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Volume 29,Issue 7,2022 Table of Contents
2022, 29(7):605-612.
DOI: 10.3872/j.issn.1007-385X.2022.07.001
Abstract:
Emerging cancer immunotherapies achieve robust antitumor responses by activating antigen-specific T cells. Despite the tremendous progresses, many cancer patients respond only partially or not at all to these anticancer therapies. mRNA-lipid nanoparticles (mRNA-LNP) technology can be applied to tumor immunotherapy and is currently being studied in various fields, including therapeutic tumor vaccines, bispecific antibodies, cytokines, costimulatory ligands and receptors and CAR-T cell therapy. The most concentrated research areas are therapeutic cancer vaccines and intratumoral immunotherapy. Therapeutic tumor vaccines use encoding peptides that contain mutations found in the patient’s tumor, creating a personalized tumor vaccine composed of neoantigens specific to the patient's tumor. Intratumoral immunotherapy transforms "cold" tumors with little immune cell infiltration into "hot" tumors with increased immune cell infiltration by delivering mRNA encoding potent immune-stimulatory proteins to promote superior anti-tumor immune response with limited systemic toxicity. Tumor immunotherapy is reinvigorated after the application of mRNA-LNP technology in multiple fields of tumor immunotherapy.
Emerging cancer immunotherapies achieve robust antitumor responses by activating antigen-specific T cells. Despite the tremendous progresses, many cancer patients respond only partially or not at all to these anticancer therapies. mRNA-lipid nanoparticles (mRNA-LNP) technology can be applied to tumor immunotherapy and is currently being studied in various fields, including therapeutic tumor vaccines, bispecific antibodies, cytokines, costimulatory ligands and receptors and CAR-T cell therapy. The most concentrated research areas are therapeutic cancer vaccines and intratumoral immunotherapy. Therapeutic tumor vaccines use encoding peptides that contain mutations found in the patient’s tumor, creating a personalized tumor vaccine composed of neoantigens specific to the patient's tumor. Intratumoral immunotherapy transforms "cold" tumors with little immune cell infiltration into "hot" tumors with increased immune cell infiltration by delivering mRNA encoding potent immune-stimulatory proteins to promote superior anti-tumor immune response with limited systemic toxicity. Tumor immunotherapy is reinvigorated after the application of mRNA-LNP technology in multiple fields of tumor immunotherapy.
2022, 29(7):613-622.
DOI: 10.3872/j.issn.1007-385X.2022.07.002
Abstract:
Gut microbiota, a vast ecosystem in the human body, form an interconnected coexisting relationship with the organism. Thanks to the flourishing development of molecular biotechnology, recent gut microbiomics studies have shown that to a large extent, gut microorganisms influence the occurrence and development of tumors. In addition to the direct role of the microorganisms themselves, they also play a significant part in causing changes in the host's inflammatory immune system and metabolic functions, and these changes also have a certain impact on the subsequent antitumor therapy. Due to the importance of gut microorganisms, the value of microecological agents developed on this basis for clinical application in tumor patients is becoming more and more apparent, and these microecological agents may be complementary to future antitumor therapy. In this paper, we demonstrate the role of gut microorganisms on malignant tumors from four aspects, including the status of gut microorganisms, the mechanism of gut microorganism-related tumor development, the impact on antitumor therapy and the biotherapies based on gut microorganisms, and provide new ideas and insights for the development and application of subsequent clinical treatment models.
Gut microbiota, a vast ecosystem in the human body, form an interconnected coexisting relationship with the organism. Thanks to the flourishing development of molecular biotechnology, recent gut microbiomics studies have shown that to a large extent, gut microorganisms influence the occurrence and development of tumors. In addition to the direct role of the microorganisms themselves, they also play a significant part in causing changes in the host's inflammatory immune system and metabolic functions, and these changes also have a certain impact on the subsequent antitumor therapy. Due to the importance of gut microorganisms, the value of microecological agents developed on this basis for clinical application in tumor patients is becoming more and more apparent, and these microecological agents may be complementary to future antitumor therapy. In this paper, we demonstrate the role of gut microorganisms on malignant tumors from four aspects, including the status of gut microorganisms, the mechanism of gut microorganism-related tumor development, the impact on antitumor therapy and the biotherapies based on gut microorganisms, and provide new ideas and insights for the development and application of subsequent clinical treatment models.
LI Wei
,
ZENG Weijie
,
PENG Hao
,
LIU Can
,
LIU Guanghua
,
XIAO Feidi
,
ZENG Guifang
,
LIANG Xiao
,
CAI Cheguo
,
HU Juanyuan
,
ZHOU Ming
2022, 29(7):623-630.
