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Volume 29,Issue 10,2022 Table of Contents
2022, 29(10):863-870.
DOI: 10.3872/j.issn.1007-385X.2022.10.001
Abstract:
Cancer immunotherapy has developed at a rapid pace in recent years and has significantly improved the prognosis of many patients with solid tumors. However, not all the patients produce a durable response, and its efficacy is often limited by immunotherapy-related toxicity. Currently, intratumoral immunotherapy is receiving increased attention as a tool for local immunotherapy. In this paper, we first introduce the current research status of immunotherapy in solid tumor and analyze the significant advantages of intratumoral immunotherapy in reducing systemic drug exposure and its adverse effects, enhancing tumor immunogenicity, and overcoming tumor heterogeneity based on the current status of immunotherapy of solid tumors; then, we briefly summarize the currently available drugs for intratumoral immunotherapy and the progress on their application; and finally, we also summarize the challenges and countermeasures faced by intratumoral immunotherapy in terms of efficacy evaluation and implementation, in order to promote and popularize the concept of intratumoral immunotherapy for solid tumors.
Cancer immunotherapy has developed at a rapid pace in recent years and has significantly improved the prognosis of many patients with solid tumors. However, not all the patients produce a durable response, and its efficacy is often limited by immunotherapy-related toxicity. Currently, intratumoral immunotherapy is receiving increased attention as a tool for local immunotherapy. In this paper, we first introduce the current research status of immunotherapy in solid tumor and analyze the significant advantages of intratumoral immunotherapy in reducing systemic drug exposure and its adverse effects, enhancing tumor immunogenicity, and overcoming tumor heterogeneity based on the current status of immunotherapy of solid tumors; then, we briefly summarize the currently available drugs for intratumoral immunotherapy and the progress on their application; and finally, we also summarize the challenges and countermeasures faced by intratumoral immunotherapy in terms of efficacy evaluation and implementation, in order to promote and popularize the concept of intratumoral immunotherapy for solid tumors.
2022, 29(10):871-878.
DOI: 10.3872/j.issn.1007-385X.2022.10.002
Abstract:
Hypoxia and immune escape are two main characteristics of tumors. Hypoxia is an important factor in promoting immune escape of tumors. Recent studies have shown that hypoxia induced lncRNA (HIL) is a key factor mediating hypoxia-promoted immune escape and is a potential marker for the diagnosis, treatment and prognosis evaluation of tumors. HIL has good research and clinical transformation value and is expected to be a potential treatment target of tumor immunotherapy. In this article, we seek to summarize the latest research progress of HIL in the occurrence, development and prognosis of tumors, analyze various mechanisms of HIL inducing tumor immune escape from the perspectives of epithelial-mesenchymal transition, angiogenesis, cancer stem cell formation, glycolysis, immune cell infiltration, immune factor release, interfering with antigen presentation and up-regulation of immune checkpoint expression, and discuss the possibility and clinical significance of a new strategy of combined tumor therapy targeting HILs and immune checkpoints. Moreover, we also analyze the possible solutions to the key issues in the field of HIL, such as identification of universal and tissue-specific key HILs and their mechanism in regulating tumor immunity, clarification of the relationship between HIL and treatment efficacy of tumor immunotherapy, and realization of clinical transformation of new strategies of combined tumor therapy. This review provides a theoretical basis for the tumor treatment strategy of targeting HILs and immune checkpoints.
Hypoxia and immune escape are two main characteristics of tumors. Hypoxia is an important factor in promoting immune escape of tumors. Recent studies have shown that hypoxia induced lncRNA (HIL) is a key factor mediating hypoxia-promoted immune escape and is a potential marker for the diagnosis, treatment and prognosis evaluation of tumors. HIL has good research and clinical transformation value and is expected to be a potential treatment target of tumor immunotherapy. In this article, we seek to summarize the latest research progress of HIL in the occurrence, development and prognosis of tumors, analyze various mechanisms of HIL inducing tumor immune escape from the perspectives of epithelial-mesenchymal transition, angiogenesis, cancer stem cell formation, glycolysis, immune cell infiltration, immune factor release, interfering with antigen presentation and up-regulation of immune checkpoint expression, and discuss the possibility and clinical significance of a new strategy of combined tumor therapy targeting HILs and immune checkpoints. Moreover, we also analyze the possible solutions to the key issues in the field of HIL, such as identification of universal and tissue-specific key HILs and their mechanism in regulating tumor immunity, clarification of the relationship between HIL and treatment efficacy of tumor immunotherapy, and realization of clinical transformation of new strategies of combined tumor therapy. This review provides a theoretical basis for the tumor treatment strategy of targeting HILs and immune checkpoints.
HAN Xiangyang
,
ZHANG Ronghua
,
LI Yufeng
,
SU Jinghui
,
CAO Yumeng
,
HUANG Jinping
,
ZHANG Guangling
,
LI Jingwu
2022, 29(10):879-888.
