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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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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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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.
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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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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
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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Gastric cancer is a common malignant tumor of digestive tract, and its incidence rate and mortality are very high in China. In recent years, immunotherapy represented by immunocheckpoint inhibitors has brought new therapeutic hope for patients with inoperable advanced gastric cancer. Helicobacter pylori infection is closely related to the occurrence and development of gastric cancer. In this review, we summarized the current status of immunotherapy for gastric cancer, the latest research progress on the impact of Helicobacter pylori infection on gastric mucosal immunity and tumor immunotherapy, and summarized the current challenges and future research directions, with a view to providing new ideas for clinical therapy and scientific research.
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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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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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Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer-immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer-immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.
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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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Autophagy and tumor immune escape are important biological mechanisms in the process of tumor cell proliferation and metastasis， involving multiple signaling pathways. The interaction of autophagy and tumor immune escape seriously affects the treatment and prognosis of tumor diseases. However， the correlation between autophagy and tumor immune escape is still not fully elucidated. Recent studies have shown that autophagy can affect the activity of immune cells by regulating the presentation of antigens in tumor cells， the release of cytokines， and the degradation of immune checkpoint proteins， thereby positively or negatively regulating tumor cell immune escape. The activation of autophagy in tumor cells can inhibit the activation of the innate immune sensing pathway of stimulator of interferon genes （STING）-type Ⅰ interferon （IFN-Ⅰ） to inhibit its immunogenicity and cytotoxic T lymphocytes （CTLs）， which promotes tumor immune escape. While autophagy suppression can reduce the infiltration of M2 macrophages， promote the binding of natural killer group 2， member D （NKG2D） to its ligand， and inhibit the recognition of immune checkpoint proteins， thereby exerting an immune-killing effect and inhibiting tumor immune escape. Traditional Chinese medicine （TCM） has unique advantages in anti-tumor research， especially in the unilateral regulation of autophagy or improvement of tumor immunity， but the research based on the regulation of autophagy and tumor immunity by TCM is insufficient. A few studies have shown that Chinese medicine monomers and compounds can exert an anti-tumor effect by regulating cell autophagy and interfering with tumor immune escape， but there is still a lack of systematic elaboration. The present study reviewed correlation between autophagy and tumor immune escape and regulation of autophagy by Chinese medicine to interfere with tumor immune escape to provide new ideas for research on mechanism of TCM against tumor diseases and development of innovative TCM drugs against tumors.
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Immune therapy has become the fourth approach after surgery, chemotherapy, and radiotherapy in cancer treatment. Many immune checkpoints were identified in the last decade since ipilimumab, which is the first immune checkpoint inhibitor to cytotoxic T-lymphocyte associated protein 4, had been approved by the US Food and Drug Administration (FDA) for the treatment of unresectable or metastatic melanoma in 2011. The use of several antibody drugs that target PD1/PD-L1 for various cancer treatments has been approved by the FDA. However, fewer people are benefitting from immune checkpoint inhibitor treatment in solid cancers. Approximately 80% of patients do not respond appropriately because of primary or acquired therapeutic resistance. Along with the characterization of more immune checkpoints, the combinatory treatment of multiimmune checkpoint inhibitors becomes a new option when monotherapy could not receive a good response. In this work, the author focuses on the combination therapy of multiple immune checkpoints (does not include targeted therapy of oncogenes or chemotherapy), introduces the current progression of multiple immune checkpoints and their related inhibitors, and discusses the advantages of combination therapy, as well as the risk of immune-related adverse events.
Subject(s)
Humans , Combined Modality Therapy , Immune Checkpoint Inhibitors , Immunotherapy , Melanoma/drug therapy , Tumor EscapeABSTRACT
Coronavirus disease 2019 (COVID-19) has become a global pandemic disease. SARS-CoV-2 variants have aroused great concern and are expected to continue spreading. Although many countries have promoted roll-out vaccination, the immune barrier has not yet been fully established, indicating that populations remain susceptible to infection. In this review, we summarize the literature on variants of concern and focus on the changes in their transmissibility, pathogenicity, and resistance to the immunity constructed by current vaccines. Furthermore, we analyzed relationships between variants and breakthrough infections, as well as the paradigm of new variants in countries with high vaccination rates. Terminating transmission, continuing to strengthen variant surveillance, and combining nonpharmaceutical intervention measures and vaccines are necessary to control these variants.
Subject(s)
Humans , COVID-19/prevention & control , COVID-19 Vaccines , Pandemics/prevention & control , SARS-CoV-2ABSTRACT
B lymphocyte is an important component of the human immune system and it has a role in the process of the body's specific immunity. In recent years, the research on B cells and tumor immune escape has rapidly progressed. Studies have shown that different types of B cells play different roles in tumor microenvironment through a variety of mechanisms. B cells in the tertiary lymphatic structure promote anti-tumor immunity, while regulatory B cells promote tumor immune escape. Antibody drugs targeting B cells are a promising direction for tumor immunotherapy.
