1.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy.
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
Humans
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Receptors, Antigen, T-Cell, gamma-delta
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Immunotherapy, Adoptive
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T-Lymphocytes
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Immunotherapy
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Neoplasms/therapy*
2.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
3.γδ T cells: Major advances in basic and clinical research in tumor immunotherapy
Yueqi ZHAO ; Peng DONG ; Wei HE ; Jianmin ZHANG ; Hui CHEN
Chinese Medical Journal 2024;137(1):21-33
γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.
4.Changes in related parameters after secondary preparation of blood components
Min GUO ; Jun CHEN ; Ning YANG ; Miao HE ; Jianmin LI ; Wenjuan YANG
Chinese Journal of Blood Transfusion 2024;37(5):586-590,612
Objective To study the changes in related parameters after secondary preparation of blood components,in order to further improve the quality of blood components.Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced,and the quality was tested.Then,using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation,and the red blood cells were washed through the Haemonetics ACP 215 device,and the quality was tested.The preparation pa-rameters of blood components were observed,compared and optimized.Results Under comparable centrifugation effects of different centrifugation conditions,the quality control items,which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation,such as volume,hemoglobin,hematocrit and re-sidual white blood cells met the relevant national standards.And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards,while vol-ume exceeded the standard by 7-14 mL,which can be operated to the standard range.In addition,the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75%and 99%respectively.Conclusion There is a certain correlation between primary and secondary preparation of blood components,but the relevant parameters of secondary prepa-ration of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards,thus ensuring clinical treatment effect and safety.
5.Screening and genotyping of Mur blood group among voluntary blood donors in the population of Hezhou,Guangxi
Weiquan YUAN ; Shaohua DING ; Jianmin LI ; Xueming WU ; Shengming WEN ; Houquan LIN ; Weisheng HE ; Xi-Aoming LI ; Jiajie ZHANG ; Longming XIAO ; Shengbao DUAN ; Shengwang CHEN
Chinese Journal of Blood Transfusion 2024;37(7):773-778
Objective To screen the distribution frequency of Mur blood group among voluntary blood donors in Hezhou,Guangxi,and further analyze the molecular basis of of Mur antigen positive samples.Methods The Mur pheno-type of voluntary blood donors in Hezhou was serologically screened using microplate method,and the distribution frequency of Mur antigens in different ethnic groups was analyzed.Genetic typing was performed on these positive samples with PCR-SSP method to verify the accuracy of the serological method,and the genetic background was sequenced and analyzed.Re-sults Among 3 298 samples from voluntary blood donors in Hezhou,432(13.10%,432/3 298)were screened positive for Mur antigen,and PCR-SSP genotyping validation showed that all 432 samples were electrophoretic positive.Among them,the proportion of Han blood donors with positive Mur antigen was12.79%(331/2 587),Yao ethnic group was13.25%(64/483),Zhuang ethnic group was 16.51%(36/218),and no statistically significant difference was found in the three groups(P>0.05).Further sequencing results showed that 428 samples were GYP(B-A-B)Mur,also known as GYP.Mur type(12.98%,428/3 298),the other 4 samples were GYP(B-A-B)Bun,also known as GYP.Bun type(0.12%,4/3 298).Conclusion The Mur blood type frequency is high in the voluntary blood donors in Hezhou,Guangxi,and is predominant characterized by GYP.Mur genotype.Due to ethnic integration,no significant difference was noticed in the frequency of Mur blood type distribution between Han,Zhuang and Yao population.Therefore,conducting extensive Mur blood group antigen and antibody testing in Hezhou is of great significance for ensuring clinical blood transfusion safety.