DOI: 10.3872/j.issn.1007-385X.2022.10.003
Abstract:
Objective: To investigate the effect and mechanism of miR-192-5p targeting ZEB2 (zinc finger E-box binding homeobox 2)on the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) of pancreatic cancer PANC-1 cells. Methods:The TCGA database was used to analyze the expression of miR-192-5p and ZEB2 as well as their correlation in pancreatic cancer tissue.The expression levels of miR-192-5p and ZEB2 were detected by qPCR and WB in human normal pancreatic epithelial HPNE cells and pancreatic cancer PANC-1 cells. PANC-1 cells were transfected with liposome, and divided into miR-192-5p mimic group, Mimic NC group, miR-192-5p inhibitor group, Inhibitor NC group, Mimic NC+pcDNA3.1 group, miR-192-5p mimic+pcDNA3.1 group, andmiR-192-5p mimic+pcDNA3.1-ZEB2 group. The proliferation, colony formation, migration and invasion abilities of transfected PANC-1 cells were detected by CCK-8, colony formation, scratch healing and Transwell experiments, respectively. The expression of ZEB2,E-cadherin and vimentin was detected by qPCR, WB method and double immunofluorescence assay. Bioinformatics was used to predict the target gene of miR-192-5p, and the regulatory effect of miR-192-5p on the target gene was verified by dual luciferase report gene experiment. Results: The expression of ZEB2 in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue (P<0.01), and the expression of miR-192-5p and ZEB2 in pancreatic cancer tissue was inversely correlated (r=-0.419, P<0.01).Compared with normal pancreatic epithelial HPNE cells, the expression level of miR-192-5p was significantly lower while the expression level of ZEB2 protein was higher in pancreatic cancer PANC-1 cells (all P<0.01). Overexpression of miR-192-5p significantly reduced the proliferation, colony formation, migration and invasion ability of PANC-1 cells, upregulated the mRNA and protein expression of E-cadherin, and downregulated the mRNA and protein expression of vimentin and ZEB2, while inhibition of miR-192-5p achieved the opposite results (P<0.05 or P<0.01). miR-192-5p targetedly regulated the expression of ZEB2, and overexpression of ZEB2 could reverse the inhibitory effects of miR-192-5p overexpression on the proliferation, colony formation,migration, invasion and EMT of PANC-1 cells. Conclusion: miR-192-5p regulates the malignant biological behaviors of pancreatic cancer PANC-1 cells by targeting ZEB2.
Objective: To investigate the effect and mechanism of miR-192-5p targeting ZEB2 (zinc finger E-box binding homeobox 2)on the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) of pancreatic cancer PANC-1 cells. Methods:The TCGA database was used to analyze the expression of miR-192-5p and ZEB2 as well as their correlation in pancreatic cancer tissue.The expression levels of miR-192-5p and ZEB2 were detected by qPCR and WB in human normal pancreatic epithelial HPNE cells and pancreatic cancer PANC-1 cells. PANC-1 cells were transfected with liposome, and divided into miR-192-5p mimic group, Mimic NC group, miR-192-5p inhibitor group, Inhibitor NC group, Mimic NC+pcDNA3.1 group, miR-192-5p mimic+pcDNA3.1 group, andmiR-192-5p mimic+pcDNA3.1-ZEB2 group. The proliferation, colony formation, migration and invasion abilities of transfected PANC-1 cells were detected by CCK-8, colony formation, scratch healing and Transwell experiments, respectively. The expression of ZEB2,E-cadherin and vimentin was detected by qPCR, WB method and double immunofluorescence assay. Bioinformatics was used to predict the target gene of miR-192-5p, and the regulatory effect of miR-192-5p on the target gene was verified by dual luciferase report gene experiment. Results: The expression of ZEB2 in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue (P<0.01), and the expression of miR-192-5p and ZEB2 in pancreatic cancer tissue was inversely correlated (r=-0.419, P<0.01).Compared with normal pancreatic epithelial HPNE cells, the expression level of miR-192-5p was significantly lower while the expression level of ZEB2 protein was higher in pancreatic cancer PANC-1 cells (all P<0.01). Overexpression of miR-192-5p significantly reduced the proliferation, colony formation, migration and invasion ability of PANC-1 cells, upregulated the mRNA and protein expression of E-cadherin, and downregulated the mRNA and protein expression of vimentin and ZEB2, while inhibition of miR-192-5p achieved the opposite results (P<0.05 or P<0.01). miR-192-5p targetedly regulated the expression of ZEB2, and overexpression of ZEB2 could reverse the inhibitory effects of miR-192-5p overexpression on the proliferation, colony formation,migration, invasion and EMT of PANC-1 cells. Conclusion: miR-192-5p regulates the malignant biological behaviors of pancreatic cancer PANC-1 cells by targeting ZEB2.
2022, 29(10):889-895.
