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Objective:To investigate the expression of long non-coding RNA(lncRNA) ZFP36-AS1 in bladder cancer and the effect of ZFP36-AS1/miR-221 axis on the proliferation and immune escape of bladder cancer cells.Methods:The expression difference of ZFP36-AS1 in bladder cancer tissues was analyzed by cBioPortal database. Real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) was used to analyze the expression difference of ZFP36-AS1 in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637). MGH-U3 cells were randomly divided into negative control (NC) group and ZFP36-AS1 group, which were transfected with pcDNA3.1-NC plasmid and pcDNA3.1-ZFP36-AS1 plasmid, respectively. Colony formation assay and flow cytometry were used to analyze the proliferation activity and cell cycle of MGH-U3 cells, respectively. T lymphocytes were co-cultured with MGH-U3 cells in each group, and the levels of interleukin-10 (IL-10), γ-interferon (IFN-γ), and interleukin-4 (IL-4) in the supernatants of each group were detected by enzyme-linked immunosorbent assay (ELISA). The dual-luciferase reporter gene assay verified the targeting relationship between ZFP36-AS1 and miR-221. The effect of ZFP36-AS1 on the expression of miR-221 in MGH-U3 cells was detected by RT-qPCR. Western blotting was used to detect the effect of ZFP36-AS1/miR-221 axis on the protein expression of CDK3, Cyclin C, CDK5, Cyclin D1 and Cyclin D3 in MGH-U3 cells.Results:Compared with normal bladder tissue, ZFP36-AS1 was abnormally low-expressed in bladder cancer tissue ( P<0.01). Compared with SV-HUC-1 cells, ZFP36-AS1 was abnormally low-expressed in bladder cancer cell lines (J82, RT-4, MGH-U3, 5637) ( P<0.01), and the expression was lowest in MGH-U3 cells ( P<0.01). The number of MGH-U3 cell colonies formed in the NC group and the ZFP36-AS1 group were (220.80±34.65) and (77.84±19.11), respectively, and the number of MGH-U3 cell colonies formed in the ZFP36-AS1 group was significantly down-regulated, the difference was statistically significant ( P<0.01). The proportions of G 0/G 1 phase cells in NC group and ZFP36-AS1 group were (48.04±2.89)% and (72.89±3.46)%, respectively, and the proportion of S phase cells were (35.38±2.98)% and (20.62±2.56)%, respectively. The proportion of G 2/M stage cells was (16.59±1.46)% and (6.48±1.50)%, respectively. The proportion of cells in G 0/G 1 phase were up-regulated in ZFP36-AS1 group ( P<0.01), and the proportion of cells in S phase and G 2/M phase were both down-regulated ( P<0.01). Compared with the NC group, the levels of IL-4 and IFN-γ in the ZFP36-AS1 group were significantly up-regulated ( P<0.01), and the level of IL-10 was significantly down-regulated ( P<0.01). ZFP36-AS1 can target miR-221 ( P<0.01). The relative expression of miR-221 in the NC group and the ZFP36-AS1 group was 6.84±1.35 and 1.00±0.21, respectively. Compared with the NC group, overexpression of ZFP36-AS1 could significantly inhibit the expression of miR-221 ( P<0.01). Compared with the NC group, the expressions of CDK3, Cyclin C, CDK5, Cyclin D1, and Cyclin D3 in the ZFP36-AS1 group were significantly decreased. Conclusion:ZFP36-AS1 is abnormally low-expressed in bladder cancer, and it reduces the proliferation activity of bladder cancer cells and inhibits their immune escape by inhibiting the expression of miR-221.