DOI: 10.3872/j.issn.1007-385X.2022.07.003
Abstract:
Objective: To design and prepare a bi-specific chimeric antigen receptor (CAR)-T cell targeting both CD19 and CD22 antigens on the surface of B lymphocytes and to detect its tumor-killing effects in vitro and in vivo. Methods: Second-generation CAR molecules containing CD19 ScFv (human originated) and CD22 ScFv (CD3ε chain as costimulatory domain) were connected with P2A self-cleaving peptide. The synthesized fragment was packaged into lentivival vector pLTR-CMV-MCS. The lentiviruses were packaged with HEK-293T cells and infected with healthy human T cells to prepare CAR-19-22-T cells. Single targeted second-generation CAR-T cells were constructed with the same CD19 ScFv CAR molecules and CD22 ScFv CAR molecules respectively. Prostate cancer 3M cells expressing luciferase,CD19 and/or CD22 were constructed as target cells. Various CAR-T cells were co-cultured with target cells. Luciferase and ELISA methods were used to detect the target-cell killing ability of each group of CAR-T cells and their cytokine secretion. Mouse leukemia models were constructed by injecting Raji-Luc cells through the tail veins of the mice. Different groups of CAR-T cells were then injected respectively for treatment and the treatment efficacy was evaluated. Results: For CAR-19-22-T cells cultured for 7 days, the expression rates of CAR-19 and CAR-22 were 13.7% and 14.3% respectively.The killing rates of 3M-CD19-Luc, 3M-CD22-Luc and 3M-CD19-CD22-Luc cells by CAR-19-22-T cells at 10∶1 efficiency target ratio were significantly higher than those of T cells [(78.1±14.4)% vs (11.1±4.3)%, (46.7± 10.7)% vs (12.4±2.7)%, (90.5±4.3)% vs (14.3±3.7)%, all P<0.01]. CAR-19-22-T cells co-cultured with 3M-CD19-Luc, 3M-CD22-Luc or 3M-CD19-CD22-Luc target cells secreted significantly lower amounts of IFN-γ, TNF-α and IL-2 than those for CAR-19-T or CAR-22-T (P<0.05 or P<0.01). CAR-19-22-T cells had significantly better treatment efficacy on mice infected with Raji-Luc cells. The survival time of these mice was significantly longer than that of the mice in the T-cell group (P<0.01) and compared with those of the tumor-bearing mice in the CAR-19-T group and CAR-22-T group, was not statistically significant (all P>0.05). Conclusion: Bi-specific CAR-19-22-T cells were successfully designed and prepared, which could effectively kill tumor cells expressing CD19 and/or CD22 antigens and have a significant treatment effect on mouse leukemia model of Raji-Luc cells.
Objective: To design and prepare a bi-specific chimeric antigen receptor (CAR)-T cell targeting both CD19 and CD22 antigens on the surface of B lymphocytes and to detect its tumor-killing effects in vitro and in vivo. Methods: Second-generation CAR molecules containing CD19 ScFv (human originated) and CD22 ScFv (CD3ε chain as costimulatory domain) were connected with P2A self-cleaving peptide. The synthesized fragment was packaged into lentivival vector pLTR-CMV-MCS. The lentiviruses were packaged with HEK-293T cells and infected with healthy human T cells to prepare CAR-19-22-T cells. Single targeted second-generation CAR-T cells were constructed with the same CD19 ScFv CAR molecules and CD22 ScFv CAR molecules respectively. Prostate cancer 3M cells expressing luciferase,CD19 and/or CD22 were constructed as target cells. Various CAR-T cells were co-cultured with target cells. Luciferase and ELISA methods were used to detect the target-cell killing ability of each group of CAR-T cells and their cytokine secretion. Mouse leukemia models were constructed by injecting Raji-Luc cells through the tail veins of the mice. Different groups of CAR-T cells were then injected respectively for treatment and the treatment efficacy was evaluated. Results: For CAR-19-22-T cells cultured for 7 days, the expression rates of CAR-19 and CAR-22 were 13.7% and 14.3% respectively.The killing rates of 3M-CD19-Luc, 3M-CD22-Luc and 3M-CD19-CD22-Luc cells by CAR-19-22-T cells at 10∶1 efficiency target ratio were significantly higher than those of T cells [(78.1±14.4)% vs (11.1±4.3)%, (46.7± 10.7)% vs (12.4±2.7)%, (90.5±4.3)% vs (14.3±3.7)%, all P<0.01]. CAR-19-22-T cells co-cultured with 3M-CD19-Luc, 3M-CD22-Luc or 3M-CD19-CD22-Luc target cells secreted significantly lower amounts of IFN-γ, TNF-α and IL-2 than those for CAR-19-T or CAR-22-T (P<0.05 or P<0.01). CAR-19-22-T cells had significantly better treatment efficacy on mice infected with Raji-Luc cells. The survival time of these mice was significantly longer than that of the mice in the T-cell group (P<0.01) and compared with those of the tumor-bearing mice in the CAR-19-T group and CAR-22-T group, was not statistically significant (all P>0.05). Conclusion: Bi-specific CAR-19-22-T cells were successfully designed and prepared, which could effectively kill tumor cells expressing CD19 and/or CD22 antigens and have a significant treatment effect on mouse leukemia model of Raji-Luc cells.
