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SARS-CoV-2 variants, immune escape, and countermeasures

《医学前沿（英文）》 2022年 第16卷 第2期   页码 196-207 doi: 10.1007/s11684-021-0906-x

摘要： 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.

关键词： SARS-CoV-2     COVID-19     vaccine     immune escape     breakthrough     prevention    

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Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

《医学前沿（英文）》 doi: 10.1007/s11684-023-1017-7

摘要： The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS3) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

关键词： single-cell RNA-seq     glioma     radial glia     primitive oligodendrocyte precursor cell     immune escape    

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Multi-target combinatory strategy to overcome tumor immune escape

《医学前沿（英文）》 2022年 第16卷 第2期   页码 208-215 doi: 10.1007/s11684-022-0922-5

摘要： 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 multi-immune 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.

关键词： immune checkpoints     multi-target     immune escape     immune-related adverse events     combination therapy    

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identification, and clinical application of anti-HBs monoclonal antibody that binds both wild-type and immuneescape mutant HBsAgs

Fanghe LI BM , Chunyan ZHANG MS , Jinghua LIU MS , Xiaoyan ZHANG MS , Bing YAN , Bo ZHANG MS , Yongguo HUANG MS , Jingsong GONG BM , Yan CHEN BM ,

《医学前沿（英文）》 2009年 第3卷 第3期   页码 277-283 doi: 10.1007/s11684-009-0047-0

摘要： Using a standard cellular fusion technique and indirect enzyme-linked immunosorbent assay (ELISA), a hybridoma cell line strain secreting anti-HBs monoclonal antibody (mAb) (defined G6 mAb) was obtained. The cells grew and secreted mAb stably. Antibody titers in the culture supernatant and ascites were 2.048×10 and 4.096×10, respectively. By applying the anti-HBs G6 mAb and horseradish peroxidase (HRP)-labeled goat anti-HBs antibody, we developed a sandwich ELISA (defined G6m ELISA) for detecting both wild-type and immune escape mutant HBsAgs (IEM HBsAg). The assay was performed to detect 17 species of genome recombinant expression HBsAg, including two wild-type species and 15 IEM HBsAg species, which varied in the “a” determinant, in a group of patients infected with hepatitis B virus (HBV). The patients previously had a lower ELISA detection signal [(absorbance of patients/absorbance of normal people (P/N): 1.0―4.5)]. The results demonstrated that the sensitivity of this assay to wild-type HBsAg was no less than 0.125g/L; 12 of 15 IEM HBsAg species (P/N≥2.5) were positive for G6 mAb. Of the positive IEM HBsAg species, two had a low absorbance value at 450nm (), one had an intermediate value and nine had a high value, which was 7.55%(mean), 59.4% and 92.1%―109.4% of the wild-type value, respectively. The two species with low value and the three negative species mutated at the bases 120―124 in the first loop of the HBV “a” determinant. Using the G6 ELISA and two commercial ELISA kits (A and B), 177 patients were tested. The G6 ELISA had a significantly higher detection rate than either commercial ELISAs (19.21% 14.89% and 6.21%, respectively; <0.01, <0.05, respectively).

关键词： hepatitis B virus     gene variation     hepatitis B surface antigen     immune escape     enzyme-linked immunosorbent assay    

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Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

《医学前沿（英文）》 2021年 第15卷 第1期   页码 33-42 doi: 10.1007/s11684-019-0735-3

摘要： Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

关键词： cancer     immunotherapy     immune checkpoint inhibitors     immune-related adverse events     review    

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Research on pedestrian escape route without visibility based on Markov chain model

Xiaoping ZHENG, Lijuan DU, Hongjiang WANG,

《化学科学与工程前沿（英文）》 2010年 第4卷 第3期   页码 283-289 doi: 10.1007/s11705-009-0272-8

摘要： It is a pioneering work to use a Markov chain model to study the pedestrian escape route without visibility. In this paper, based on the Markov chain probability transition matrix, the algorithms with random numbers and the spatial-grid, an escape route in a limited invisible space is obtained. Six pace states (standing, crawling, walking, leaping, jogging, and running) are applied to describe the characteristics of pedestrian behaviors. Besides, eight main direction changes are used to describe the transition characteristic of a pedestrian. At the same time, this paper analyzes the escape route from two views, i.e., pedestrian pace states and directions. The research results show that the Markov chain model is more realistic as a means of studying pedestrian escape routes.