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Objective To investigate the influences of circular RNA(circRNA)DCUN1D4 on the proliferation,apoptosis and immune escape of lung cancer cells by regulating the microRNA(miR)-18a-5p/fructose-1,6-bisphosphatase 1(FBP1)axis.Methods The human lung cancer cell lines H1975,H1650,A549 and SPCA-1 and human normal lung epidermal cells HPL-1 were selected,qRT-PCR was used to detect the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA in various cells.A549 cells in logarithmic growth phase were selected and divided into the blank group,circDCUN1D4 overexpression plasmid(circDCUN1D4)group,overexpression plasmid negative control(NC)group,circDCUN1D4+miR-18a-5p mimics negative control(circDCUN1D4+mimics NC)group,and circDCUN1D4+miR-18a-5p mimics group.The cell viability of each group was detected by CCK-8 method,the cell apoptosis was detected by flow cytometry,the expression levels of circDCUN1D4,miR-18a-5p and FBP1 mRNA of cells in each group were detected by qRT-PCR,the expression levels of FBP1,caspase-3,Ki67,proliferating cell nuclear antigen(PCNA)and programmed death ligand-1(PD-L1)were detected by Western blot,the targeting relationships of miR-18a-5p with circDCUN1D4 and FBP1 were verified by dual luciferase assay.Results Compared with HPL-1 cells,the mRNA expressions of circDCUN1D4 and FBP1 were significantly decreased(P<0.05),and the expression of miR-18a-5p was significantly increased(P<0.05).miR-18a-5p had targeting relationships with circDCUN1D4 and FBP1,respectively.Compared with the blank group and NC group,the OD values at 24 hours and 48 hours,and the expressions of Ki67,PCNA,miR-18a-5p and PD-L1 of cells in the circDCUN1D4 group were significantly decreased(P<0.05),and the apoptosis rate,and the expressions of circDCUN1D4,FBP1 and caspase-3 were significantly increased(P<0.05).Overexpression of miR-18a-5p reversed the inhibitory effect of circDCUN1D4 on the malignant behavior of lung cancer cells(P<0.05).Conclusion Overexpression of circDCUN1D4 can promote lung cancer cell apoptosis,inhibit lung cancer cell proliferation and immune escape,and its mechanism may be related to the regulation of miR-18a-5p/FBP1 axis.
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Objective:To study the influences of circular RNA ras homolog family member T1(CircRHOT1)on the prolifera-tion,apoptosis and immune escape of breast cancer cells by regulating the miR-187-3p/sex-determining region Y-box protein 4(SOX4)axis.Methods:Real-time quantitative PCR and Western blot were used to detect the expressions of CircRHOT1,miR-187-3p and SOX4 in human normal breast epithelial cells MCF-10A and breast cancer cells MCF-7,Hs-578T and MDA-MB-231 in vitro;MCF-7 cells cultured in vitro were randomly separated into control group,CircRHOT1 knockdown(transfected with CircRHOT1 siRNA plasmid)group,miR-187-3p mimics(transfected with miR-187-3p mimics)group,co-transfection negative control(transfected with empty plasmid and miR-187-3p inhibitor negative control)group,and CircRHOT1 knockdown+miR-187-3p inhibitor(transfected with CircRHOT1 siRNA plasmid and miR-187-3p inhibitor)group.After grouping and transfection,real-time quantitative PCR and Western blot were used to detect the expressions of CircRHOT1,miR-187-3p and SOX4 in each group;cell proliferation in each group was detected by EdU staining and plate colony formation assay;cell apoptosis in each group was detected by flow cytometry;im-munofluorescence staining was used to detect the ratio of apoptosis-related proteins Bax and Bcl-2(Bax/Bcl-2)expressions in each group.The cells of each group were co-cultured with human peripheral blood lymphocytes and transfected into groups,flow cytometry was used to detect the proportion of activated CD8+T cells in human peripheral blood lymphocytes in each group;the killing rate of human peripheral blood lymphocytes to MCF-7 cells in each group was detected by MTT assay.Dual-luciferase reporter assay was used to detect the targeted regulation of miR-187-3p and miR-187-3p on SOX4 by CircRHOT1 in MCF-7 cells.Results:Compared with human normal breast epithelial cells MCF-10A,human breast cancer MCF-7,Hs-578T and MDA-MB-231 cells had obviously