of ANG-1 protein expression in the fusion vaccine group (43.2%) was not different from that in the mixed culture cells group (46.3%, P=0.292), simple DC group (51.3%, P=0.183), or blank control group (49.6%, P=0.179), respectively, and the difference of pairwise comparison in latter three groups was not significant (P=0.242, P=0.347, and P=0.182). The positive rate of ANG2 protein expression was 19.2% in the fusion vaccine group, which was significantly lower than that in the mixed culture cells group (62.3%, P=0.007), simple DC group (67.3%, P=0.005), and blank control group (71.6%, P=0.004), respectively, however, the difference of pairwise comparison in latter three groups was not significant (P=0.634, P=0.483, and P=0.379). ConclusionFused vaccine can induce CD8+ CTL aiming at tumor cells and establish the effective antitumor immunity in vivo and also downregulate the level of VEGF and ANG-2 to suppress tumor angiogenesis and thereby achieve the purpose of curing tumor.
Tumor immunotherapy includes immune checkpoint inhibitor (ICI), tumor vaccines, and adoptive cell therapy. Immunotherapy, as the main systemic treatment for advanced malignant tumors, kills tumor cells by activating the immune system and prolongs the survival of patients. However, excessive immune responses can cause immune-related adverse events (irAE), causing damage to systemic tissues. ICI are the main tumor immunotherapy drugs that cause optic nerve irAE. The most common optic nerve irAE are optic neuritis, only a few patients appeared arteritic anterior ischemic optic neuropathy. Sudden painless loss of bilateral vision is the most common clinical manifestation. In severe cases, the vision decrease to no light perception. Early diagnosis and early adequate glucocorticoid treatment can improve the symptoms. Therefore, neuro-ophthalmologists and oncologists should know the clinical characteristics of optic nerve irAE, in order to diagnose and treat early and improve the prognosis.
Metastatic renal cell carcinoma accounts for 20%-30% of newly diagnosed renal cell carcinoma and its prognosis is poor. It is not sensitive to radiotherapy or chemotherapy, and traditional cytokine therapy has limited efficacy in patient with metastatic renal cell carcinoma. In recent years, with the emergence of targeted drugs and immune checkpoint inhibitors, the survival of patients with metastatic renal cancer has been greatly improved. This article reviews treatment and research progress of metastatic renal cell carcinoma. It mainly introduces the medical treatment, including cytokine therapy, targeted therapy and emerging immunotherapy, and further analyzes the value of cytoreductive nephrectomy in the context of targeted therapy. The purpose of this article is to provide evidence for reasonable choices of treatment regimens in order to better guide clinical treatment.
Immunotherapy is an important treatment method in tumor therapy. Among them, programmed death-1/programmed death ligand-1 inhibitors are the immune preparations with mature application and great survival benefit at present. Programmed death-1/programmed death ligand-1 inhibitors brought better clinical benefits to patients with esophageal cancer and provided more favorable choice for the treatment of esophageal cancer. This article introduces the mechanism of action, application in esophageal cancer, and efficacy predictors of programmed death protein-1/programmed death protein ligand-1 inhibitors, aiming to provide a theoretical basis for the more rational use of programmed death protein-1/programmed death protein ligand-1 inhibitors in patients with esophageal cancer.
Lung microbiome is defined as the specific microbiota of lung. Lung microbiome can make the lung in a state of chronic inflammation through direct destruction, activation of inflammatory cells and release of inflammatory factors, and then progress to lung cancer. There are significant differences in lung microbiome between lung cancer patients and healthy people. Some specific microbial flora can be used as a diagnostic marker of lung cancer. Specific microbial communities are related to the efficacy of immunotherapy, and microbial composition may be used as a marker of immune-related adverse events. There are both challenges and opportunities for research on the relationship between lung microbiome and lung cancer. This review will focus on the significance and value of lung microbiome in the occurrence, diagnosis and immunotherapy of lung cancer, in order to provide a reference for basic and clinical researchers in related fields.
Neuromyelitis optica spectrum disorders (NMOSD) are a group of inflammatory disorders of the central nervous system characterized by episodes of immune-mediated demyelination and axonal damage mainly involving optic nerves and spinal cord. Neuromyelitis optica related optic neuritis (NMO-ON) is a common neuro-ophthalmic disease which often results in permanent blindness. The discovery of aquaporin 4 antibodies confirms that neuromyelitis optica is a distinct disease entity different from multiple sclerosis. In patients with NMO-ON, the correct therapeutic approach has to recognize two distinct clinical situations: treatment of the acute attacks and prevention of the relapses. With the in-depth study of the pathogenesis of NMOSD, new treatments are emerging in different targets of the disease. This review gives an update of latest treatment of NMO-ON, emphasizing both current situation and future immunotherapy strategies.
【Abstract】Objective To explore the effect against gastric cancer induced by Newcastle disease virus modified autologous tumor vaccine （NDV-ATV）pulsed dendritic cells(DCs). Methods The Newcastle disease virus infected the gastric cancer lines (MNK45) and was lost its activity. Peripheral blood mononuclear cell (PBMC) were cultured under condition of recombinant human granulocyte macrophage-colony stimulating factor (1 000 u/ml)+IL-4(1 000 u/ml) + TNF-α(100 ng/ml). The tumor antigen specific cytotoxic T lymphocytes (CTL) was generated from activated autologous T cell by the Newcastle disease virus infected the MNK45 pulsed DC. And Cyto Tox 96TM in vitro assayed the cytotoxicity of CTL to MNK45. Thawed gastric cancer cell antigen were used as control in these experiments. Results The killing rate of MNK45 by antigen specific CTL reached (90.15±9.82)%, which was nearly twice as high as that of control(60.57±5.74)%. The CTL had much higher cytotoxicity to different differentiated type of gastric cancer cells such as MGC803〔(52.23±6.45)% 〕 and SGC7901〔 (61.75±8.84)%〕, as compared with LOVO〔(9.11±3.42)%〕 and HepG2 〔 (8.30±3.12)%〕tumor cells(P＜0.05). Conclusion Efficient and specific of against gastric cancer immunoreaction can be induced in virtue of NDV-ATV pulsed DCs, NDV-ATV loaded DCs might provide a new kind of theraputic means for gastric cancer.