2022, 29(7):631-638.
DOI: 10.3872/j.issn.1007-385X.2022.07.004
Abstract:
Objective:Toinvestigatethemolecular mechanisms of sorafenib (SR) resistance induced by long non-coding RNA small ubiquitinlike modifier 1 pseudogene 3 (lncRNA SUMO1P3) in hepatocellular carcinoma (HCC). Methods: HCC cells HepG2 were cultured in vitro and acted as the control group. The expression of SUMO1P3 was detected by qPCR in HepG2/SR cells, which was induced by continuously increasing the contact concentration. si-SUMO1P3 and si-NC were transfected into HepG2/SR cells by Lipofectamine. pc-SUMO1P3 and pc-DNA were transfected into HepG2 cells respectively, and then treated with 5 μmol/L SR for 24 hours. qPCR was used to detect the expression levels of SUMO1P3 in the transfected cells. The proliferation, migration, invasion and apoptosis of transfected cells were detected by CCK-8, Transwell assay, and FCM, respectively. Western blotting assay was conducted to detect the expression of cyclin D1,Bcl2,BAX,MMP-2, and MMP-9 in the different cell groups. Results: Sorafenib-resistant HepG2/SR cells were successfully constructed.The expression level of SUMO1P3 in the HepG2/SR cells was significantly higher than that in the HepG2 cells(P<0.01).After SUMO1P3 was knocked outintheHepG2/SRcells, comparedwithinthe si-NC group,inthe si-SUMO1P3 group the expression of SUMO1P3, the proliferation, migration and invasion of cells and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly lower while the percentage of apoptotic cells and the expression of BAX were significantly higher (P<0.05 or P<0.01). After SUMO1P3 was over-expressed in the HepG2 cells, compared with in the pc-DNA group, the proliferation, migration and invasion of cells in the pc-SUMO1P3 group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Similarly, compared with in the pc-DNA+SR group, the proliferation, migration and invasion of HepG2 cells in the pc-SUMO1P3+SR group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Conclusion: lncRNA SUMO1P3 can induce the resistance of HepG2 cells to sorafenib by promoting the proliferation, migration and invasion and inhibiting the apoptosis of HepG2 cells.
Objective:Toinvestigatethemolecular mechanisms of sorafenib (SR) resistance induced by long non-coding RNA small ubiquitinlike modifier 1 pseudogene 3 (lncRNA SUMO1P3) in hepatocellular carcinoma (HCC). Methods: HCC cells HepG2 were cultured in vitro and acted as the control group. The expression of SUMO1P3 was detected by qPCR in HepG2/SR cells, which was induced by continuously increasing the contact concentration. si-SUMO1P3 and si-NC were transfected into HepG2/SR cells by Lipofectamine. pc-SUMO1P3 and pc-DNA were transfected into HepG2 cells respectively, and then treated with 5 μmol/L SR for 24 hours. qPCR was used to detect the expression levels of SUMO1P3 in the transfected cells. The proliferation, migration, invasion and apoptosis of transfected cells were detected by CCK-8, Transwell assay, and FCM, respectively. Western blotting assay was conducted to detect the expression of cyclin D1,Bcl2,BAX,MMP-2, and MMP-9 in the different cell groups. Results: Sorafenib-resistant HepG2/SR cells were successfully constructed.The expression level of SUMO1P3 in the HepG2/SR cells was significantly higher than that in the HepG2 cells(P<0.01).After SUMO1P3 was knocked outintheHepG2/SRcells, comparedwithinthe si-NC group,inthe si-SUMO1P3 group the expression of SUMO1P3, the proliferation, migration and invasion of cells and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly lower while the percentage of apoptotic cells and the expression of BAX were significantly higher (P<0.05 or P<0.01). After SUMO1P3 was over-expressed in the HepG2 cells, compared with in the pc-DNA group, the proliferation, migration and invasion of cells in the pc-SUMO1P3 group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Similarly, compared with in the pc-DNA+SR group, the proliferation, migration and invasion of HepG2 cells in the pc-SUMO1P3+SR group and the protein levels of cyclin D1, Bcl2, MMP-2 and MMP-9 were all significantly higher while the percentage of apoptotic cells and the expression of BAX were significantly lower (P<0.05 or P<0.01). Conclusion: lncRNA SUMO1P3 can induce the resistance of HepG2 cells to sorafenib by promoting the proliferation, migration and invasion and inhibiting the apoptosis of HepG2 cells.
2022, 29(7):639-645.