higher protein and mRNA expression of CircRHOT1 and SOX4(P<0.05),and obviously lower expression of miR-187-3p(P<0.05).Com-pared with control group,the protein and mRNA expression of SOX4,EdU positive rate and colony formation rate of cells in Circ-RHOT1 knockdown group and miR-187-3p mimics group decreased(P<0.05),the expression of miR-187-3p,apoptosis rate,Bax/Bcl-2,the proportion of activated CD8+T cells in human peripheral blood lymphocytes and the killing rate on MCF-7 cells increased(P<0.05).Compared with CircRHOT1 knockdown group,there was no obvious difference in the expression of CircRHOT1 in the CircRHOT1 knockdown+miR-187-3p inhibitor group(P>0.05),the protein and mRNA expression of SOX4,EdU positive rate and colony formation rate of cells increased(P<0.05),the expression of miR-187-3p,apoptosis rate,Bax/Bcl-2,the proportion of activated CD8+T cells in human peripheral blood lymphocytes and the killing rate on MCF-7 cells decreased(P<0.05);there was no obvious difference in the indexes of cells in co-transfection negative control group(P>0.05).Conclusion:Knockdown of CircRHOT1 can reduce the expression of SOX4 by up-regulating miR-187-3p,thereby attenuating the proliferative activity of breast cancer cells and promoting their apoptosis.It can also inhibit the activation of CD8+T cells and enhance their cancer cell cytotoxicity,thereby weakening immune evasion of breast cancer cells.
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Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.
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【Objective】 To investigate asymptomatic infection of hepatitis B virus(HBV) among hepatitis B vaccinated donors in Shenzhen, and analyze its serological and molecular characteristics. 【Methods】 The HBsAg ELISA positive blood samples of blood donors born after 1992 were collected. HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc were further detected by Roche electrochemiluminescence immunoassay (ECL). BCP/PC and S regions were amplified by Nested-PCRs, HBV DNA quantification were adopted by qPCR simultaneously, and the sequences were also analyzed. 【Results】 A total of 46 632 blood samples of donors(31 612 males and 15 020 females) from December 2020 to January 2022 collected, and 99 samples with HBsAg ELISA positive were screened out. After tested by ECL, Nested-PCRs, and real-time fluorescence PCR, 61 were confirmed HBsAg positive, with the positive rate at 0.13% (61/46 632), including 49 males (0.16%, 49/31 612) and 12 females (0.08%, 12/15 020). The HBsAg positive rate of males was higher than that of females (P<0.05). 50 out of 61 sequences for S region were obtained. By phylogenetic analysis, there were 46 cases of type B (92%, 46/50, 38 males and 8 females), 4 cases of type C (8%, 4/50, 3 males and 1 female). The high frequency mutations observed in S region were N40S (8/46,17.39%), G44E (7/46,15.22%), Q129H/R(6/46,13.04%), Y161F/S(7/46, 15.22%), V179A(4/46,8.70%), S53L(2/4,50%), C69T(2/4,50%) and I126S/T(2/4,50%), including the immune escape mutations Q129R and T/I126A/N/S/T. 【Conclusion】 Hepatitis B vaccination can significantly reduce the positive rate of HBsAg and increase the safety of blood transfusion. The high frequency immune escape mutations have become a potential risk of blood safety, and need to be further explored.
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Leukemia is a critical disease with a high incidence and extremely high fatality rate.Immune escape by leukemia stem cells(LSC)is the main factor for recurrence and progression after remission.Clinical diagnosis and treatment by Traditional Chinese Medicine(TCM)have distinct advantages of syndrome differentiation and treatment.Based on the purpose of diagnosis and treatment,leukemia treatment by TCM emphasizes the harmony of yin and yang to restore human functions,which is conducive to improve autoimmunity and conforms to the mechanism of intervention for tumor cell immune escape.This article discusses the mechanism and research progress of TCM interventions in LSC immune escape based on literature and TCM theory.
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Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.
