Reviews The Dectin-1 cluster comprises seven members:CLEC-12A,CLEC-12B,CLEC-1A,CLEC-7A,CLEC-2,CLEC-9A and OLR1.These members have been demonstrated to be involved in the tumorigenesis,progression,and metastasis of sev...Reviews The Dectin-1 cluster comprises seven members:CLEC-12A,CLEC-12B,CLEC-1A,CLEC-7A,CLEC-2,CLEC-9A and OLR1.These members have been demonstrated to be involved in the tumorigenesis,progression,and metastasis of several cancers.However,little is known about their roles in human lung adenocarcinoma(LUAD).The expression patterns of the Dectin-1 cluster were analyzed via the ONCOMINE and GEPIA databases.We evaluated the prognostic value of the Dectin-1 cluster in patients with LUAD using the Kaplan-Meier plotter and GEPIA.Differential expression was validated with the EMBL-EBI database,and protein expression was analyzed with the HPA database.In addition,protein-protein interaction network,GO,and KEGG analyses were conducted.Finally,the correlations between CLEC-12A and immune molecules(immune inhibitors and MHC molecules)were investigated via TISIDB and GEPIA.The expression levels of Dectin-1 cluster genes were downregulated in LUAD tissues compared to those in normal lung tissues.The expression levels of CLEC-12A,CLEC-12B,CLEC-2,and CLEC-9A correlated with tumor stage,and CLEC-12A and CLEC-12B were significantly associated with survival in patients with LUAD.The seven genes mostly participated in immune regulation processes and were involved in autoimmune disorders and hematological malignancies.Finally,correlation analyses revealed CLEC-12A expression was associated with most immune inhibitors and MHCs.CLEC-12A was positively related to PD-1,PD-L1,PD-L2,CTLA4,TIM3,and LAG3.In conclusion,our findings suggest that CLEC-12A and CLEC-12B can be used as prognostic biomarkers in LUAD.CLEC-12A expression was associated with immune checkpoint molecules,and CLEC-12A may be a potential assistant target to improve the efficacy of immune checkpoint inhibitors immunotherapy.展开更多
Small cell lung cancer(SCLC),a highly lethal lung cancer sub-type with distinct neuroendocrine-like features,accounts for 10%–15%of all lung cancers.The overall 5-year survival rate remains less than 10%.SCLC is char...Small cell lung cancer(SCLC),a highly lethal lung cancer sub-type with distinct neuroendocrine-like features,accounts for 10%–15%of all lung cancers.The overall 5-year survival rate remains less than 10%.SCLC is characterized by early metastasis,thus minimizing the potential patient benefits of surgery.In recent decades,the first-line treatment for SCLC has remained chemotherapy combining etoposide and cisplatin(E/P).Despite high rates of response to E/P treatment,SCLC eventually relapses and is almost universally resistant to treatment at recurrence,thus making SCLC a recalcitrant malignancy.Moreover,the limited knowledge regarding the molecular mechanisms underlying SCLC metastasis and resistance greatly hinders improvements in overall SCLC survival.To better understand the molecular mechanisms of SCLC and discover potential therapeutic targets,extensive efforts have continued for decades.展开更多
Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human c...Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials.However,the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored.Here,we demonstrate that oxidized mitochondrial DNA(mtDNA)and stimulator of interferon genes(STING)signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine.Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells.Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells(DCs).Oxidized mtDNA,as a DAMP or adjuvant,activated the STING-TBK1-IRF3-IFN-β pathway in DCs,which subsequently cross-presented irradiated tumor cell-derived antigens to CD8^(+)T cells and elicited antitumor immunity.The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity,which may have implications for new strategies to improve the efficacy of irradiated vaccines.展开更多