DOI: 10.3872/j.issn.1007-385X.2022.07.005
Abstract:
Objective: To investigate the effects of miR-1243 on the proliferation and migration of hepatocellular carcinoma HepG2 cells by targeting and regulating the expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) and its molecular mechanisms. Methods: qPCR and WB methods were used to detect the levels of miR-1243 and hnRNPA2B1 mRNA and the expression of hnRNPA2B1, cyclin D1 and matrix metalloproteinase-2 (MMP-2) protein in 40 HCC tissues and adjacent tissues (surgically removed in Shouyi Hospital of Wuhan Third Hospital from January 2019 to August 2021), human normal liver QSG-7701 cells and hepatocellular carcinoma HepG2, Hep3b and Huh-7 cells. Dual-luciferase reporter assay was performed to verify the targeting relationship between miR-1243 and hnRNPA2B1. HepG2 cells were randomly divided into control group (not transfected), miR-NC group (transfected with miR-NC), miR-1243 mimic group (transfected with miR-1243 mimic), miR-1243 mimic+pcDNA3.1 group (transfected with miR-1243 mimic and pcDNA3.1), and miR-1243 mimic+pc-hnRNPA2B1 group (transfected with miR-1243 mimic and pc-hnRNPA2B1) and corresponding transfections were then carried out. CCK-8 method was performed to evaluate the proliferation ability of HepG2 cells in each group after transfection. Scratch healing test was performed to evaluate the migration ability of HepG2 cells, and Western blotting was performed to determine the protein expression levels of hnRNPA2B1, cyclin D1 and matrix metalloproteinase-2 (MMP-2). Results: Compared with adjacent tissues or human normal liver cells QSG-7701, the expression level of miR-1243 in liver cancer tissues and cells was significantly reduced, and the expression levels of hnRNPA2B1 mRNA and protein were significantly increased (all P<0.05). The results of Dual-luciferase experiments showed that miR-1243 and hnRNPA2B1 had a targeting relationship, and miR-1243 targeting negatively regulated the expression of hnRNPA2B1 protein. After miR-1243 mimic transfection,the expression of hnRNPA2B1 protein in HepG2 cells, proliferation ability of cells, scratch healing rate, and the expression of cyclin D1 and MMP-2 proteins were all significantly decreased (all P<0.05); the overexpression of both hnRNPA2B1 and miR-1243 could reverse the inhibitory effects of miR-1243 overexpression on the proliferation and migration of HepG2 cells. Conclusion: miR-1243 inhibits the proliferation and migration of liver cancer cells through targeting the expression of hnRNPA2B1.
Objective: To investigate the effects of miR-1243 on the proliferation and migration of hepatocellular carcinoma HepG2 cells by targeting and regulating the expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) and its molecular mechanisms. Methods: qPCR and WB methods were used to detect the levels of miR-1243 and hnRNPA2B1 mRNA and the expression of hnRNPA2B1, cyclin D1 and matrix metalloproteinase-2 (MMP-2) protein in 40 HCC tissues and adjacent tissues (surgically removed in Shouyi Hospital of Wuhan Third Hospital from January 2019 to August 2021), human normal liver QSG-7701 cells and hepatocellular carcinoma HepG2, Hep3b and Huh-7 cells. Dual-luciferase reporter assay was performed to verify the targeting relationship between miR-1243 and hnRNPA2B1. HepG2 cells were randomly divided into control group (not transfected), miR-NC group (transfected with miR-NC), miR-1243 mimic group (transfected with miR-1243 mimic), miR-1243 mimic+pcDNA3.1 group (transfected with miR-1243 mimic and pcDNA3.1), and miR-1243 mimic+pc-hnRNPA2B1 group (transfected with miR-1243 mimic and pc-hnRNPA2B1) and corresponding transfections were then carried out. CCK-8 method was performed to evaluate the proliferation ability of HepG2 cells in each group after transfection. Scratch healing test was performed to evaluate the migration ability of HepG2 cells, and Western blotting was performed to determine the protein expression levels of hnRNPA2B1, cyclin D1 and matrix metalloproteinase-2 (MMP-2). Results: Compared with adjacent tissues or human normal liver cells QSG-7701, the expression level of miR-1243 in liver cancer tissues and cells was significantly reduced, and the expression levels of hnRNPA2B1 mRNA and protein were significantly increased (all P<0.05). The results of Dual-luciferase experiments showed that miR-1243 and hnRNPA2B1 had a targeting relationship, and miR-1243 targeting negatively regulated the expression of hnRNPA2B1 protein. After miR-1243 mimic transfection,the expression of hnRNPA2B1 protein in HepG2 cells, proliferation ability of cells, scratch healing rate, and the expression of cyclin D1 and MMP-2 proteins were all significantly decreased (all P<0.05); the overexpression of both hnRNPA2B1 and miR-1243 could reverse the inhibitory effects of miR-1243 overexpression on the proliferation and migration of HepG2 cells. Conclusion: miR-1243 inhibits the proliferation and migration of liver cancer cells through targeting the expression of hnRNPA2B1.