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ObjectiveTo study the effect and mechanism of Xiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine on immune escape in Lewis lung cancer mice. MethodA total of 60 specific-pathogen-free （SPF）-grade C57BL/6J male mice were injected subcutaneously with 0.2 mL of Lewis cell suspension （containing 2×106 cells·mL-1） in the right mid-axillary line. After 7 days， the mice that had been successfully modeled were randomly divided into six groups： the model group， the cisplatin group， the Xiangsha Liu Junzitang low-， medium-， and high-dose groups， and the combined group， with 10 mice in each group. The Xiangsha Liu Junzitang low-， medium- and high-dose groups were gavaged with 17.88， 35.75， 71.50 g·kg-1 Xiangsha Liu Junzitang solution once a day， respectively， and the dosage of cisplatin intraperitoneally injected into the mice was converted to 5 mg·kg-1 twice a week， and the tumour volumes of each group were measured every two days. The intervention lasted for 14 consecutive days. At the end of treatment， the tumour mass of mice in each group was weighed and the tumour inhibition rate was calculated. The morphological characteristics of tumours in each group were observed by hematoxylin-eosin （HE） staining. Fluorescent quantitative real-time polymerase chain reaction （Real-time PCR） assay was used to detect messenger ribonucleic acid （mRNA） contents of the natural killer group 2 member D （NKG2D） receptor， ribonucleic acid export-1 （RAE-1）， and γ interferon （IFN-γ） in the tumour tissues of each group. NKG2D， RAE-1， and IFN-γ mRNA in tumour tissues of each group. Immunohistochemistry （IHC） and Western blot were applied to detect the expressions of RAE-1， NKG2D， and IFN-γ in tumour tissues of each group， and Western blot was used to detect the expressions of interleukin-6 （IL-6）， Janus kinase 2 （JAK2）， p-JAK2， signal transducer and activator of transcription 3 （STAT3）， and p-STAT3 in tumour tissues of each group， as well as the protein levels of NKG2D， and RAE-1 in spleen tissues of each group. ResultCompared with that in the model group， the tumour mass decreased in all dose groups of Xiangsha Liu Junzitang， with no statistically significant difference. The tumour volume was reduced （P<0.05， P <0.01）. The pathological morphology was improved. The mRNA contents of NKG2D， RAE-1 and IFN-γ were increased in the medium-dose group （P<0.05， P<0.01）， and the protein expressions of NKG2D， RAE-1， and IFN-γ in tumour tissues were elevated （P<0.05， P<0.01）， and p-JAK2 and p-STAT3 protein expressions were decreased （P<0.05， P<0.01）. In spleen tissues， the protein expressions of NKG2D and RAE-1 in all dose groups of Xiangsha Liu Junzitang were significantly elevated （P<0.01）. Compared with those in the cisplatin group， NKG2D， RAE-1 and IFN-γ mRNA contents were elevated in the middle-dose group of Xiangsha Liu Junzitang， and the difference was not statistically significant. IHC showed that the protein expressions of NKG2D and IFN-γ in the combined group were significantly elevated （P<0.01）， and Western blot results showed that the protein expressions of RAE-1， NKG2D and IFN-γ were elevated （P<0.05， P<0.01）. p-JAK2 and p-STAT3 protein expressions were decreased in the combined group （P<0.05， P<0.01）. NKG2D and RAE-1 protein expressions were significantly increased in spleen tissues of the medium-dose groups and the combined group （P<0.01）. ConclusionXiangsha Liu Junzitang combined with phlegm-removing and detoxifying traditional Chinese medicine can inhibit the growth of tumours in Lewis lung cancer mice by up-regulating the expressions of RAE-1/NKG2D， promoting the activation of NK cells， and inhibiting immune escape， the mechanism of which may be related to down-regulation of the JAK2/STAT3 pathway.
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Lung is susceptible to external disturbance, resulting in a variety of acute and chronic lung diseases. Functionalized nanoparticles as carriers can carry drugs through multiple biological barriers of lung into lung lesions, but there are some problems such as poor targeting and low therapeutic efficiency. As a drug carrier, membrane-coated biomimetic nanoparticles have the characteristics of immune system escape, active targeting, inflammatory chemotaxis and crossing physiological barriers due to the retention of the characteristics of the source cells. Therefore, it has been widely used in the treatment of lung diseases in recent years. In this review, the application of membrane-coated biomimetic nanoparticles in the treatment of lung diseases in the recent years was summarized and classified. Cell membrane sources include erythrocyte membrane, platelet membrane, macrophage membrane, neutrophil membrane, lung epithelial membrane, lung surfactant, endothelial membrane, cancer cell membrane, bacterial membrane, hybrid membrane and so on. The purpose of this review is to provide a new idea for treating lung diseases with membrane-coated biomimetic nanoparticles.