6.Current status of palliative care for patients with unresectable metastatic colorectal cancer in China: a questionnaire-based survey
Feng WANG ; Dongliang CHEN ; Zixian WANG ; Ye HE ; Jin LI ; Suzhan ZHANG ; Gong CHEN ; Jianmin XU ; Xianglin YUAN ; Yanqiao ZHANG ; Ruihua XU
Chinese Journal of Gastrointestinal Surgery 2024;27(7):718-725
Objective:To analyze the current adoption of palliative care by patients with unresectable metastatic colorectal cancer (mCRC) in China.Methods:From 1 March 2023 to 30 June 2023, a questionnaire survey was conducted by random sampling. An exclusive research platform for the Blue Book on Clinical Diagnosis and Treatment of Metastatic Colorectal Cancer. An online questionnaire was sent to medical oncologists (including chief physicians, associate chief physicians, attending physicians and residents) in general hospitals and oncology hospitals in four major regions of East, Central, South and Northeast China. The questionnaire contained 28 questions requesting basic information about doctors, the number of patients with mCRC, the status of treatment from first to fourth line and beyond, points concerning treatment of pain in patients with mCRC, and expectations for the future. A medical team was responsible for the quality control of data collected, whereas statisticians performed the data cleaning and sorting and statistical analysis.Results:A total of 300 clinical questionnaires were collected, including 217 (72%) from doctors in general hospitals and 83 (28%) from doctors in oncology hospitals. Senior physicians (including associate chief physicians and chief physicians) accounted for 65% of the respondents, attending physicians 30%, and residents 5%. Within 3 months (average for each month), 46.4±26.6% patients were diagnosed with recurrent or unresectable mCRC by each physician, 51.6±26.8% of the patients being in cancer hospitals and 44.4±26.3% in general hospitals. One hundred percent of patients receiving first-line treatment received palliative care, as did 80.3% of those receiving second-line treatment, 58.2% of those receiving third-line treatment, and 35.1% of those receiving ≥fourth-line treatment. The primary factor governing selection of first-line treatment was guideline recommendations, whereas comorbidities and the patients' physical status dictated second line to fourth line treatment. Standard first-line treatment was administered to 93.8% of eligible patients, standard second-line treatment to 94.3%; and standard third-line treatment to 73.5%. First-line therapy included targeted therapy in 63.6% of patients and immunotherapy in 2.8%; second-line therapy included targeted therapy in 63.0% of patients and immunotherapy in 2.0%; third-line therapy included targeted therapy in 59.2% of patients and immunotherapy in 2.2%; and fourth-line therapy included targeted therapy in 48.7% of patients and immunotherapy in 3.1%. First-line treatment lasted an average of 9.6 months, second-line treatment 6.7 months, third-line treatment 4.9 months, and fourth-line treatment 3.7 months. More than 70% of the patients maintained a good quality of life after receiving first and second-line treatment and more than 60% of them had ECOG performance scores of 0–1. After receiving third- and fourth-line treatment, 50%–60% of patients maintained a good quality of life and 40%–50% of them maintained ECOG performance scores of 0–1. The survey also revealed that the main deficiencies in treatment were limited effectiveness of third-line treatment, insufficient availability and opportunity for clinical research, popularity of new drugs or new drug combination strategies, and limited channels for participation in multidisciplinary diagnosis and treatment. Clinicians reported looking forward to participating in more clinical research on new drugs, hearing about the experience of experts in the field, and discovery of new targets and new drugs that increased the options for posterior line treatment of colorectal cancer.Conclusions:This report objectively summarizes the current situation, treatment difficulties, and expectations of frontline physicians concerning management of mCRC, thus providing a basis for decision-making and future direction for the diagnosis and research on treatment of mCRC.
7.Effects of icariin-astragaloside IV-puerarin mixture on cognitive function and ferroptosis amino acid metabolism pathway in APP/PS1 HAMP-/-mice
Shan LIU ; Xiaoping HE ; Yan ZHAO ; Jianmin ZHONG ; Yehua ZHANG ; Yiming LIU ; Jiaxuan LI ; Xianhui DONG
Chinese Journal of Pathophysiology 2024;40(3):502-510
AIM:To observe the effect of icariin-astragaloside Ⅳ-puerarin mixture(Yin-Huang-Ge mixture,YHG)on cognitive function and ferroptosis amino acid metabolism pathway in hepcidin(HAMP)knockout APPswe/PS1dE9(APP/PS1 HAMP-/-)mice.METHODS:The mice were divided into 7 groups:negative control(C57BL/6 mice)group,APP/PS1 group,APP/PS1 HAMP-/-group,APP/PS1+YHG group,APP/PS1 HAMP-/-+YHG group,APP/PS1+de-ferasirox(DFX)group,and APP/PS1 HAMP-/-+DFX group,with 6 mice in each group.The YHG and DFX were adminis-tered intragastrically,while the mice in C57 group,APP/PS1 group and APP/PS1 HAMP-/-group were given intragastric administration of distilled water,once a day for 2 months.The iron content in mouse brain tissues was detected by tissue iron kit.The morphological changes of the mitochondria in hippocampal neurons were observed by transmission electron microscopy.Morris water maze was used to detect the learning and memory ability of the mice.The content of neuronal nu-clear antigen(NeuN)in mouse brain tissues was detected by immunofluorescence staining.The expression of glutathione(GSH)in mouse brain tissues was detected by biochemical kit.The expression levels of glutamate-cysteine ligase catalytic subunit(GCLC)and glutamatase 2(GLS2)in mouse brain tissues were detected by Western blot.RESULTS:Compared with C57BL/6 mice,the brain iron content of APP/PS1 mice was significantly increased(P<0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P<0.05),the brain neurons were seri-ously damaged(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P<0.01).Compared with APP/PS1 mice,the brain iron content of APP/PS1 HAMP-/-mice was significantly increased(P<0.01),the mitochondria were seriously damaged,the learning and memory ability was significantly decreased(P<0.05),the brain neurons were seriously damaged(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly decreased(P<0.05).After treatment with YHG and DFX,the brain iron content was significantly decreased(P<0.01),the mitochondrial damage was alleviated,the learning and memory ability was significantly increased(P<0.05),the brain neuron damage was alleviated(P<0.01),and the expression levels of GSH,GCLC and GLS2 were significantly increased(P<0.05).CONCLUSION:The YHG can improve the cognitive function of APP/PS1 HAMP-/-mice,and its mechanism may be related to the regulation of ferroptosis amino acid metabolism and the enhancement of antioxidant capacity.