DUAN Yuqing
,
XIA Ning
,
JIA Yunlong
,
LYU Wei
,
WANG Yu
,
WANG Jiali
,
WANG Xuexiao
,
LIU Tianxu
,
LIU Lihua
2022, 29(7):646-652.
DOI: 10.3872/j.issn.1007-385X.2022.07.006
Abstract:
Objective: To study the efficacy and safety of PD-1 antibody plus chemotherapy compared with those of antiangiogenic drug plus chemotherapy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes. Methods: We collected data from 141 patients with unresectable stage ⅢB/ⅢC and Ⅳ lung adenocarcinoma with negative driving genes who were treated in the Fourth Hospital of Hebei Medical University from March 2018 to August 2021, and retrospectively studied the efficacy and safety of PD-1 antibody plus chemotherapy and those of antiangiogenic drug plus chemotherapy in frontline clinical application. The primary outcome measure was the progression-free survival (PFS), and the secondary outcome measures were objective response rate (ORR), disease control rate (DCR) and adverse reactions. Results: All of the 141 patients were included in the survival analysis. The median follow-up time was 13.0 months (95% CI: 12.0-14.0). The ORRs of PD-1 antibody plus chemotherapy group (group A) and antiangiogenic drug plus chemotherapy group (group B) were 33.33% and 27.38% respectively; the DCRs of group A and group B were 98.25% and 89.29%respectively, both with no statistical significance. The median PFSs of group A and group B were 8.4 months (95% CI: 7.3-9.9) and 6.9 months (95% CI: 6.1-7.7) respectively with no statistical significance. The results of subgroup analysis showed that the median PFSs of group A were longer than those of group B for stage ⅢB/ⅢC patients and patients with liver or brain metastasis (all P<0.01). The incidence of adverse reactions in group A and group B were 26.32% and 14.29% respectively, and most of the adverse reactions were grade 1-2. Conclusion: Compared with antiangiogenic drug plus chemotherapy, PD-1 antibody plus chemotherapy had the same efficacy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes and the adverse reactions were tolerable. These two therapies could be standard first-line treatments for advanced lung adenocarcinoma with negative driving genes.
Objective: To study the efficacy and safety of PD-1 antibody plus chemotherapy compared with those of antiangiogenic drug plus chemotherapy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes. Methods: We collected data from 141 patients with unresectable stage ⅢB/ⅢC and Ⅳ lung adenocarcinoma with negative driving genes who were treated in the Fourth Hospital of Hebei Medical University from March 2018 to August 2021, and retrospectively studied the efficacy and safety of PD-1 antibody plus chemotherapy and those of antiangiogenic drug plus chemotherapy in frontline clinical application. The primary outcome measure was the progression-free survival (PFS), and the secondary outcome measures were objective response rate (ORR), disease control rate (DCR) and adverse reactions. Results: All of the 141 patients were included in the survival analysis. The median follow-up time was 13.0 months (95% CI: 12.0-14.0). The ORRs of PD-1 antibody plus chemotherapy group (group A) and antiangiogenic drug plus chemotherapy group (group B) were 33.33% and 27.38% respectively; the DCRs of group A and group B were 98.25% and 89.29%respectively, both with no statistical significance. The median PFSs of group A and group B were 8.4 months (95% CI: 7.3-9.9) and 6.9 months (95% CI: 6.1-7.7) respectively with no statistical significance. The results of subgroup analysis showed that the median PFSs of group A were longer than those of group B for stage ⅢB/ⅢC patients and patients with liver or brain metastasis (all P<0.01). The incidence of adverse reactions in group A and group B were 26.32% and 14.29% respectively, and most of the adverse reactions were grade 1-2. Conclusion: Compared with antiangiogenic drug plus chemotherapy, PD-1 antibody plus chemotherapy had the same efficacy in the frontline treatment of advanced lung adenocarcinoma with negative driving genes and the adverse reactions were tolerable. These two therapies could be standard first-line treatments for advanced lung adenocarcinoma with negative driving genes.
2022, 29(7):653-658.
DOI: 10.3872/j.issn.1007-385X.2022.07.007
Abstract:
Objective: To explore the current status, collaboration, hotspots and development trends of domestic and international researches on stimulator of interferon genes (STING) signaling pathway in breast cancer progression from 2009 to 2021. Methods: Using "breast cancer" and "STING" as key words, 122 research papers from core collections were retrieved from Web of Science database and subject to visualization analysis by Citespace software to evaluate the role of STING in regulating breast cancer progression. Results: Since 2016, research papers related to breast cancer and STING have increased rapidly, among which the greatest number of publications came from the United States, with Dana-Farber Cancer Institute ranking the first. Micronuclei produced in DNA strand breakage stimulate the cGAS-STING signaling pathway and can effectively initiate tumor-specific CD8+ T cell anti-tumor immune responses. Key word cluster analysis and analysis of research hotspots and development trends also indicate that anti-tumor immune therapies represented by macrophages are the hot issue in breast cancer and STING related research field. Conclusion: Key molecules in STING signaling pathway will become a new immune target for prevention and treatment of breast cancer.