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Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.
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The relationship between tumor metabolism and immunity is complex and diverse. To date, the role of tumor-specific metabolic reprogramming in shaping the specific tumor microenvironment in tumor immunotherapy remains unclear. Lactic acid is the main product of glycolysis, and the aerobic glycolysis of tumor cells causes lactic acid to accumulate in the microenvironment. Recent studies have shown that the accumulation of lactic acid in the tumor microenvironment hinders anti-tumor immunity, especially affects the function, differentiation, and metabolism of immune cells, and participates in tumor immune escape, thus promoting tumor. This article reviews the effects of lactate accumulation in the tumor microenvironment on dendritic cells, T cells, NK cells, tumor-associated macrophages, and myeloid-derived suppressor cells. Targeted intervention of lactate production and efflux by tumor cells is expected to become a new strategy for tumor immunotherapy.
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@#With the deepening of the research on the relationship between oral microbiota and systemic diseases, researchers have found that periodontitis is closely related to diabetes, cardiovascular disease, digestive system disease and other systemic diseases. Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) are common periodontal pathogens, which play a key role in the occurrence and development of periodontitis. At present, it is also found that Fn and Pg are closely related to the occurrence and development of colorectal cancer (CRC). They can affect the occurrence and development of CRC and the therapeutic effect and prognosis of CRC patients through a variety of ways. It can promote tumor cell proliferation by regulating cell division cycle and inhibiting cell apoptosis, inhibit immune cell function to mediate immune escape and tumor metastasis, and create a pro-inflammatory microenvironment suitable for tumor survival. The study of the effect of periodontal pathogens on the occurrence and development of colorectal cancer and its mechanism also allows us to think about new methods, such as vaccine development, immune agents and antibiotic use to better prevent and treat colorectal cancer and improve the prognosis of patients with colorectal cancer.
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Objective: To investigate the effect of long non-coding RNA urothelial carcinoma-associated 1 (UCA1) gene on the proliferation, migration, apoptosis and immune escape of endometrial cancer cells and its molecular mechanism. Methods: Endometrial cancer tissues and adjacent normal tissues of patients with endometrioid adenocarcinoma who underwent total or partial hysterectomy in Henan Provincial People's Hospital from 2017 to 2019 were collected. The expressions of UCA1 and miR-204-5p were detected by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR), and the cell proliferation, migration and apoptosis were detected by cell counting kit 8 (CCK8) method, Transwell method, flow cytometry, and dual-luciferase reporter assay was used to explore the target relationship between UCA1 and miR-204-5p. HEC-1A-sh-NC or HEC-1A-sh-UCA1 cells were co-cultured with peripheral blood mononuclear cells (PBMC) or cytokine-induced killer cells in vitro to explore the role of UCA1 in immune escape. Results: The expression level of UCA1 in endometrial cancer tissue (17.08±0.84) was higher than that in adjacent normal endometrial tissue (3.00±0.37), and the expression level of miR-204-5p (0.98±0.16) was lower than that in adjacent normal endometrial tissue (2.00±0.20, P<0.05). Pearson correlation analysis showed that the expression of miR-204-5p was negatively correlated with the expression of UCA1 (r=-0.330, P=0.030). The expressions of UCA1 and miR-204-5p were associated with the International Federation of Gynecology and Obstetrics