DOI: 10.3872/j.issn.1007-385X.2022.10.004
Abstract:
Objective: To investigate the effects of miR-515-5p on proliferation, migration and invasion of esophageal cancer (EC) cells and the molecular mechanism. Methods: Cancer tissue specimens from 60 patients with esophageal cancer that surgically resected at the Fourth Hospital of Hebei Medical University from June 2020 to December 2020, esophageal epithelial tissue specimens from 20 healthy adults, as well as esophageal cancer cell lines (TE1, Eca109, KYSE30 and KYSE170) were selected for this study. Quantitative reverse transcription polymerase chain reaction (qPCR) was performed to detect miR-515-5p expression in above mentioned EC tissues and cells. Eca109 cells were transfected with miR-515-5p mimics or its negative controls, and TE1 cells were transfected with miR-515-5p inhibitors or its negative controls. The transfection efficiency was detected by qPCR, and the proliferation, migration and invasion of transfected cells were detected by CCK-8 assay and transwell assay respectively. Bioinformatics tools were used to predict the downstream target genes of miR-515-5p, and HDAC2 (histone deacetylase 2) was verified to be a target gene of miR-515-5p by dual luciferase reporter gene assay. GEPIA and TCGA databases were used to analyze the expression of HDAC2 in EC tissues and its correlation with clinical characteristics of EC patients. Results: miR-515-5p was downregulated in EC tissues and cells (all P<0.01).Over-expression of miR-515-5p inhibited the proliferation, migration and invasion ability of Eca109 cells (P<0.05 or P<0.01), while down-regulation of miR-515-5p enhanced the proliferation, migration and invasion ability of TE1 cells (both P<0.05). Furthermore,HDAC2 was demonstrated to be a target gene of miR-515-5p by dual luciferase reporter gene assay. qPCR and Western blotting results showed that miR-515-5p negatively regulated the mRNA and protein expression of HDAC2. Rescue experiments confirmed that miR-515-5p inhibited the proliferation, migration and invasion ability of esophageal cancer Eca109 cells by targeting HDAC2 (P<0.05 orP<0.01). Conclusion: miR-515-5p affects proliferation, migration and invasion of EC cells by targeting HDAC2.
Objective: To investigate the effects of miR-515-5p on proliferation, migration and invasion of esophageal cancer (EC) cells and the molecular mechanism. Methods: Cancer tissue specimens from 60 patients with esophageal cancer that surgically resected at the Fourth Hospital of Hebei Medical University from June 2020 to December 2020, esophageal epithelial tissue specimens from 20 healthy adults, as well as esophageal cancer cell lines (TE1, Eca109, KYSE30 and KYSE170) were selected for this study. Quantitative reverse transcription polymerase chain reaction (qPCR) was performed to detect miR-515-5p expression in above mentioned EC tissues and cells. Eca109 cells were transfected with miR-515-5p mimics or its negative controls, and TE1 cells were transfected with miR-515-5p inhibitors or its negative controls. The transfection efficiency was detected by qPCR, and the proliferation, migration and invasion of transfected cells were detected by CCK-8 assay and transwell assay respectively. Bioinformatics tools were used to predict the downstream target genes of miR-515-5p, and HDAC2 (histone deacetylase 2) was verified to be a target gene of miR-515-5p by dual luciferase reporter gene assay. GEPIA and TCGA databases were used to analyze the expression of HDAC2 in EC tissues and its correlation with clinical characteristics of EC patients. Results: miR-515-5p was downregulated in EC tissues and cells (all P<0.01).Over-expression of miR-515-5p inhibited the proliferation, migration and invasion ability of Eca109 cells (P<0.05 or P<0.01), while down-regulation of miR-515-5p enhanced the proliferation, migration and invasion ability of TE1 cells (both P<0.05). Furthermore,HDAC2 was demonstrated to be a target gene of miR-515-5p by dual luciferase reporter gene assay. qPCR and Western blotting results showed that miR-515-5p negatively regulated the mRNA and protein expression of HDAC2. Rescue experiments confirmed that miR-515-5p inhibited the proliferation, migration and invasion ability of esophageal cancer Eca109 cells by targeting HDAC2 (P<0.05 orP<0.01). Conclusion: miR-515-5p affects proliferation, migration and invasion of EC cells by targeting HDAC2.
XIONG Li
,
XIONG Rong
,
LIU Yanqun
,
TAN Jingsong
,
ZHANG Ruolan
,
YUE Qiuju
,
SONG Guiqin
,
FENG Gang
,
LIU Kang
2022, 29(10):896-903.
DOI: 10.3872/j.issn.1007-385X.2022.10.005
Abstract:
Objective: To investigate the effects of basonuclin 1 (BNC1) on the proliferation, migration, invasion, cell cycle and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: TThe mRNA expression level of BNC1 in ESCC cells and normal esophageal epithelial cells was detected by qPCR. The protein expression level of BNC1 in cancer and para-cancerous tissues of 10 ESCC patients was detected by immunohistochemical staining. The expression of BNC1 in KYSE-150 and KYSE-30 cells was down-regulated by siRNA, and the effects of BNC1 on cell proliferation, migration, invasion, cell cycle andapoptosis were investigated using CCK-8, scratch healing, Transwell and flow cytometry assays, respectively. The downstream targetgenes of BNC1 were identified by ChIP-seq assay and GEPIA online website date analysis combined with knockdown transcriptome sequencing data after BNC1 knockdown. qPCR was used to verify the expression of target genes after BNC1 knockdown, and dualluciferase reporter gene assay was used to confirm the regulatory effect of BNC1 on the target genes. Results:The mRNA and protein levels of BNC1 were higher in ESCC tissues than in para-cancerous tissues (all P<0.01). Knockdown of BNC1 significantly inhibited the proliferation, migration and invasion of KYSE-150 and KYSE-30 cells (P<0.01 or P<0.01), arrested the cells in G1 phase and promoted the cell apoptosis (all P<0.01). The results of ChIP-seq assay and online website GEPIA date analysis combined with at transcriptome sequencing data indicated after BNC1 knockdown that G protein pathway repressor 1 (GPS1) may be a oncogenic target gene that positively regulated by BNC1. The results of qPCR and dual luciferase reporter gene assay showed that BNC1 had a regulatory effect on GPS1 (P<0.01). Conclusion: BNC1 is highly expressed in ESCC tissues and cells. Interfering with BNC1 significantly inhibits the proliferation, migration and invasion of ESCC cells, arrests cells at G1 phase and promotes cell apoptosis possibly by targeting GPS1 to regulate the malignant biological behaviors of ESCC cells.
