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Supervisor:China Association for Science and Technology

Sponsor:Chinese Society for Immunology, Chinese Anti-Cancer Association

Editor-in-Chief:Xuetao CAO

Issue:monthly
Language:Chinese
ISSN 1007-385X
CN 31-1725/R
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Articles in press have been peer-reviewed and accepted, which are not yet assigned to volumes /issues, but are citable by Digital Object Identifier (DOI).
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Expert Form
Immune checkpoint inhibitor-related adverse events: New exploration and new challenges
BAI Rilan, CUI Jiuwei
2021, 28(5): 419-430.   doi: 10.3872/j.issn.1007-385x.2021.05.001
Abstract(24) FullText HTML(14) PDF(7)
Abstract:
In recent years, immune checkpoint inhibitors (ICIs), by enhancing the killing effect of the human immune system on tumor cells, have obtained significant clinical efficacy in anti-tumor therapy. However, sufficient evidence has shown that immunotherapy can lead to unique immune-related adverse events (irAEs) when activating the immune system, which can affect the efficacy of immunotherapy or discontinue the treatment. In recent years, with the wide development of clinical trials of immunotherapy, more and more attention has been paid to the occurrence, adverse events profiles, as well as the development of effective management approaches of irAEs. Common irAEs include dermatitis and thyroiditis, etc. The use of different types of ICIs, different therapeutic doses or combination therapies can lead to different irAEs profiles, even the use of same ICI on different types of tumors can cause different irAEs profiles. At present, it is believed that the occurrence of irAEs is related to the changes of immune system, including excessive activation of the immune system and the breakdown of autoimmune tolerance, but the specific mechanism is still not very clear. This review integrated the new advances that have been made in recent years in the key theory and understanding of exploring the molecular mechanisms and predictive markers associated with irAEs of ICIs therapy to summarize the occurrence characteristics and molecular mechanisms of irAEs. This review also provide an overview of predictive markers, improvement on management principles, as well as new explorations for the treatment of irAEs.
Guidelines · Consensus
Expert guidance for clinical research of genetically engineered T cells (2021)
The Committee of Quality Control and Research of Cell Therapy, China Quality Association for Pharmaceuticals
2021, 28(5): 431-434.   doi: 10.3872/j.issn.1007-385x.2021.05.002
Abstract(94) FullText HTML(13) PDF(2)
Abstract:
Clinical research on genetically engineered T cells has been carried out in China; however, there is no professional guidance for doctors to manage the treatment in such clinical research. Therefore, the Committee of Quality Control and Research of Cell Therapy, China Quality Association for Pharmaceuticals focuses on the specialty of clinical research of genetically engineered T cells, and organizes experts in the field to integrate the latest research progress and clinical practices, aiming to provide advices and suggestions on the selection of patients, the collection and preparation of cells, the storage and transportation of cells, as well as give recommendations on the clinical treatment before and after infusion and the evaluation of curative effects. After several rounds of discussion and revision, the Expert Guidance for Clinical Research of Genetically Engineered T Cells (2021) is finally formulated. This guidance aims to provide recommendations for clinical researchers and guard the safety and benefits of patients to the largest extent.