stage of endometrial cancer, lymph node metastasis and vascular invasion (P<0.05). The relative ratio of absorbance (0.58±0.11) and the number of cell migration [(199.68±18.44)] in the sh-UCA1 group were lower than those in the sh-NC group (1.24±0.17 and 374.76±24.83), respectively. The apoptosis rate of sh-UCA1 group [(28.64±7.80)%] was higher than that of sh-NC group [(14.27±4.38)%, P<0.05]. After different ratios of effector cells and target cells were cultured, the cell survival rate of HEC-1A-sh-UCA1 group was lower than that of HEC-1A-sh-NC group, and the difference was statistically significant (P<0.05). UCA1 had a binding site for miR-204-5p. The relative ratio of absorbance (1.74±0.08) and the number of cell migration (426.00±18.00) cells in the UCA1+ anti-miR-204-5p group were higher than those in the control group [1.00±0.03 and (284.00±8.00) cells, respectively]. The apoptosis rate of UCA1+ anti-miR-204-5p group [(5.42±0.93)%] was lower than that of control group [(14.82±1.48)%, P<0.05]. HEC-1A-sh-UCA1 cells could induce higher interferon gamma (IFN-γ) expression when co-cultured with PBMC, and the levels of IFN-γ expression in PHA group and PHA+ pre-miR-204-5p group cells were 2.42±0.49 and 1.88±0.26, which were higher than that in the PHA+ pre-NC group (0.85±0.10, P<0.05). When co-cultured with cytokine-induced killer cells (different ratios) in vitro, the HEC-1A-sh-UCA1 group and the HEC-1A-pre-miR-204-5p group had lower survival rates than that in the HEC-1A-pre-miR-204-5p group. In the HEC-1A-pre-NC group, the differences were statistically significant (P<0.05). Conclusion: UCA1/miR-204-5p may play an important role in human endometrial cancer.
Subject(s)
Female , Humans , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , Leukocytes, Mononuclear , Carcinoma, Transitional Cell , Antagomirs , Cell Line, Tumor , Urinary Bladder Neoplasms , Cell Proliferation , Endometrial Neoplasms/genetics , Apoptosis/genetics , Cell Movement/genetics , Gene Expression Regulation, NeoplasticABSTRACT
Epstein-Barr virus(EBV)is a double-stranded DNA herpes virus that is universally susceptible to human populations worldwide.It mainly infects B cells and epithelial cells and has the characteristics of incubation and transformation.The innate immune response is the first line of defense against EBV.In particular, the immune response of type Ⅰ interferons and the direct cell-killing effects of innate cytotoxic lymphocyte are essential for initial control of viral infection and subsequent activation of adaptive immune responses.There is a delicate balance between innate immune response and immune escape of EBV, and the breakdown of the balance is related to the occurrence and prognosis of EBV-related diseases.A better understanding of this balance mechanism will guide the prevention and targeted therapy of EBV-related diseases.This article reviews the role of innate immune cells(epithelial cells, mononuclear/dendritic cells, NK cells, γδT cells, NKT cells)and type Ⅰ interferon in EBV infection and the immune escape mechanism of EBV.
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Glioma is the most common primary intracranial tumor. Despite surgical resection, radiation therapy, chemotherapy, and Tumor Treating Fields, the median survival period is still less than 21 months. In recent years, immunotherapy for glioma has become a research hotspot. The immune microenvironment of glioma plays an important role in immune escape, which is an important means of malignant progression. Exploring the immune escape mechanism of glioma, understanding the progress of immunotherapy, and extending the survival period of patients with glioma as much as possible are the major challenges facing glioma treatment. Therefore, this article reviews the new understanding of the immune system in the central nervous system, immune cells and immune escape in glioma, and immunotherapy for glioma, to help further understand the mechanism of glioma development and provide new ideas for immunotherapy.