Objective: To investigate the effects of basonuclin 1 (BNC1) on the proliferation, migration, invasion, cell cycle and apoptosis of esophageal squamous cell carcinoma (ESCC) cells and its mechanism. Methods: TThe mRNA expression level of BNC1 in ESCC cells and normal esophageal epithelial cells was detected by qPCR. The protein expression level of BNC1 in cancer and para-cancerous tissues of 10 ESCC patients was detected by immunohistochemical staining. The expression of BNC1 in KYSE-150 and KYSE-30 cells was down-regulated by siRNA, and the effects of BNC1 on cell proliferation, migration, invasion, cell cycle andapoptosis were investigated using CCK-8, scratch healing, Transwell and flow cytometry assays, respectively. The downstream targetgenes of BNC1 were identified by ChIP-seq assay and GEPIA online website date analysis combined with knockdown transcriptome sequencing data after BNC1 knockdown. qPCR was used to verify the expression of target genes after BNC1 knockdown, and dualluciferase reporter gene assay was used to confirm the regulatory effect of BNC1 on the target genes. Results:The mRNA and protein levels of BNC1 were higher in ESCC tissues than in para-cancerous tissues (all P<0.01). Knockdown of BNC1 significantly inhibited the proliferation, migration and invasion of KYSE-150 and KYSE-30 cells (P<0.01 or P<0.01), arrested the cells in G1 phase and promoted the cell apoptosis (all P<0.01). The results of ChIP-seq assay and online website GEPIA date analysis combined with at transcriptome sequencing data indicated after BNC1 knockdown that G protein pathway repressor 1 (GPS1) may be a oncogenic target gene that positively regulated by BNC1. The results of qPCR and dual luciferase reporter gene assay showed that BNC1 had a regulatory effect on GPS1 (P<0.01). Conclusion: BNC1 is highly expressed in ESCC tissues and cells. Interfering with BNC1 significantly inhibits the proliferation, migration and invasion of ESCC cells, arrests cells at G1 phase and promotes cell apoptosis possibly by targeting GPS1 to regulate the malignant biological behaviors of ESCC cells.
2022, 29(10):904-910.
DOI: 10.3872/j.issn.1007-385X.2022.10.006
Abstract:
Objective: To analyze the gene expression of coiled-coil domain containing protein 137 (CCDC137) in hepatocellular carcinoma (HCC) tissues and its relationship with clinicopathological features and prognosis of HCC patients, and to explore the effect of CCDC137 knockdown on the proliferation, migration and invasion of MHCC97H cells. Methods: The HCC dataset was downloaded from The Cancer Genome Atlas (TCGA) to obtain the CCDC137 gene expression profile and clinical information of patients. The correlation between the expression level of CCDC137 gene in HCC tissues and the clinicopathological indices and its impact on patients' prognosis were analyzed by bioinformatics method. Gene Set Enrichment Analysis (GSEA) was used to predict the possible pathways regulated by CCDC137 gene in HCC. Kaplan-Meier method and Log-Rank test were used for survival analysis; Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis of patients. The expression of CCDC137 in MHCC97H cells was inhibited by small interfering RNA technology. The mRNA and protein expression levels of CCDC137 in transfected MHCC97H cells as well as its effect on cell proliferation, migration and invasion were observed by qPCR,WB, CCK-8 and Transwell assays, respectively. Results: According to the data of 371 HCC patients retrieved from TCGA database, the expression level of CCDC137 mRNA in tumor tissues was significantly higher than that in the para-cancerous tissues (P<0.01). The high expression of CCDC137 mRNA was significantly correlated with tumor histological grade (OR=0.014), cancer tissue stage (OR=0.007), and T stage (OR=0.047) (all P<0.05). The OS rate of patients with high CCDC137 expression was significantly lower than that of patients with low CCDC137 expression (P<0.05), and multivariate Cox regression analysis suggested that CCDC137 gene could be an independent prognostic factor for HCC patients. GSEA results showed that the samples with high expression of CCDC137 gene were enriched in multiple pathways/gene sets such as base excision repair and spliceosome (P<0.01, FDR<0.05). After knockdown of CCDC137 gene, the proliferation, migration and invasion of MHCC97H cells were significantly decreased (all P<0.01).Conclusion: CCDC137 gene is highly expressed in HCC tissues. The high expression of CCDC137 is related to the occurrence,development and poor prognosis of HCC. Inhibition of CCDC137 gene expression can inhibit the proliferation, migration and invasion of MHCC97H cells.