Basic Research
Role of G protein-coupled receptor kinase 3 in the proliferation, migration and invasion of oral squamous carcinoma cells and its possible mechanism
ZHANG Han, LUO Qingqiong, ZHU Liping, CHEN Fuxiang
2021, 28(5): 435-442.   doi: 10.3872/j.issn.1007-385x.2021.05.003
Abstract(23) FullText HTML(11) PDF(4)
Abstract:
  Objective:  To investigate the effects of silencing G protein-coupled receptor kinase 3 (GRK3) on the proliferation, migration and invasion of oral squamous cell carcinoma (OSCC) cells and the possible underlying mechanisms.  Methods:  GRK3 expression levels in normal oral tissues and OSCC tissues were analyzed using Oncomine database. RNA interference technology was used to down-regulate GRK3 expression in OSCC cell lines WSU-HN6 and CAL27. The interference efficiency was verified by qPCR. The effects of knockdown of GRK3 on proliferation and apoptosis of OSCC cells were detected by CCK-8 assay and Flow cytometry, respectively; the effects on migration and invasion abilities of OSCC cells were determined by Transwell assay; and the effects on mRNA expression levels of molecules associated with cell cycle, epithelial-mesenchymal transition (EMT), and matrix metallopeptidase (MMP) were determined by qPCR. The changes in protein levels of molecules associated with EMT and MMP were detected using WB assay.  Results:  GRK3 expression level in OSCC tissues was significantly higher than that in normal oral tissues ( P<0.01). After being transfected with si-GRK3, the mRNA expression of GRK3 in OSCC cells was down-regulated by more than 70%. Silencing GRK3 significantly inhibited the proliferation, migration and invasion of OSCC cells (all P<0.01), but had no significant effect on apoptosis (P>0.05). After down-regulation of GRK3, the percentage of OSCC cells in G0/G1 phase was significantly increased (P<0.01); the mRNA expression levels of Cyclin D1, Cyclin D3, CDK2 and CDK4 were decreased (all P<0.05); expression levels of EMT-related proteins (Vimentin, Zeb1 and Slug) were decreased, while E-cadherin was increased (all P<0.05); MMP3 and MMP9 were decreased (all P<0.05), while MMP2 and MMP7 showed no significant changes (all P>0.05).  Conclusion:  GRK3 promotes the proliferation of OSCC cells by regulating cell cycle-related molecules and enhances the migration and invasion through regulating EMT and MMPs.
Effects of TFDP3 knock-out by CRISPR/Cas9 on biological function of prostate cancer PC3 cells
LI Rui, YANG Liu, LI Jinjie, DIAO Yanjun, SU Mingquan, HAO Xiaoke, LIU Jiayun
2021, 28(5): 443-450.   doi: 10.3872/j.issn.1007-385x.2021.05.004
Abstract(11) FullText HTML(10) PDF(4)
Abstract:
  Objective:  CRISPR/Cas9 technology was used to construct a stable transgenic strain of prostate cancer PC3 cells with TFDP3 gene knock-out (KO) to explore the effect of inhibiting TFDP3 expression on cell cycle, apoptosis and invasion of PC3 cells.  Methods:  The sgRNAs were screened by bioinformatics, and the sgRNA-cas9 co-transfection lentivirus with TFDP3 gene knockout was constructed by CRISPR/Cas9 technology. The constructed lentivirus was used to infect PC3 cells, and the stable transgenic strain was screened. Flow cytometry was used to detect the cell cycle distribution and apoptosis of cells in KO group (with TFDP3 KO) and control group. Cell migration and invasion capabilities were further detected by Scratch and Transwell assays.  Results:  Three sgRNAs were obtained through bioinformatics screening. Among them, the sgRNA2 obviously inhibited the prostate cancer gene expression. By using the CRISPR/Cas9 technology, a stable transgenic strain of PC3 prostate cancer cells with low expression of TFDP3 was obtained. The results of Flow cytometry showed that after the expression of TFDP3 gene was inhibited, compared with the control group, the percentage of cells in G0/G1 phase increased while the percentage of cells in G2/M stage decreased in the KO group, and the cell apoptosis rate significantly increased in the KO group (P<0.05); the migration rate of the PC3 cells in the KO group was significantly decreased (24 h migration rate: [44.00±1.60]% vs [65.00±4.40]%, P<0.01); the number of migrated cells in the KO group that passed through the polycarbonate membrane was significantly lower than that of the control group (185.89±11.71 vs 248.33±11.95, P<0.01).  Conclusion:  In this study, a stable transgenic strain of PC3 prostate cancer cell line with TFDP3 gene KO was constructed through CRISPR/Cas9 technology. It was confirmed that after the expression of TFDP3 gene was inhibited, PC3 cell cycle was blocked and the apoptosis rate was increased. Furthermore, the ability of migration and invasion was significantly weakened, suggesting that TFDP3 is a tumor-promoting gene in prostate cancer.