Subject(s)
Humans , B-Lymphocytes/pathology , Immunotherapy , Neoplasms/therapy , Tumor Escape , Tumor MicroenvironmentABSTRACT
Cervical cancer has become a serious threat to women's health worldwide, advanced cervical cancer has limited treatment options. 5-year survival rate is less than 20%, which is a huge challenge for the gynecologic oncology community. Immunotherapy is one of the important treatment for patients with advanced cervical cancer. including immune checkpoint inhibitors, therapeutic vaccines, and periprocedural T-cell immunotherapy, etc. However, immunotherapy resistance makes some patients non-responsive and ineffective. Therefore, there is an urgent need to study and explore the mechanism of immune resistance to improve drug resistance. The present review summarizes the relevant studies on the mechanism of immune resistance in cervical cancer in recent years, mainly divided into factors such as intrinsic tumor and altered external immune environment, and introduces the countermeasures and progresses proposed for immune resistance.
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Osteosarcoma is a malignant tumor with extreme invasiveness and metastasis as well as dismal prognosis. It is critical to rapidly find a unique therapy strategy capable of significantly improving the prognosis of osteosarcoma. Tumor immunotherapy has the potential to reawaken the immune system, restart and sustain the tumor-immune cycle in the body, resulting in the death of tumor cells. CD8+ CTL, CD4+ T cells, NK cells and NKT cells all play critical roles in tumor immunity, while humoral immunity may not only inhibit tumor growth but also enhance it. Researchers have devised various strategies to boost the immune system in recent years based on tumor immune response studies. This paper highlights and examines osteosarcoma immunotherapy from two perspectives: (1) boosting the response of patient's own immune system to the tumor; (2) exogenously improving the patient's immunological function.
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Objective To explore the relation between SLC16A family and clinical characteristics, biological behavior of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods The expression of 14 members of the SLC16A family in LUAD tissues, LUSC tissues and normal tissues in TCGA database was analyzed by Wilcoxon signed rank sum test. Cox regression was used to evaluate the relation between the family and overall survival, progression-free survival of LUAD and LUSC patients. Logistic regression was used to evaluate the relation between the family and TNM, clinical stage of LUAD and LUSC patients. Principal component analysis was used to establish a Score-SLC16As that comprehensively reflected the family in LUAD and LUSC. ROC, Log rank analysis and univariate and multivariate Cox regression analyses were applied to evaluate the diagnostic effect and survival prediction function of Score-SLC16As on LUAD and LUSC respectively. GSEA was used to evaluate the biological significance of Score-SLC16As and CIBERSORT/Immune checkpoint clusters were used to assess the immune status of Score-SLC16As in LUAD and LUSC. Results In LUAD and LUSC, most members of SLC16A family were differentially expressed and significantly correlated with survival prognosis. Score-SLC16As can clearly diagnose LUAD and LUSC, significantly predict survival prognosis, and can be used as an independent risk factor. Score-SLC16As is a risk factor for LUAD but a protective factor for LUSC. Score-SLC16As is closely related to tumor proliferation pathways and immune escape. Conclusion The SLC16A family is closely related to the clinical features and malignant biological behaviors of LUAD and LUSC.
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Ha surgido una nueva variante de preocupación de SARS-CoV-2, cuyos efectos en la evolución de la pandemia parecen inciertos. Sin embargo, ha comenzado a surgir evidencia con respecto al comportamiento viral en cuanto a su transmisibilidad, unión a receptor de la célula hospedadora y escape del sistema inmune. Presentamos una revisión actualizada de los datos existentes en la literatura respecto a los aspectos microbiológicos y epidemiológicos que pueden ayudarnos a comprender las futuras investigaciones en esta variante.(AU)
A new variant of concern for SARS-CoV-2 has emerged, the effects of which on the evolution of the pandemic appear uncertain. However, evidence has begun to emerge regarding viral behavior in terms of its transmissibility, receptor binding on the host cell, and escape from the immune system. We present an updated review of the existing data in the literature regarding the microbiological and epidemiological aspects that can help us understand future research on this variant.(AU)
Subject(s)
Evolution, Molecular , SARS-CoV-2/genetics , Virulence , Behavior , SARS-CoV-2/pathogenicity , COVID-19/epidemiologyABSTRACT
CD47 is a member of the immunoglobulin superfamily. It is expressed on various cells and tissues of human, but it is more expressed on tumor cells, especially in various hematopoietic tumors. The combination of CD47 expressed on tumor cells with signal regulator protein α (SIRPα) on macrophages inhibits the phagocytosis of tumors by macrophages. The reaction can lead to tumor immune escape. CD47 has become a new hot spot in tumor research. This article reviews the correlation between the structure and expression of CD47, CD47-SIRPα, CD47-targeting antibody drugs and lymphoma immunotherapy.