Objective: To analyze the gene expression of coiled-coil domain containing protein 137 (CCDC137) in hepatocellular carcinoma (HCC) tissues and its relationship with clinicopathological features and prognosis of HCC patients, and to explore the effect of CCDC137 knockdown on the proliferation, migration and invasion of MHCC97H cells. Methods: The HCC dataset was downloaded from The Cancer Genome Atlas (TCGA) to obtain the CCDC137 gene expression profile and clinical information of patients. The correlation between the expression level of CCDC137 gene in HCC tissues and the clinicopathological indices and its impact on patients' prognosis were analyzed by bioinformatics method. Gene Set Enrichment Analysis (GSEA) was used to predict the possible pathways regulated by CCDC137 gene in HCC. Kaplan-Meier method and Log-Rank test were used for survival analysis; Cox proportional hazards regression model was used to analyze the risk factors affecting the prognosis of patients. The expression of CCDC137 in MHCC97H cells was inhibited by small interfering RNA technology. The mRNA and protein expression levels of CCDC137 in transfected MHCC97H cells as well as its effect on cell proliferation, migration and invasion were observed by qPCR,WB, CCK-8 and Transwell assays, respectively. Results: According to the data of 371 HCC patients retrieved from TCGA database, the expression level of CCDC137 mRNA in tumor tissues was significantly higher than that in the para-cancerous tissues (P<0.01). The high expression of CCDC137 mRNA was significantly correlated with tumor histological grade (OR=0.014), cancer tissue stage (OR=0.007), and T stage (OR=0.047) (all P<0.05). The OS rate of patients with high CCDC137 expression was significantly lower than that of patients with low CCDC137 expression (P<0.05), and multivariate Cox regression analysis suggested that CCDC137 gene could be an independent prognostic factor for HCC patients. GSEA results showed that the samples with high expression of CCDC137 gene were enriched in multiple pathways/gene sets such as base excision repair and spliceosome (P<0.01, FDR<0.05). After knockdown of CCDC137 gene, the proliferation, migration and invasion of MHCC97H cells were significantly decreased (all P<0.01).Conclusion: CCDC137 gene is highly expressed in HCC tissues. The high expression of CCDC137 is related to the occurrence,development and poor prognosis of HCC. Inhibition of CCDC137 gene expression can inhibit the proliferation, migration and invasion of MHCC97H cells.
2022, 29(10):911-920.
DOI: 10.3872/j.issn.1007-385X.2022.10.007
Abstract:
Objective: To analyze the association of parathyroid hormone-like hormone (PTHLH) with the prognosis as well as the immune cell infiltration in the tumor microenvironment (TME) of patients with lung squamous cell carcinoma (LSCC). Methods: The expression pattern of PTHLH in pan-cancer was analyzed by UALCAN, TIMER, and cBioPortal databases, and the Kaplan-Meier Plotter database was used to analyze the relationship between the expression of PTHLH in LSCC and the prognosis of patients. The cancer tissues and paracancerous tissues of 24 LSCC patients who underwent surgical resection in the Gansu Cancer Hospital from January 2017 to December 2020 were selected for this study. The mRNA and protein expression levels of PTHLH in LSCC tissues were verified by qPCR and WB, and the expression levels of various chemokines and MHC molecules were detected by qPCR. Then, the correlation between PTHLH expression and immune infiltration in the TME of LSCC was investigated by the TIMER database combined with CIBERSORT deconvolution method.Results: Compared with para-cancerous tissues, the mRNA and protein expression levels of PTHLH were significantly higher in LSCC tissues (both P<0.05). Furthermore, the OS of LSCC patients with high PTHLH expression was significantly shortened (P<0.01). In addition, the expression of PTHLH was closely related to the TME in patients with LSCC (P<0.01). The expression of PTHLH was negatively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils and dendritic cells (r=-0.142, -0.123, -0.224, -0.166,-0.213, all P<0.01). Overexpression of PTHLH inhibited the expression of chemokines and MHC molecules, thereby inhibiting inflammatory responses, immune infiltration, anti-tumor immune responses, etc. Additionally, the expression of PTHLH was negatively correlated with the levels of immune checkpoint molecules CTLA-4, PDCD1 and TIGIT (r=-0.340, -0.441, -0.38, all P<0.01). Conclusion: PTHLH is associated with tumor immunosuppression and is expected to serve as a potential biomarker for predicting immunotherapy effect and prognosis in patients with LSCC.
Objective: To analyze the association of parathyroid hormone-like hormone (PTHLH) with the prognosis as well as the immune cell infiltration in the tumor microenvironment (TME) of patients with lung squamous cell carcinoma (LSCC). Methods: The expression pattern of PTHLH in pan-cancer was analyzed by UALCAN, TIMER, and cBioPortal databases, and the Kaplan-Meier Plotter database was used to analyze the relationship between the expression of PTHLH in LSCC and the prognosis of patients. The cancer tissues and paracancerous tissues of 24 LSCC patients who underwent surgical resection in the Gansu Cancer Hospital from January 2017 to December 2020 were selected for this study. The mRNA and protein expression levels of PTHLH in LSCC tissues were verified by qPCR and WB, and the expression levels of various chemokines and MHC molecules were detected by qPCR. Then, the correlation between PTHLH expression and immune infiltration in the TME of LSCC was investigated by the TIMER database combined with CIBERSORT deconvolution method.Results: Compared with para-cancerous tissues, the mRNA and protein expression levels of PTHLH were significantly higher in LSCC tissues (both P<0.05). Furthermore, the OS of LSCC patients with high PTHLH expression was significantly shortened (P<0.01). In addition, the expression of PTHLH was closely related to the TME in patients with LSCC (P<0.01). The expression of PTHLH was negatively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils and dendritic cells (r=-0.142, -0.123, -0.224, -0.166,-0.213, all P<0.01). Overexpression of PTHLH inhibited the expression of chemokines and MHC molecules, thereby inhibiting inflammatory responses, immune infiltration, anti-tumor immune responses, etc. Additionally, the expression of PTHLH was negatively correlated with the levels of immune checkpoint molecules CTLA-4, PDCD1 and TIGIT (r=-0.340, -0.441, -0.38, all P<0.01). Conclusion: PTHLH is associated with tumor immunosuppression and is expected to serve as a potential biomarker for predicting immunotherapy effect and prognosis in patients with LSCC.