Fibroblast growth factor 13 regulates apoptosis of A549 cells through the ROS/Caspase-3 pathway
LIU Tianyu, TANG Chengcheng, FENG Guang, LEI Jingjing, SUN Chenhao, WANG Ling, LU Hongzhao
2021, 28(5): 451-459.   doi: 10.3872/j.issn.1007-385x.2021.05.005
Abstract(16) FullText HTML(10) PDF(2)
Abstract:
  Objective:  To explore the effect of fibroblast growth factor13 (FGF13) on the generation of reactive oxygen species (ROS) and apoptosis of non-small cell lung cancer A549 cells and its regulatory mechanism.  Methods:  WB was used to detect the background expression of FGF13 in human normal lung epithelial BEAS-2B cells and lung cancer A549 and H460 cells. BEAS-2B and A549 cells were transfected with FGF13 over-expression vector. Two groups of shRNA sequences targeting FGF13 were designed to construct lentivirus interference vector. The packaged lentivirus was used to infect A549 cells. qPCR and WB were used to detect the interference efficiency. DCFH-DA probe combined with fluorescence microplate reader was used to analyze the effect of FGF13 knock-down on the level of ROS in A549 cells. MitoSOX and WB were used to detect mitochondrial ROS levels and nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) protein expression levels. Annexin V-FITC-PI double staining method was used to detect the cell apoptosis and expressions of Caspase-3 and Cleaved Caspase-3 protein.  Results:  FGF13 protein was highly expressed in lung cancer cells compared with BEAS-2B cells (both P<0.05). A549 cell line with over-expression and low-expression of FGF13 were successfully constructed. Over-expression of FGF13 significantly reduced the level of ROS in A549 and BEAS-2B cells (P<0.05), while knockdown of FGF13 significantly increased the level of ROS in A549 cells (P<0.05). Though over-expression and interference of FGF13 had no significant effect on mitochondrial ROS levels in A549 cells, NOX4 protein expression was significantly down-regulated (P<0.05) after FGF13 over-expression and significantly upregulated after FGF13 knockdown (P<0.05), respectively. The interference of FGF13 significantly increased the apoptosis rate (P<0.01) of A549 cells and significantly upregulated the protein expression levels of Caspase-3 and Cleaved Caspase-3 (P<0.05).  Conclusion:  FGF13 regulates ROS production possibly through the NOX family pathway and regulates apoptosis of A549 cells by the ROS/Caspase-3 pathway.
circ_0091579/miR-330-3p/RNF126 axis affects the proliferation, invasion and apoptosis of colorectal cancer LoVo cells
YANG Xingguang, AI Kewei, YANG Jiwu, CHENG Wei, ZHAO Pengju
2021, 28(5): 460-468.   doi: 10.3872/j.issn.1007-385x.2021.05.006
Abstract(33) FullText HTML(18) PDF(1)
Abstract:
  Objective:  To identify the effect of circRNA circ_0091579 on the proliferation, apoptosis and invasion of colorectal cancer (CRC) cells by functioning as a molecular sponge of miR-330-3p and mediating ring finger protein 126 (RNF126).  Methods:  Sixty pairs of cancer tissue and adjacent normal tissue of CRC patients receiving surgical treatment in the First Affiliated Hospital of Dali University from February 2019 to May 2020 were collected. CRC LoVo cells with over-expression or knockdown of circ_0091579 and miR-330-3p were constructed. The expression of circ_0091579, miR-330-3p and RNF126 in CRC tissue and cell lines (HCT116, SW620, CW-2 and LoVo cells) was detected by qPCR. The proliferation, invasion and apoptosis were measured by MTT assay, Transwell assay and Flow cytometry, respectively. The targeting relationship between circ_0091579 and miR-330-3p, miR-330-3p and RNF126 was predicted by bioinformatics tool and verified by Dual luciferase reporter assay and RNA immunoprecipitation experiments.  Results:  In CRC tissues and cell lines, circ_0091579 and RNF126 were both highly expressed, and miR-330-3p was lowly expressed (all P<0.05). Knockdown of circ_0091579 could inhibit the proliferation and invasion, but promote the apoptosis of CRC cells ( P<0.05); however, this effect was reversed by miR-330-3p-inhibitor. Over-expression of miR-330-3p could suppress the ability of proliferation and invasion, but enhance the apoptosis of LoVo cells ( P<0.05), and this effect was rescued after the participation of RNF126. There is a targeting relationship among circ_0091579, miR-330-3p and RNF126.  Conclusion:  circ_0091579 promotes the proliferation and invasion, and inhibits the apoptosis of LoVo cells via miR-330-3p/RNF126 axis.