Objective: To explore the current status, collaboration, hotspots and development trends of domestic and international researches on stimulator of interferon genes (STING) signaling pathway in breast cancer progression from 2009 to 2021. Methods: Using "breast cancer" and "STING" as key words, 122 research papers from core collections were retrieved from Web of Science database and subject to visualization analysis by Citespace software to evaluate the role of STING in regulating breast cancer progression. Results: Since 2016, research papers related to breast cancer and STING have increased rapidly, among which the greatest number of publications came from the United States, with Dana-Farber Cancer Institute ranking the first. Micronuclei produced in DNA strand breakage stimulate the cGAS-STING signaling pathway and can effectively initiate tumor-specific CD8+ T cell anti-tumor immune responses. Key word cluster analysis and analysis of research hotspots and development trends also indicate that anti-tumor immune therapies represented by macrophages are the hot issue in breast cancer and STING related research field. Conclusion: Key molecules in STING signaling pathway will become a new immune target for prevention and treatment of breast cancer.
LAI Mingyao
,
LI Shaoqun
,
LI Xinchen
,
SHAO Yuan
,
YU Jie
,
LI Hainan
,
LI Juan
,
HU Qingjun
,
ZHOU Jiangfen
,
AI Ruyu
,
ZHOU Zhaoming
,
LIN Tao
,
JIN Xin
,
MU Linsen
,
OUYANG Hui
,
LU Ming
,
FAN Xiaohu
,
CAI Linbo
2022, 29(7):659-664.
DOI: 10.3872/j.issn.1007-385X.2022.07.008
Abstract:
Objective: To explore a preparation method for glioblastoma organoid (GBO) derived from patients with glioblastoma (GBM). Methods: The fresh tumor tissue samples of eight GBM patients newly diagnosed and pathologically confirmed in Guangdong 999 Brain Hospital in 2021 were selected, cut into tissue fragments of 0.5-1 mm in size and cultured in a special medium. When the tissue fragments grew into a spherical shape and the diameter reached 1 mm, they were cut into small pieces and passaged. GBOs cultured for more than 2 weeks were selected for paraffin-embedding, sectioned, and then stained with H-E and immunohistochemical staining. Histological and cytological comparisons were performed with parental GBM tissues. Results: Two cases of GBO that could be passaged and cryopreserved were successfully prepared and a GBO biobank was established. The results of H-E staining showed that GBOs retained tissue structure and cell morphology similar to those of the parental GBM tissues. The results of immunohistochemical analysis showed that the expressions of GFAP, OLIG2, Ki67 and ATRX in GBO and parental GBM tissues were basically consistent. Conclusion: GBO can be generated in vitro by trimming patient-derived GBM tissue and culturing it in a suitable medium. The GBO prepared by this method is consistent with the parental GBM tissue at the histological and cytological levels.
Objective: To explore a preparation method for glioblastoma organoid (GBO) derived from patients with glioblastoma (GBM). Methods: The fresh tumor tissue samples of eight GBM patients newly diagnosed and pathologically confirmed in Guangdong 999 Brain Hospital in 2021 were selected, cut into tissue fragments of 0.5-1 mm in size and cultured in a special medium. When the tissue fragments grew into a spherical shape and the diameter reached 1 mm, they were cut into small pieces and passaged. GBOs cultured for more than 2 weeks were selected for paraffin-embedding, sectioned, and then stained with H-E and immunohistochemical staining. Histological and cytological comparisons were performed with parental GBM tissues. Results: Two cases of GBO that could be passaged and cryopreserved were successfully prepared and a GBO biobank was established. The results of H-E staining showed that GBOs retained tissue structure and cell morphology similar to those of the parental GBM tissues. The results of immunohistochemical analysis showed that the expressions of GFAP, OLIG2, Ki67 and ATRX in GBO and parental GBM tissues were basically consistent. Conclusion: GBO can be generated in vitro by trimming patient-derived GBM tissue and culturing it in a suitable medium. The GBO prepared by this method is consistent with the parental GBM tissue at the histological and cytological levels.
2022, 29(7):665-670.