8 Effects of uncoupling protein 2 on prognosis and immune microenvironment of skin cutaneous melanoma
2022, 29(10):921-929.
DOI: 10.3872/j.issn.1007-385X.2022.10.008
Abstract:
Objective: To investigate the prognostic value of uncoupling protein 2 (UCP2) expression in skin cutaneous melanoma (SKCM) and its relationship with tumor infiltrating immune cells (TICs). Methods: GEPIA online dataset was used to explore the differential expression of UCP2 between SKCM and normal skin tissues, and the correlation of UCP with the prognosis of SKCM was further investigated. HPA dataset was used to analyze the UCP2 expression in single cell of normal skin. TISCH was used to analyze the expression of UCP2 in SKCM at single-cell level. TIMER was used to analyze the correlation between the expression of UCP2 and the main immune cells and their markers in the tumor microenvironment (TME) of SKCM, Primary-SKCM and Metastasis-SKCM.Results: UCP2 was highly expressed in SKCM tissues (P<0.05). Higher UCP2 expression were significantly associated with longer overall survival (OS) and disease-free survival (DFS) of SKCM patients (all P<0.05). Single cell analysis of normal skin and SKCM skin showed that there was a certain positive correlation between UCP2 expression and cellular immune cell subsets and that UCP2 was closely related to 5 immune routes (chemokines, receptors, histocompatibility complexes, immunosuppressants and immune activators) (all P<0.05). The subset analysis showed that high UCP2 expression was closely associated with the high OS rate of SKCM and metastatic SKCM patients (all P<0.05). There was a significant positive correlation between UCP2 expression and TICs in the TME of overall SKCM patients, primary SKCM patients and metastatic SKCM patients (all P<0.05), however, the correlation was relatively low in primary SKCM patients. At the same time, the expression of UCP2 was positively correlated with TME immune cell markers in the three groups of SKCM patients. Conclusion: UCP2 is highly expressed in SKCM tissues and positively correlates with TICs in SKCM, which is an important regulatory factor of TME and closely related to the prognosis of SKCM patients.
Objective: To investigate the prognostic value of uncoupling protein 2 (UCP2) expression in skin cutaneous melanoma (SKCM) and its relationship with tumor infiltrating immune cells (TICs). Methods: GEPIA online dataset was used to explore the differential expression of UCP2 between SKCM and normal skin tissues, and the correlation of UCP with the prognosis of SKCM was further investigated. HPA dataset was used to analyze the UCP2 expression in single cell of normal skin. TISCH was used to analyze the expression of UCP2 in SKCM at single-cell level. TIMER was used to analyze the correlation between the expression of UCP2 and the main immune cells and their markers in the tumor microenvironment (TME) of SKCM, Primary-SKCM and Metastasis-SKCM.Results: UCP2 was highly expressed in SKCM tissues (P<0.05). Higher UCP2 expression were significantly associated with longer overall survival (OS) and disease-free survival (DFS) of SKCM patients (all P<0.05). Single cell analysis of normal skin and SKCM skin showed that there was a certain positive correlation between UCP2 expression and cellular immune cell subsets and that UCP2 was closely related to 5 immune routes (chemokines, receptors, histocompatibility complexes, immunosuppressants and immune activators) (all P<0.05). The subset analysis showed that high UCP2 expression was closely associated with the high OS rate of SKCM and metastatic SKCM patients (all P<0.05). There was a significant positive correlation between UCP2 expression and TICs in the TME of overall SKCM patients, primary SKCM patients and metastatic SKCM patients (all P<0.05), however, the correlation was relatively low in primary SKCM patients. At the same time, the expression of UCP2 was positively correlated with TME immune cell markers in the three groups of SKCM patients. Conclusion: UCP2 is highly expressed in SKCM tissues and positively correlates with TICs in SKCM, which is an important regulatory factor of TME and closely related to the prognosis of SKCM patients.
2022, 29(10):930-936.