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Progress of demethylation drug in the treatment of myelodysplastic syndromes
WANG Lin, XU Xiao-ping
2012, 19(5): 550-555.   doi: 10.3872/j.issn.1007-385X.2012.5.018
[Abstract](2159) [PDF 236KB](5)
Abstract:
The current situation and prospect of immunocyte-therapy for tumor
GUO Zhenhong, CAO Xuetao
2016, 23(2): 149-160.   doi: 10.3872/j.issn.1007-385X.2016.02.001
[Abstract](2483) [PDF 441KB](8)
Abstract:
Immunocyte therapy for tumor has drawn a great attention in recent years due to its significant effect. Immunocytes, including T cell, NK cell and DCs, play a key role in immune responses of anti-tumors and immunotherapy of tumors. Among them, the techique of chimeric antigen receptor (CAR) modified-T cell (CAR-T) and inhibitor therapy which reverses CTLA-4 and PD-1/PD-L1 and so on immune checkpoints of tumor immune suppressive function have respectively achieved exciting results in therapies of blood tumors, melanoma and other solid tumors. How to further improve the efficacy, to increase adaptive tumor diseases and to control immune related adverse reactions of the therapy could become the focus of future research. NK cell will also take advantages of CAR technique and inhibitors of immune checkpoints to further strengthen its role in the tumor therapy. How to enhance the curative effect of DCs as the first therapeutic tumor vaccine approved by FDA based on its confirmed safe and non-toxic side effects could become a hot point. In this paper, problems that need to be solved in the field were further analyzed and prospected with combination of recent advances in the immunocyte-therapy for tumor.
Hormonal therapy and overall management of prostate cancer
SHI Fei, XIA Shujie
2018, 25(1): 23-27.   doi: 10.3872/j.issn.1007-385X.2018.01.004
[Abstract](695) [PDF 597KB](2)
Abstract:
Prostate cancer has become one of the most common malignant diseases in Chinese male. Hormonal therapy is an important and effective way to treat prostate cancer (especially advanced prostate cancer); however, some disputes merged from the clinical application are still to be solved. It seems crucial to unify the understanding and implement overall management to get satisfied effect in hormonal therapy of prostate cancer. According to guidelines and clinical trials in both domestic and overseas, we make a summary of series of problems that appeared in hormonal therapy of prostate cancer, such as treatment opportunity, treatment strategy, patients choose, prognosis and follow-up etc.