关键词： pioneering     direction     spatial-grid     realistic     transition characteristic    

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Natural killer cells in liver diseases

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 269-279 doi: 10.1007/s11684-018-0621-4

摘要：

The liver has been characterized as a frontline lymphoid organ with complex immunological features such as liver immunity and liver tolerance. Liver tolerance plays an important role in liver diseases including acute inflammation, chronic infection, autoimmune disease, and tumors. The liver contains a large proportion of natural killer (NK) cells, which exhibit heterogeneity in phenotypic and functional characteristics. NK cell activation, well known for its role in the immune surveillance against tumor and pathogen-infected cells, depends on the balance between numerous activating and inhibitory signals. In addition to the innate direct “killer” functions, NK cell activity contributes to regulate innate and adaptive immunity (helper or regulator). Under the setting of liver diseases, NK cells are of great importance for stimulating or inhibiting immune responses, leading to either immune activation or immune tolerance. Here, we focus on the relationship between NK cell biology, such as their phenotypic features and functional diversity, and liver diseases.

关键词： natural killer cell     phenotype     immune activation     immune tolerance     liver diseases    

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Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

《医学前沿（英文）》 2020年 第14卷 第6期   页码 816-819 doi: 10.1007/s11684-020-0823-4

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Heterogeneity of the tumor immune microenvironment and clinical interventions

《医学前沿（英文）》 2023年 第17卷 第4期   页码 617-648 doi: 10.1007/s11684-023-1015-9

摘要： Heterogeneity of the tumor immune microenvironment and clinical interventions

关键词： Heterogeneity tumor immune    

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Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

《医学前沿（英文）》 2018年 第12卷 第2期   页码 229-235 doi: 10.1007/s11684-017-0581-0

摘要：

On May 23, 2017, the US Food and Drug Administration (FDA) approved a treatment for cancer patients with positive microsatellite instability-high (MSI-H) markers or mismatch repair deficient (dMMR) markers. This approach is the first approved tumor treatment using a common biomarker rather than specified tumor locations in the body. FDA previously approved Keytruda for treatment of several types of malignancies, such as metastatic melanoma, metastatic non-small-cell lung cancer, recurrent or metastatic head and neck cancer, refractory Hodgkin lymphoma, and urothelial carcinoma, all of which carry positive programmed death-1/programmed death-ligand 1 biomarkers. Therefore, indications of Keytruda significantly expanded. Several types of malignancies are disclosed by MSI-H status due to dMMR and characterized by increased neoantigen load, which elicits intense host immune response in tumor microenvironment, including portions of colorectal and gastric carcinomas. Currently, biomarker-based patient selection remains a challenge. Pathologists play important roles in evaluating histology and biomarker results and establishing detection methods. Taking gastric cancer as an example, its molecular classification is built on genome abnormalities, but it lacks acceptable clinical characteristics. Pathologists are expected to act as “genetic interpreters” or “genetic translators” and build a link between molecular subtypes with tumor histological features. Subsequently, by using their findings, oncologists will carry out targeted therapy based on molecular classification.