8.Level of injury first aid skills among parents of preschool children in Dongxihu District
XIA Lin ; HE Jianmin ; NING Jingming ; LI Yilin
Journal of Preventive Medicine 2024;36(8):718-722
Objective:
To investigate the level of injury first aid skills and its influencing factors among parents of preschool children in Dongxihu District, Wuhan City, so as to provide insights into carrying out targeted health education work.
Methods:
Parents of preschool children from kindergarten in Dongxihu District were selected using multi-stage stratified cluster sampling method. Basic information of preschool children, parents' demographic information, and parents' knowledge of injury first aid skills were collected through questionnaires. The level of injury first aid skills among parents was analyzed and its influencing factors were identified using a multivariable logistic regression model.
Results:
A total of 1 148 questionnaires were allocated and 1 131 valid questionnaires were recovered, with an effective recovery rate of 98.52%. The respondents included 242 men (21.40%) and 889 women (78.60%). The parents surveyed were mainly mothers, with 862 accounting for 76.22%. The level of injury first aid skills was 39.43%. Among the individual injury first aid skills, the proportions of mastering the treatment of cardiac arrest and arm fracture were relatively high, which were 94.69% and 94.16%, respectively, while the proportion of mastering the correct steps of cardiopulmonary resuscitation was the lowest, at 31.21%. Multivariable logistic regression analysis showed that the grade of children (middle class, OR=1.374, 95%CI: 1.021-1.847; senior class, OR=1.561, 95%CI: 1.147-2.125), age (30 to 34 years old, OR=1.712, 95%CI: 1.170-2.505), education level (high school/technical secondary school and below, OR=0.664, 95%CI: 0.515-0.857), and having learned injury first aid skills (OR=1.653, 95%CI: 1.284-2.129) were influencing factors of injury first aid skills among parents of preschool children.
Conclusions
The level of injury first aid skills among parents of preschool children is relatively low. The first aid ability of parents whose children are in small classes, older, less educated, and have not learned injury first aid skills should be specifically improved.
9.TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis
Jingyi HAN ; Xue ZHANG ; Menghua CAI ; Feng TIAN ; Yi XU ; Hui CHEN ; Wei HE ; Jianmin ZHANG ; Hui TIAN
Chinese Medical Journal 2024;137(13):1592-1602
Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.
10.Therapeutic effect of CAR-γδT cells targeting at BCMA in multiple myeloma
Yinghui LI ; Yi XU ; Jianmin ZHANG ; Hui CHEN ; Wei HE
Basic & Clinical Medicine 2024;44(6):763-771
Objective To construct chimeric antigen receptors modified γδT cells targeting at BCMA(BCMA CAR-γδT)and to evaluate its efficacy of anti-multiple myeloma in vitro.Methods Lentiviral vectors containing BCMA single-chain variable fragment were constructed and transiently transfected into 293T cells.The expression of foreign genes was verified by fluorescence microscopy and Western blot;the lentivirus was packaged and the virus titer was determined by flow cytometry.Human peripheral blood αβT cells were infected and γδT cells were examined for its infection efficiency;LDH release method was used to detect the cytotoxic activity of BCMA CAR-γδT cells against human multiple myeloma cell lines in vitro,and the difference of cytotoxic activity between CAR-γδT cells and CAR-αβT cells was compared by Incucyte S3 Live-Cell Analysis Instrument.Results Twenty-four hours after BCMA-CAR lentiviral vector was transferred into 293T cells,the expression of exogenous ZsGreen was microscopied by fluorescence microscope;CD3ζ was detected by Western blot,which showed that BCMA-CAR could be success-fully expressed.The lentivirus was packaged,collected and concentrated(virus titer of 2.23×108 Tu/mL).Infected αβT cells and γδT cells from human peripheral blood in MOI=5,and the results of flow cytometry showed that infection efficiency of αβT cells was 59.18%±2.56%,γδT cells was 48.15±9.86%.The cytotoxic activity of CAR-γδT cells against human myeloma cell lines MM1.S,H929 with high expression of BCMA and K562 cells with over-expression of BCMA was higher than that of empty vector control γδ T cells,which were signifi-cantly enhanced(P<0.001),but there was no difference in cell lines negative for BCMA expression;Live-Cell Analysis Instrument results showed that the cytotoxic activity of BCMA CAR-γδT cells and BCMA CAR-αβT cells against H929 in vitro was significantly better than their vector control cells.There was no difference in the cytotoxic activities of BCMA CAR-γδT cells as compared with against BCMA negative cell lines,and so do BCMA CAR-T cells.Conclusions Cytotoxic activity of BCMA CAR-γδT targeting at BCMA in vitro was significantly enhanced,which is expected to serve as a novel allogeneic γδT cell product for cell a-doptive immunotherapy of multiple myeloma.


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