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Long non coding RNA(lncRNA)LINC01296 plays a carcinogenic role in different tumor growth,apoptosis,and metastasis,but its mechanism in nasopharyngeal carcinoma is still unclear.The aim of this study is to study the mechanism of knockdown of long non-coding RNA(lncRNA)LINC01296 in inhibiting immune escape of nasopharyngeal carcinoma cells by regulating programmed death ligand-1(PD-L1).In this study,human peripheral blood lymphocytes were isolated and cultured,and then co-cultured with human nasopharyngeal carcinoma cells CNE-2Z,meantime,C57BL/6 mice were injected subcutaneously with CNE-2Z cells to establish a nasopharyngeal carcinoma xenograft model(24 mice).All of them were randomly grouped into control group,lncRNA LINC01296 knockdown group(transfected with lncRNA LINC01296 small interfering RNA(siRNA)),negative control group(transfected with lncRNA LINC01296 siRNA negative control and empty plasmid),and lncRNA LINC01296 knockdown + PD-L1 overexpression group(transfected with lncRNA LINC01296 siRNA and PD-L1 overexpression plasmid).After grouping and transfection,the proportion of activated CD8+ T cells in human peripheral blood lymphocytes was detected by flow cytometry;the killing rate of human peripheral blood lymphocytes to CNE-2Z cells was detected by cell count kit-8 method;the tumor volume of tumor-bearing mice was measured;the CD8 and PD-L1 positive expression in tumor tissue of tumor-bearing mice was measured by immunofluorescence staining;the expression of lncRNA LINC01296 and PD-L1 messenger RNA(mRNA)in CNE-2Z cells and tumor tissues were detected by real-time PCR assay;the expression of PD-L1 protein in CNE-2Z cells and tumor tissues was detected by Western blotting.The results showed that compared with control group,the proportion of activated CD8+ T cells in human peripheral blood lymphocytes,the killing rate of CNE-2Z cells,and the positive proportion of CD8 in tumor tissue of the lncRNA LINC01296 knockdown group increased(P<0.05),the tumor volume and the expression of positive proportion of PD-L1,double positive proportion of CD8 and PD-L1,lncRNA LINC01296,PD-L1 mRNA and protein in CNE-2Z cells and tumor tissue decreased(P<0.05);there was no obvious change in each index of the mice in the negative control group(P>0.05);overexpression of PD-L1 can weaken the effects of lncRNA LINC01296 knocking down on various indicators in CNE-2Z cells and mice.In summary,knockdown of lncRNA LINC01296 can promote the activation and infiltration of CD8+ T cells by down-regulating PD-L1,attenuate the immune escape of nasopharyngeal carcinoma cells,and enhance the lethality of CD8+ T cells.
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Collagen is one of the most abundant proteins in the body and is the main component of the extracellular matrix.Collagen regulates cellular behavior,and its dysregulation can cause a variety of diseases,including cancer.Collagen in tumors is mainly produced by fibroblasts and plays an important role in cancer progression and metastasis.Collagen can act as a prognostic predictor for cancer patients and may be an effective target for the treatment and prevention of tumor progression and metastasis.Anti-tumor drugs targeting collagen and its receptors may be developed in the future.This review focuses on the newly discovered role of collagen in cancer in recent years,specifically the role of collagen in tumor cell dormancy and immune evasion,and the participation of collagen in tumor cell metabolism.
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Chimeric antigen receptor T cell(CAR-T)therapy has produced remarkable results in the treatment of hematological tumors.The BCMA antigen is widely expressed on the surface of multiple myeloma cells and is a suitable,efficient target for CAR-T therapy.BCMA CAR-T cell therapy has a high response rate for relapsed or refractory patients in particular,and CAR-T cells are still detectable in most patients 1 year after infusion.However,drug resistance and disease recurrence remain key problems in clinical management.In this paper,we discuss the response factors and resistance induction mechanism of BCMA CAR-T cell therapy from several perspectives,such as the immune es-cape of multiple myeloma cells,CAR-T product factors,previous treatment regimens,and tumor immune microenvironment inhibition.We also propose possible optimization strategies in order to provide reference for future exploration.
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SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.
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Klebsiella pneumoniae can cause a variety of infectious diseases, especially in immunocompromised population. The emergence of multidrug-resistant hypervirulent Klebsiella pneumoniae has greatly limited the choice of treatment for Klebsiella pneumoniae infection, and the exploration of new treatment strategies is imminent. In the process of infection, there is a complex interaction between the programmed cell death of host cells and the invasion of Klebsiella pneumoniae. This paper mainly reviewed the research progress in several mechanisms of programmed cell death such as pyroptosis, apoptosis, necroptosis and autophagy caused by Klebsiella pneumoniae.