DOI: 10.3872/j.issn.1007-385X.2022.07.009
Abstract:
食管癌是常见的预后最差的恶性肿瘤之一。近年来，微生物参与肿瘤发生与发展、治疗和预防的可能机制引起了广 泛关注。菌群平衡对维持机体的代谢和免疫功能非常重要，微生物与食管癌的发生与发展及治疗密切相关。根据对正常食管、 食管鳞状细胞癌（ESCC）、食管腺癌（EAC）菌群特征的分析表明，某些代表性微生物可以作为食管癌的生物标志物。这些微生物 对消化道细胞、肿瘤、免疫细胞及食管癌微环境具有一定的影响，促进食管癌的发生与发展。越来越多的研究表明，微生物也可 以影响食管癌治疗药物的疗效。基于此影响可提出食管癌微生物治疗的新策略，如改变饮食习惯、使用益生元和益生菌、粪菌移 植（FMT）、使用抗生素调节菌群等，将微生物治疗与现有的抗肿瘤治疗方法相结合，有望提高食管癌的治疗疗效、改善患者的 预后。
食管癌是常见的预后最差的恶性肿瘤之一。近年来，微生物参与肿瘤发生与发展、治疗和预防的可能机制引起了广 泛关注。菌群平衡对维持机体的代谢和免疫功能非常重要，微生物与食管癌的发生与发展及治疗密切相关。根据对正常食管、 食管鳞状细胞癌（ESCC）、食管腺癌（EAC）菌群特征的分析表明，某些代表性微生物可以作为食管癌的生物标志物。这些微生物 对消化道细胞、肿瘤、免疫细胞及食管癌微环境具有一定的影响，促进食管癌的发生与发展。越来越多的研究表明，微生物也可 以影响食管癌治疗药物的疗效。基于此影响可提出食管癌微生物治疗的新策略，如改变饮食习惯、使用益生元和益生菌、粪菌移 植（FMT）、使用抗生素调节菌群等，将微生物治疗与现有的抗肿瘤治疗方法相结合，有望提高食管癌的治疗疗效、改善患者的 预后。
2022, 29(7):671-680.
DOI: 10.3872/j.issn.1007-385X.2022.07.010
Abstract:
头颈部鳞状细胞癌（HNSCC）是最常见的一类异质性恶性肿瘤。超过60%的HNSCC患者在确诊时已处在肿瘤晚期 或转移阶段，针对复发性或转移性HNSCC（R/MHNSCC）患者可选择的治疗方式及其疗效有限。肿瘤免疫治疗是治疗HNSCC的 重要手段之一，尽管免疫治疗持久的反应率较高，但目前只有很低比例的HNSCC患者作出反应，临床上仍存在免疫治疗耐药等 挑战。HNSCC肿瘤微环境（TME）的生物学特征、动态抑制性变化和异质性等特点，在HNSCC的发生与发展、免疫逃逸和治疗耐 药中起重要的作用。在综述中，论述了抗肿瘤免疫细胞以及细胞外成分在HNSCC的TME中的作用及其机制，总结了HNSCC相 关免疫治疗策略，并展望了免疫治疗与放射或化学治疗等传统肿瘤治疗方式组合提高HNSCC个体精准化免疫治疗的疗效。
头颈部鳞状细胞癌（HNSCC）是最常见的一类异质性恶性肿瘤。超过60%的HNSCC患者在确诊时已处在肿瘤晚期 或转移阶段，针对复发性或转移性HNSCC（R/MHNSCC）患者可选择的治疗方式及其疗效有限。肿瘤免疫治疗是治疗HNSCC的 重要手段之一，尽管免疫治疗持久的反应率较高，但目前只有很低比例的HNSCC患者作出反应，临床上仍存在免疫治疗耐药等 挑战。HNSCC肿瘤微环境（TME）的生物学特征、动态抑制性变化和异质性等特点，在HNSCC的发生与发展、免疫逃逸和治疗耐 药中起重要的作用。在综述中，论述了抗肿瘤免疫细胞以及细胞外成分在HNSCC的TME中的作用及其机制，总结了HNSCC相 关免疫治疗策略，并展望了免疫治疗与放射或化学治疗等传统肿瘤治疗方式组合提高HNSCC个体精准化免疫治疗的疗效。
2022, 29(7):681-685.
DOI: 10.3872/j.issn.1007-385X.2022.07.011
Abstract:
紧密连接蛋白claudin 18.2（CLDN18.2）是一种细胞旁紧密连接结构中的膜蛋白，具有维持屏障、细胞旁运输和信号转 导等作用，在正常组织中特异性的表达于胃黏膜上皮细胞，在胃癌的发生与发展中并未丢失，在食管癌和胰腺癌等消化系统恶性 肿瘤中常异位激活并高表达，这使得CLDN18.2成为消化系统恶性肿瘤治疗的一个潜在靶点。目前，针对CLDN18.2的特异性抗 体zolbetuximab在临床试验中取得了显著的成功，有望成为CLDN18.2阳性的消化系统恶性肿瘤的一线治疗方案。此外，靶向 CLDN18.2的个体化免疫治疗还包括单克隆抗体、CAR-T细胞、双克隆抗体和抗体药物偶联物等，但大多数的研究还在临床研究 初始阶段，因此，靶向CLDN18.2的个体化免疫治疗或将是下一个消化系统恶性肿瘤研究的热点。
紧密连接蛋白claudin 18.2（CLDN18.2）是一种细胞旁紧密连接结构中的膜蛋白，具有维持屏障、细胞旁运输和信号转 导等作用，在正常组织中特异性的表达于胃黏膜上皮细胞，在胃癌的发生与发展中并未丢失，在食管癌和胰腺癌等消化系统恶性 肿瘤中常异位激活并高表达，这使得CLDN18.2成为消化系统恶性肿瘤治疗的一个潜在靶点。目前，针对CLDN18.2的特异性抗 体zolbetuximab在临床试验中取得了显著的成功，有望成为CLDN18.2阳性的消化系统恶性肿瘤的一线治疗方案。此外，靶向 CLDN18.2的个体化免疫治疗还包括单克隆抗体、CAR-T细胞、双克隆抗体和抗体药物偶联物等，但大多数的研究还在临床研究 初始阶段，因此，靶向CLDN18.2的个体化免疫治疗或将是下一个消化系统恶性肿瘤研究的热点。
2022, 29(7):686-691.