Preparation of microsphere encapsulating recombinant TIMP-1 adenovirus and its inhibitory effects against hepatocellular carcinoma cells
XIA Dong, WU Bin, LIANG Jian-qun, YU Shao-hong, XU Liang
2010, 17(1): 57-61.   doi: 10.3872/j.issn.1007-385X.2010.1.011
[Abstract](2543) [PDF 664KB](2)
Abstract:
Objective: To prepare polyDLlactidepoly (PELA) microspheres encapsulating recombinant tissue inhibitors of metalloproteinase1 (TIMP1) adenovirus, and to investigate their effects on the proliferation of hepatocellular carcinoma HepG2 cells. Methods:The microsphere was constructed by encapsulating recombinant adenovirus containing TIMP1 in biodegradable PELA. The diameter of the microsphere, quantity of virus encapsulated, loading rate, and releasing kinetics were measured. HepG2 cells were infected with the microspheres; the infection efficiency was examined by fluorescent microscope; and the ultrastructure was observed by TEM. The expression of TIMP1 mRNA in HepG2 cells was examined by semiquantitative RTPCR, and the proliferation of HepG2 cells was detected by MTT assay. Results:The microsphere encapsulating recombinant TIMP1 adenovirus was successfully constructed, with its diameter, entrapment efficiency, and virus loading rate being 1.965, 60.0%, and 10.5×108/mg, respectively. About 60% of the viruses were released within 120 h, and the total releasing time was longer than 240 h. Infection with rAdTIMP1 PELA microsphere efficiently induced TIMP1 expression in HepG2 cells, and significantly inhibited the proliferation of HepG2 cells, with the inhibitory rate being 47%. Conclusion:PELA microsphere encapsulating recombinant TIMP1 adenovirus can markedly inhibit the proliferation of HepG2 cells, which provides an experimental basis for the combining macromolecular chemistry and gene therapy for treatment of hepatocellular carcinoma.
Action mechanism of PD-1/PD-L1 in immune escape of tumor and its clinical application
WANG Yuehua, HU Zhiyuan
2017, 24(7): 784-790.   doi: 10.3872/j.issn.1007-385X.2017.07.015
[Abstract](1435) [PDF 567KB](1)
Abstract:
The development trend of therapeutic monoclonal antibodies for cancer therapy
ZHANG Min, LI Jia, YU Dechao
2017, 24(9): 929-937.   doi: 10.3872/j.issn.1007-385X.2017.09.001
[Abstract](1234) [PDF 849KB](3)
Abstract:
Many advances in the treatment of cancer have been driven by the development of targeted therapies that inhibit oncogenic signaling pathways and tumor-associated angiogenesis, as well as by the therapies that acti-vate immune system to unleash antitumor immunity. Many clinically approved therapies, including monoclonal anti-bodies,antibody-drug conjugates,bispecific antibodies and immune checkpoints, have become important strategies for cancer treatment. Recently, tumor immunotherapy is becoming more and more popular, and antibody medicines acquiring above mentioned immune-modulating effects, such as increasing tumor antigenicity or promoting intratu-moral T cell infiltration, had achieved great clinical benefits; monoclonal antibody medicine in combination with tu-mor immunotherapy, molecular targeted antibody medicine, chemotherapy or small molecular inhibitors and even surgery, will further enlarge the application value of antibody medicines in tumor therapies.
Progress of cancer immunotherapy by chimeric antigen receptor-engineered T cells
QING Fang-yuan, CHEN Ya-ning, HAN Shuang-yin
2012, 19(6): 648-651.   doi: 10.3872/j.issn.1007-385X.2012.6.015
[Abstract](3794) [PDF 266KB](5)
Abstract:
Analysis of present situation and future of cancer immunotherapy from the perspective of tumor microenvironment
YU Yu, CUI Jiuwei
2017, 24(7): 693-699.   doi: 10.3872/j.issn.1007-385X.2017.07.001
[Abstract](1444) [PDF 708KB](5)
Abstract:
The studies of immune checkpoint represented by programmed death 1(PD-1) have pushed cancer im-munotherapy to a climax, which implies that modulating the negative immune regulatory pathway could create an ef-fective munotherapy strategy. Meanwhile, the tumor icroenvironment plays an important role in suppressing or enhancing immune response. Therefore, it will provide new immunotherapy strategy, and make foundation for indi-vidualized precision medicine, based on the mechanism of interation between immune response and tumor microen-vironment. This review summarized the research progress of cancer immunotherapy from the perspective of how the tumor microenvironment affects immune response, and aimed to propose a new strategy for cancer immunotherapy.
Synergistic antitumor effects of immunotherapy and chemotherapy and the underlying mechanisms
Liu Yang, Cao Xuetao
2014, 21(1): 98-103.   doi: 10.3872/j.issn.1007-385X.2014.1.017
[Abstract](2506) [PDF 247KB](2)
Abstract: