Objective To observe the expression of molecules on surface of dendritic cells (DC) in retinoblastoma (RB) patients, and investigate its relationship with immune function. Methods The peripheral blood of 50 normal subjects (control group) and 18 RB patients (RB group) were collected to proliferate the DC.The mixed lymphocyte reaction was performed on DC of the control and RB group to detect the antigen-presenting ability. The DC of control group was cultured in the supernate of SO-RB50 with the different concentration of 25% (group A), 50% (group B) and 75% (group C). Then the expression of HLA-DR, CD54 and CD80 on surface of DC were detected by flow cytometry (FCM). Results The Results of MLR showed that DC antigen-presenting ability was gradually enhanced with the increase of stimulation of the cell. And the DC antigen-presenting ability of the control group was superior to that of the RB group (P＜0.05). The expression of HLA-DR, CD54 and CD80 on surface of DC in the control group (12.14plusmn;2.52, 34.89plusmn;5.12, 10.93plusmn;3.1) were significantly higher than that in the RB group (7.33plusmn;2.20, 25.28plusmn;4.54, 7.89plusmn;3.75) (t=4.07, 3.96, 2.59; P＜0.05). The expression of HLA-DR, CD54 and CD80 on surface of DC in the group A, B and C (HLA-DR: 9.95plusmn;2.55, 6.48plusmn;1.82, 3.11plusmn;1.47; CD54: 34.75plusmn;4.92, 21.25plusmn;3.44,15.41plusmn;3.52; CD80: 9.15plusmn;2.18,5.05plusmn;2.01,2.90plusmn;1.10) were reduced in varying degrees compared with the control group; and with the increase of the concentration of supernate SO-RB50, the reduction was more evident (F=8.96,13.62, 20.72; P＜0.05). Conclusions The expression of molecules on surface of DC in RB patients is lower than that in the normal subjects. It is closely related to the functional deficiency of DC.
ObjectivesTo systematically review the clinical response rate of CD19 chimeric antigen receptor modified-T cells (CD19CART) in the treatment of B cell hematological malignancies.MethodsPubMed, EMbase, CNKI, WanFang Data and VIP databases were searched to collect cohort studies about CD19CART in the treatment of B cell hematological malignancies from 2000 to 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, a single rate meta-analysis was performed by R software and SPSS 16.0 software.ResultsA total of 13 prospective cohort studies were included. The results of single group rate meta-analysis showed that the overall pooled response rate of CD19 CART was 68% (95%CI 0.51 to 0.82). The 6 months and 1-year PFS after CD19 CART infused by Kaplan-Meier were 46% (95%CI 0.35 to 0.56) and 24% (95%CI 0.16 to 0.34), respectively. The median duration was 180 days (95%CI 138 to 222). The COX regression model showed lymphodepletion to be the only influence factor of PFS.ConclusionsCD19 CART has a good clinical response rate in the treatment of B cell hematological malignancies. Lymphodepletion is the only important impact on the response rate and PFS. Due to limited quality and quantity of included studies, more high quality studies are required to verify the above conclusions.
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.
It is very limited that the benefit of perioperative chemotherapy in early non-small cell lung cancer (NSCLC), and the 5-year survival rate is only 5% higher than surgery. Antibodies that block programmed cell death protein 1/programmed death receptor-ligand 1 significantly improve the survival of advanced NSCLC. The value of immunotherapy in early NSCLC is also being explored. This paper firstly summarized and analyzed the progress of immunotherapy in the perioperative period of NSCLC. Secondly, the safety and feasibility of surgical resection after neoadjuvant immunotherapy were discussed. Finally, the clinical value of different therapeutic efficacy prediction indicators was summarized, in order to clarify the current status of immunotherapy in the perioperative period, so as to improve the clinical benefits of early NSCLC patients.
Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.
Objectives To evaluate the effect and safety of mycobacterium vaccae in the treatment of recurrent treated pulmonary tuberculosis. Methods We searched PubMed (1997 to 2006), VIP (1997 to 2006), Wanfang database (1997 to 2006), The Cochrane Central Register of Controlled Trials (Issue 4, 2006) and the National Research Register (1996 to 2006). Randomized controlled trials comparing the mycobacterium vaccae immunotherapy group and the control group were included. Two reviewers independently performed data extraction and quality assessment. Data were analyzed using RevMan 4.2.2 software by The Cochrane Collaboration. Results Eleven high quality trials were included. Meta-analyses showed that mycobacterium vaccae immunotherapy plus chemotherapy resulted in higher sputum negative conversion rate (RR=1.36, 95%CI 1.21 to 1.54), higher lesion absorption rate (RR=1.39, 95%CI 1.13 to 1.72), and lower lesion non-absorption rate (RR=0.46, 95%CI 0.36 to 0.60), compared with the control group. These differences were all statistically significant. No serious adverse events were reported. Conclusion As an adjunct to chemotherapy, mycobacterium vaccae is helpful for patients with recurrent treated pulmonary tuberculosis in terms of improving cell-medicated immunity, sputum negative conversion and X-ray manifestation. More high quality studies are needed for further analysis.
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.
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.
Cancer immunotherapy refers to the therapeutic effect of controlling or eliminating tumor cells by interfering with the immune system to restore the anti-tumor immune response. Immune checkpoint inhibitor therapy that blocks programmed death -1/programmed cell death ligand-1/cytotoxic T lymphocyte-associated antigen 4 is one of the most commonly used tumor immunotherapies, with good efficacy and wide application. These drugs cause immune-related ocular complications such as uveitis, autoimmune retinopathy, and scleritis, which represent a new etiology of ocular inflammation. The ophthalmologist's grasp of the clinical characteristics of these diseases is helpful for timely diagnosis. At the same time, the ophthalmologist will work closely with the oncologist to make a comprehensive judgment based on the patient's primary tumor, survival prognosis, severity of adverse reactions related to ocular immunotherapy, and visual prognosis, and develop suitable therapeutic strategie, thereby saving the patients' vision and improving the quality of life.
ObjectiveTo systematically review the incidence of adverse skin reactions in lung cancer patients treated by immunotherapy. MethodsPubMed, Web of Science, The Cochrane Library, CNKI, WanFang Data and VIP databases were electronically searched to collect the studies on the incidence of skin adverse reactions in lung cancer patients treated with immunotherapy from June 2011 to June 2021. Two reviewers independently screened literature, extracted data and assessed the risk bias of the included studies. Meta-analysis was then performed by using Stata 15.0 software. ResultsA total of 63 studies were included, with a total sample size of 13 386 cases. The results of meta-analysis showed that the overall incidence of adverse skin reactions in lung cancer patients was 14.0% (95%CI 11.6% to 16.5%). ConclusionCurrent evidence shows that the incidence of adverse skin reactions in lung cancer patients with immunotherapy is high. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.