DOI: 10.3872/j.issn.1007-385X.2022.10.009
Abstract:
趋化因子是免疫系统的重要组成部分，趋化因子CX3CL1因其独特的分子结构和双重的存在形式与其受体CX3CR1 共同影响免疫细胞的募集和归巢，参与多种肿瘤发生和肿瘤免疫过程。趋化因子受体CX3CR1响应CX3CL1的趋化作用。同 时，CX3CR1的表达指示CD8+ T细胞的效应分化状态，CX3CR1+ CD8+ T细胞具有细胞毒性和抗原特异性。在肿瘤微环境中，相比 CX3CR1- CD8+ T细胞，CX3CR1+ CD8+ T细胞表面的共抑制分子表达少、杀伤功能活跃。因此，CX3CR1对于CD8+ T细胞等淋巴 细胞的多重意义使其在肿瘤的细胞免疫治疗，如CAR-T细胞治疗中具有应用前景。在肾细胞癌、黑色素瘤和非小细胞肺癌的 PD-1靶向治疗中，外周血CX3CR1+ CD8+ T细胞的占比与疗效正相关，提示CX3CR1也是早期预测免疫治疗疗效的分子标志物。 尽管CX3CR1+ CD8+ T细胞功能活跃，但此群细胞处于终末分化状态，增殖能力和记忆效应差，不具有长久的保护作用。如何使 CAR-T 细胞在体内维持抗肿瘤作用一直是研究者积极探索的方向，也是将 CX3CR1 应用于 CAR-T 细胞免疫治疗需要克服的 难关。
趋化因子是免疫系统的重要组成部分，趋化因子CX3CL1因其独特的分子结构和双重的存在形式与其受体CX3CR1 共同影响免疫细胞的募集和归巢，参与多种肿瘤发生和肿瘤免疫过程。趋化因子受体CX3CR1响应CX3CL1的趋化作用。同 时，CX3CR1的表达指示CD8+ T细胞的效应分化状态，CX3CR1+ CD8+ T细胞具有细胞毒性和抗原特异性。在肿瘤微环境中，相比 CX3CR1- CD8+ T细胞，CX3CR1+ CD8+ T细胞表面的共抑制分子表达少、杀伤功能活跃。因此，CX3CR1对于CD8+ T细胞等淋巴 细胞的多重意义使其在肿瘤的细胞免疫治疗，如CAR-T细胞治疗中具有应用前景。在肾细胞癌、黑色素瘤和非小细胞肺癌的 PD-1靶向治疗中，外周血CX3CR1+ CD8+ T细胞的占比与疗效正相关，提示CX3CR1也是早期预测免疫治疗疗效的分子标志物。 尽管CX3CR1+ CD8+ T细胞功能活跃，但此群细胞处于终末分化状态，增殖能力和记忆效应差，不具有长久的保护作用。如何使 CAR-T 细胞在体内维持抗肿瘤作用一直是研究者积极探索的方向，也是将 CX3CR1 应用于 CAR-T 细胞免疫治疗需要克服的 难关。
2022, 29(10):937-943.
DOI: 10.3872/j.issn.1007-385X.2022.10.010
Abstract:
间充质干细胞来源的外泌体（MSC-Exo）是由MSC分泌的一类膜泡状物质，与其他细胞来源的Exo相比，MSC-Exo在 成分和功能上有其独特性。MSC-Exo对肿瘤的作用十分复杂且具有双向性，包括肿瘤生长、转移和侵袭、血管生成和耐药等多个 方面，既可促进肿瘤的生长与转移，也可抑制肿瘤的发生和发展。因此，基于MSC-Exo对肿瘤的影响及其机制，设计相关的肿瘤 治疗策略和方案已经成为新的研究方向。本文综述了MSC-Exo的成分与特征、对肿瘤的促进或抑制作用及其机制、作为通讯介 质或药物载体或类细胞治疗在肿瘤治疗中的应用，以及在临床应用中面临的规模化制备难、质量控制难等挑战。
间充质干细胞来源的外泌体（MSC-Exo）是由MSC分泌的一类膜泡状物质，与其他细胞来源的Exo相比，MSC-Exo在 成分和功能上有其独特性。MSC-Exo对肿瘤的作用十分复杂且具有双向性，包括肿瘤生长、转移和侵袭、血管生成和耐药等多个 方面，既可促进肿瘤的生长与转移，也可抑制肿瘤的发生和发展。因此，基于MSC-Exo对肿瘤的影响及其机制，设计相关的肿瘤 治疗策略和方案已经成为新的研究方向。本文综述了MSC-Exo的成分与特征、对肿瘤的促进或抑制作用及其机制、作为通讯介 质或药物载体或类细胞治疗在肿瘤治疗中的应用，以及在临床应用中面临的规模化制备难、质量控制难等挑战。
2022, 29(10):944-949.
DOI: 10.3872/j.issn.1007-385X.2022.10.011
Abstract:
铁死亡是一种近年来发现的与凋亡和坏死及自噬不同的程序性细胞死亡方式，其主要发生机制是在二价铁或脂氧合 酶的作用下，催化细胞中高表达的不饱和脂肪酸发生脂质过氧化，从而诱导细胞死亡。铁死亡参与了多种疾病的发生，如肿瘤、 类风湿性关节炎、神经退行性疾病、缺血再灌注和心脏相关疾病等。肺癌是世界上致死率最高的恶性肿瘤，其治疗策略在不断更 新。近年来，越来越多的研究结果显示，铁死亡与非小细胞肺癌（NSCLC）之间有着紧密的联系。一些在NSCLC的发生发展和治 疗中起重要调节作用的分子（如KRAS、TP53、EGFR等），同样在铁死亡的发生中也发挥作用。此外，在NSCLC中，铁死亡与化学 治疗、放射治疗及免疫治疗也有着密切联系，一些临床前研究证实铁死亡可作为一种“催化剂”，与上述治疗方式联合应用可明显 增强治疗效果，为NSCLC的治疗提供了新的研究方向。
铁死亡是一种近年来发现的与凋亡和坏死及自噬不同的程序性细胞死亡方式，其主要发生机制是在二价铁或脂氧合 酶的作用下，催化细胞中高表达的不饱和脂肪酸发生脂质过氧化，从而诱导细胞死亡。铁死亡参与了多种疾病的发生，如肿瘤、 类风湿性关节炎、神经退行性疾病、缺血再灌注和心脏相关疾病等。肺癌是世界上致死率最高的恶性肿瘤，其治疗策略在不断更 新。近年来，越来越多的研究结果显示，铁死亡与非小细胞肺癌（NSCLC）之间有着紧密的联系。一些在NSCLC的发生发展和治 疗中起重要调节作用的分子（如KRAS、TP53、EGFR等），同样在铁死亡的发生中也发挥作用。此外，在NSCLC中，铁死亡与化学 治疗、放射治疗及免疫治疗也有着密切联系，一些临床前研究证实铁死亡可作为一种“催化剂”，与上述治疗方式联合应用可明显 增强治疗效果，为NSCLC的治疗提供了新的研究方向。
2022, 29(10):950-955.