DOI: 10.3872/j.issn.1007-385X.2022.07.012
Abstract:
分化抗原簇70（CD70）是肿瘤坏死因子受体超家族的成员之一，属于Ⅱ型穿膜糖蛋白。正常组织中CD70仅短暂地表 达在活化的T细胞、B细胞及成熟的树突状细胞中。CD70在多种肿瘤细胞表面高表达，不仅可使肿瘤细胞逃避免疫监视、诱导免 疫细胞凋亡，同时也可以激活部分免疫细胞杀伤肿瘤细胞，这给恶性肿瘤的免疫治疗带来了新的方向。靶向CD70的单克隆抗体 （mAb）、抗体药物偶联物（ADC）以及CAR-T细胞免疫疗法在临床试验中显示出巨大的潜力。对于靶向CD70抗肿瘤药物的认 识，可为其临床应用提供参考和研究依据。
分化抗原簇70（CD70）是肿瘤坏死因子受体超家族的成员之一，属于Ⅱ型穿膜糖蛋白。正常组织中CD70仅短暂地表 达在活化的T细胞、B细胞及成熟的树突状细胞中。CD70在多种肿瘤细胞表面高表达，不仅可使肿瘤细胞逃避免疫监视、诱导免 疫细胞凋亡，同时也可以激活部分免疫细胞杀伤肿瘤细胞，这给恶性肿瘤的免疫治疗带来了新的方向。靶向CD70的单克隆抗体 （mAb）、抗体药物偶联物（ADC）以及CAR-T细胞免疫疗法在临床试验中显示出巨大的潜力。对于靶向CD70抗肿瘤药物的认 识，可为其临床应用提供参考和研究依据。
2022, 29(7):692-697.
DOI: 10.3872/j.issn.1007-385X.2022.07.013
Abstract:
表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）是治疗EGFR基因突变的非小细胞肺癌（NSCLC）的靶向药物，因 其具有精准、高效、安全和使用便捷等优点而备受瞩目。但是，EGFR基因复杂突变（主要包括EGFR基因复合突变与EGFR基因 共突变）会影响NSCLC患者对EGFR-TKI治疗的敏感性。通过降低药物与肿瘤细胞之间的结合力或关键信号转导通路等多种作 用途径，可影响NSCLC患者的近期疗效及预后。根据现有证据分析影响TKI治疗NSCLC疗效的EGFR基因复杂突变类型的研 究发现，大多数EGFR基因复杂突变能够导致TKI疗效不佳，其作用机制可能与突变类型本身对药物的敏感性、介导病理类型更 加恶化或与导致DNA损伤修复障碍等作用相关。因此，提出多靶向药物联合治疗、EGFR-TKI联合化疗或联合血管靶向治疗等 方案，为EGFR基因复杂突变的NSCLC患者提供了新的增强EGFR-TKI疗效的临床治疗策略。
表皮生长因子受体-酪氨酸激酶抑制剂（EGFR-TKI）是治疗EGFR基因突变的非小细胞肺癌（NSCLC）的靶向药物，因 其具有精准、高效、安全和使用便捷等优点而备受瞩目。但是，EGFR基因复杂突变（主要包括EGFR基因复合突变与EGFR基因 共突变）会影响NSCLC患者对EGFR-TKI治疗的敏感性。通过降低药物与肿瘤细胞之间的结合力或关键信号转导通路等多种作 用途径，可影响NSCLC患者的近期疗效及预后。根据现有证据分析影响TKI治疗NSCLC疗效的EGFR基因复杂突变类型的研 究发现，大多数EGFR基因复杂突变能够导致TKI疗效不佳，其作用机制可能与突变类型本身对药物的敏感性、介导病理类型更 加恶化或与导致DNA损伤修复障碍等作用相关。因此，提出多靶向药物联合治疗、EGFR-TKI联合化疗或联合血管靶向治疗等 方案，为EGFR基因复杂突变的NSCLC患者提供了新的增强EGFR-TKI疗效的临床治疗策略。
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
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Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.