关键词： molecular classification     precision medicine     pembrolizumab     PD-1/PD-L1     MSI-H    

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Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

《医学前沿（英文）》 2014年 第8卷 第1期   页码 1-5 doi: 10.1007/s11684-014-0309-3

摘要：

Hyperthermia is a condition characterized by increased body temperature as a consequence of failed thermoregulation. Hyperthermia occurs when a body produces or absorbs more heat than it dissipates. Hyperthermia also elicits various effects on the physiology of living cells. For instance, fever-range temperature (39β°C to 40β°C) can modulate the activities of immune cells, including antigen-presenting cells, T cells, and natural killer cells. Heat shock temperature (41β°C to 43β°C) can increase the immunogenicity of tumor cells. Cytotoxic temperature (>43β°C) can create an antigen source to induce an anti-tumor immune response. The immunomodulatory effect of hyperthermia has promoted an interest in hyperthermia-aided immunotherapy, particularly against tumors. Hyperthermia has also been used to treat deep fungal, bacterial, and viral skin infections. We conducted a series of open or controlled trials to treat skin human papillomavirus infection by inducing local hyperthermia. More than half of the patients were significantly cured compared with those in the control trial. A series of challenging clinical cases, such as large lesions in pregnant patients or patients with diabetes mellitus, were also successfully and safely managed using the proposed method. However, further studies should be conducted to clarify the underlying mechanisms and promote the clinical applications of hyperthermia.

关键词： hyperthermia     HPV     immune response     virus     tumor    

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Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors

《医学前沿（英文）》 2022年 第16卷 第5期   页码 773-783 doi: 10.1007/s11684-021-0902-1

摘要： The total number of cancer patients who are eligible for and will benefit from immune checkpoint inhibitors (ICIs) in China has not been quantified. This cross-sectional study was conducted to estimate the number of Chinese cancer patients with eligibility and response to ICIs based on the 2015 Chinese cancer statistics and the immune checkpoint inhibitor clinical practice guideline of the Chinese Society of Clinical Oncology. A total of 11 ICIs were recommended for 17 cancer types. The estimated number of eligible patients annually was 1 290 156 (55.18%), which included 888 738 males (60.05%) and 400 468 females (46.67%). The estimated number of responders annually was 448 972 (19.20%), which included 309 023 males (20.88%) and 139 764 females (16.29%). Gastric cancer (n=291 000, 12.45%), non-small-cell lung cancer (n=289 629, 12.39%), and hepatocellular carcinoma (n=277 100, 11.85%) were the top three cancer types with the highest number of eligible patients. Non-small-cell lung cancer (n=180 022, 7.70%), hepatocellular carcinoma (n=75 648, 3.24%), and small-cell lung cancer (n=64 362, 2.75%) were the top three cancer types with the highest number of responders. In conclusion, ICIs provide considerable benefit in Chinese cancer patients under optimal estimation.

关键词： benefit     China     eligibility     immune checkpoint inhibitor     public health    

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Innate immune responses in RNA viral infection

Qian Xu, Yuting Tang, Gang Huang

《医学前沿（英文）》 2021年 第15卷 第3期   页码 333-346 doi: 10.1007/s11684-020-0776-7

摘要： RNA viruses cause a multitude of human diseases, including several pandemic events in the past century. Upon viral invasion, the innate immune system responds rapidly and plays a key role in activating the adaptive immune system. In the innate immune system, the interactions between pathogen-associated molecular patterns and host pattern recognition receptors activate multiple signaling pathways in immune cells and induce the production of pro-inflammatory cytokines and interferons to elicit antiviral responses. Macrophages, dendritic cells, and natural killer cells are the principal innate immune components that exert antiviral activities. In this review, the current understanding of innate immunity contributing to the restriction of RNA viral infections was briefly summarized. Besides the main role of immune cells in combating viral infection, the intercellular transfer of pathogen and host-derived materials and their epigenetic and metabolic interactions associated with innate immunity was discussed. This knowledge provides an enhanced understanding of the innate immune response to RNA viral infections in general and aids in the preparation for the existing and next emerging viral infections.

关键词： innate immune     viral infection     intercellular signaling     metabolic changes     epigenetic changes    

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Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

《医学前沿（英文）》 2019年 第13卷 第1期   页码 24-31 doi: 10.1007/s11684-019-0679-7

摘要： Immune checkpoint inhibitors are a promising strategy in the treatment of cancer, especially advanced types. However, not all patients are responsive to immune checkpoint inhibitors. The response rate depends on the immune microenvironment, tumor mutational burden (TMB), expression level of immune checkpoint proteins, and molecular subtypes of cancers. Along with the Cancer Genome Project, various open access databases, including The Cancer Genome Atlas and Gene Expression Omnibus, provide large volumes of data, which allow researchers to explore responsive or resistant biomarkers of immune checkpoint inhibitors. In this review, we introduced some methodologies on database selection, biomarker screening, current progress of immune checkpoint blockade in solid tumor treatment, possible mechanisms of drug resistance, strategies of overcoming resistance, and indications for immune checkpoint inhibitor therapy.

关键词： immune checkpoint blockade     sensitivity     resistance     data mining    

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Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

《医学前沿（英文）》 2022年 第16卷 第4期   页码 596-609 doi: 10.1007/s11684-021-0868-z

摘要： Sialic acid binding Ig-like lectin 10 (Siglec10) is a member of innate immune checkpoints that inhibits the activation of immune cells through the interaction with its ligand CD24 on tumor cells. Here, by analyzing public databases containing 64 517 patients of 33 cancer types, we found that the expression of Siglec10 was altered in 18 types of cancers and was associated with the clinical outcomes of 11 cancer types. In particular, Siglec10 was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and was inversely associated with the prognosis of the patients. In 131 KIRC patients of our settings, Siglec10 was elevated in the tumor tissues of 83 (63.4%) patients compared with that in their counterpart normal kidney tissues. Moreover, higher level of Siglec10 was associated with advanced disease (stages III and IV) and worse prognosis. Silencing of CD24 in KIRC cells significantly increased the number of Siglec10-expressing macrophages phagocytosing KIRC cells. In addition, luciferase activity assays suggested that Siglec10 was a potential target of the transcription factors c-FOS and GATA1, which were identified by data mining. These results demonstrate that Siglec10 may have important oncogenic functions in KIRC, and represents a novel target for the development of immunotherapies.

关键词： innate immune checkpoint     Siglec10     kidney renal clear cell carcinoma    

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标题 作者 时间 类型 操作

SARS-CoV-2 variants, immune escape, and countermeasures

期刊论文

Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell

期刊论文

Multi-target combinatory strategy to overcome tumor immune escape

期刊论文

identification, and clinical application of anti-HBs monoclonal antibody that binds both wild-type and immuneescape mutant HBsAgs

Fanghe LI BM , Chunyan ZHANG MS , Jinghua LIU MS , Xiaoyan ZHANG MS , Bing YAN , Bo ZHANG MS , Yongguo HUANG MS , Jingsong GONG BM , Yan CHEN BM ,

期刊论文

Advances on immune-related adverse events associated with immune checkpoint inhibitors

Yong Fan, Yan Geng, Lin Shen, Zhuoli Zhang

期刊论文

Research on pedestrian escape route without visibility based on Markov chain model

Xiaoping ZHENG, Lijuan DU, Hongjiang WANG,

期刊论文

Natural killer cells in liver diseases

null

期刊论文

Persistence of humoral and cellular immune response after SARS-CoV-2 infection: opportunities and challenges

Tangchun Wu

期刊论文

Heterogeneity of the tumor immune microenvironment and clinical interventions

期刊论文

Molecular classification and precision therapy of cancer: immune checkpoint inhibitors

null

期刊论文

Hyperthermia on skin immune system and its application in the treatment of human papillomavirus-infected

null

期刊论文

Estimating the number of Chinese cancer patients eligible for and benefit from immune checkpoint inhibitors

期刊论文

Innate immune responses in RNA viral infection

Qian Xu, Yuting Tang, Gang Huang

期刊论文

Screening responsive or resistant biomarkers of immune checkpoint inhibitors based on online databases

Zhen Xiang, Yingyan Yu

期刊论文

Innate immune checkpoint Siglec10 in cancers: mining of comprehensive omics data and validation in patient

期刊论文