DOI: 10.3872/j.issn.1007-385X.2022.10.012
Abstract:
近年来肿瘤免疫治疗技术的不断成熟和应用，在多种类型肿瘤的治疗中取得了较好的临床效果，肝细胞癌（HCC）的 免疫治疗也成为最有前景的治疗方式之一。研究发现，磷脂酰肌醇蛋白聚糖 3（GPC3）在HCC组织中特异性高表达，其通过糖基 磷脂酰肌醇（GPI）锚定于细胞膜表面，参与HCC发生发展过程中各种信号通路的调控，可作为特异性肿瘤相关标志物。以GPC3 为靶点的单克隆抗体、双特异性抗体、CAR-T细胞、免疫毒素及相关联合治疗在临床前研究及临床试验中均展现出良好的应用潜 力。因此，靶向GPC3的免疫疗法可能成为未来HCC治疗的主要方向之一，全面了解相关研究的现状对HCC治疗的发展至关重 要。本文综述了以GPC3为靶点的免疫疗法在HCC中的作用机制的研究进展及目前仍存在的问题，并对未来进行展望。
近年来肿瘤免疫治疗技术的不断成熟和应用，在多种类型肿瘤的治疗中取得了较好的临床效果，肝细胞癌（HCC）的 免疫治疗也成为最有前景的治疗方式之一。研究发现，磷脂酰肌醇蛋白聚糖 3（GPC3）在HCC组织中特异性高表达，其通过糖基 磷脂酰肌醇（GPI）锚定于细胞膜表面，参与HCC发生发展过程中各种信号通路的调控，可作为特异性肿瘤相关标志物。以GPC3 为靶点的单克隆抗体、双特异性抗体、CAR-T细胞、免疫毒素及相关联合治疗在临床前研究及临床试验中均展现出良好的应用潜 力。因此，靶向GPC3的免疫疗法可能成为未来HCC治疗的主要方向之一，全面了解相关研究的现状对HCC治疗的发展至关重 要。本文综述了以GPC3为靶点的免疫疗法在HCC中的作用机制的研究进展及目前仍存在的问题，并对未来进行展望。
2022, 29(10):956-961.
DOI: 10.3872/j.issn.1007-385X.2022.10.013
Abstract:
近年来以T细胞为基础的肿瘤免疫治疗发展迅速，但仅对部分肿瘤患者有效，因此亟待探索有效的检测方法和预测 指标。T细胞受体（TCR）是T细胞抗原识别的关键分子。T细胞在胸腺成熟过程中经历了TCR基因重排，形成了TCR高度多样 性，体内所有TCR类型与数量组成TCR组库。借助免疫组库测序技术可得到特定时期肿瘤患者TCR组库的信息，如TCR多样 性、克隆性等特点，为个体化肿瘤免疫治疗方案的选择以及疗效预测提供了新线索。二代测序技术和单细胞测序技术的发展极 大地扩展了TCR组库研究的深度与广度，极大地促进其在肿瘤免疫治疗领域的应用。本文通过对TCR组库测序应用领域、测序 方法及其统计学评估指标进行综述，展示了TCR组库检测作为新型生物标志物来预测及评估患者预后的潜能，为个体精准化肿 瘤免疫治疗提供新策略。
近年来以T细胞为基础的肿瘤免疫治疗发展迅速，但仅对部分肿瘤患者有效，因此亟待探索有效的检测方法和预测 指标。T细胞受体（TCR）是T细胞抗原识别的关键分子。T细胞在胸腺成熟过程中经历了TCR基因重排，形成了TCR高度多样 性，体内所有TCR类型与数量组成TCR组库。借助免疫组库测序技术可得到特定时期肿瘤患者TCR组库的信息，如TCR多样 性、克隆性等特点，为个体化肿瘤免疫治疗方案的选择以及疗效预测提供了新线索。二代测序技术和单细胞测序技术的发展极 大地扩展了TCR组库研究的深度与广度，极大地促进其在肿瘤免疫治疗领域的应用。本文通过对TCR组库测序应用领域、测序 方法及其统计学评估指标进行综述，展示了TCR组库检测作为新型生物标志物来预测及评估患者预后的潜能，为个体精准化肿 瘤免疫治疗提供新策略。
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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.