Microbiome research has extended into the cancer area in the past decades.Microbes can affect oncogenesis,progression,and treatment response through various mechanisms,including direct regulation and indirect impacts....Microbiome research has extended into the cancer area in the past decades.Microbes can affect oncogenesis,progression,and treatment response through various mechanisms,including direct regulation and indirect impacts.Microbiota-associated detectionmethods and agents have been developed to facilitate cancer diagnosis and therapy.Additionally,the cancermicrobiome has recently been redefined.The identification of intra-tumoral microbes and cancer-related circulating microbial DNA(cmDNA)has promoted novel research in the cancer–microbiome area.In this review,we define the human system of commensal microbes and the cancer microbiome from a brand-new perspective and emphasize the potential value of cmDNA as a promising biomarker in cancer liquid biopsy.We outline all existing studies on the relationship between cmDNA and cancer and the outlook for potential preclinical and clinical applications of cmDNA in cancer precision medicine,as well as critical problems to be overcome in this burgeoning field.展开更多
To the Editor:Immune checkpoint inhibitors(ICIs)have shown remarkable clinical responses;however,their efficacy remains limited to a small subset of patients.Peripheral blood mononuclear cells(PBMCs)offer an effective...To the Editor:Immune checkpoint inhibitors(ICIs)have shown remarkable clinical responses;however,their efficacy remains limited to a small subset of patients.Peripheral blood mononuclear cells(PBMCs)offer an effective,accessible,and minimally invasive approach to assess tumor immune status and identify ICI responders.In this study,we aimed to elucidate the role of PBMC gene expression in ICI treatment response and prognosis.This study received approval from the Biomedical Ethics Committee of West China Hospital,Sichuan University(No.2019[1045])and the requirement to obtain informed consent was waived.展开更多
The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar...The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells,which we term as confused cell identity(CCI).CCI is an independent prognostic marker associated with poor prognosis in ESCC.Further,we identify tropomyosin 4(TPM4)as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo.And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway.Thus,our study suggests an unrecognized feature of ESCC cells,which might be of value for clinic prognosis and potential interference.展开更多
基金supported by the China Postdoctoral Science Foundation[Grant No.2018M643495]Technology Department of Sichuan Province[Grant No.2020YJ0049].
文摘Reviews The Dectin-1 cluster comprises seven members:CLEC-12A,CLEC-12B,CLEC-1A,CLEC-7A,CLEC-2,CLEC-9A and OLR1.These members have been demonstrated to be involved in the tumorigenesis,progression,and metastasis of several cancers.However,little is known about their roles in human lung adenocarcinoma(LUAD).The expression patterns of the Dectin-1 cluster were analyzed via the ONCOMINE and GEPIA databases.We evaluated the prognostic value of the Dectin-1 cluster in patients with LUAD using the Kaplan-Meier plotter and GEPIA.Differential expression was validated with the EMBL-EBI database,and protein expression was analyzed with the HPA database.In addition,protein-protein interaction network,GO,and KEGG analyses were conducted.Finally,the correlations between CLEC-12A and immune molecules(immune inhibitors and MHC molecules)were investigated via TISIDB and GEPIA.The expression levels of Dectin-1 cluster genes were downregulated in LUAD tissues compared to those in normal lung tissues.The expression levels of CLEC-12A,CLEC-12B,CLEC-2,and CLEC-9A correlated with tumor stage,and CLEC-12A and CLEC-12B were significantly associated with survival in patients with LUAD.The seven genes mostly participated in immune regulation processes and were involved in autoimmune disorders and hematological malignancies.Finally,correlation analyses revealed CLEC-12A expression was associated with most immune inhibitors and MHCs.CLEC-12A was positively related to PD-1,PD-L1,PD-L2,CTLA4,TIM3,and LAG3.In conclusion,our findings suggest that CLEC-12A and CLEC-12B can be used as prognostic biomarkers in LUAD.CLEC-12A expression was associated with immune checkpoint molecules,and CLEC-12A may be a potential assistant target to improve the efficacy of immune checkpoint inhibitors immunotherapy.
基金supported by grant from the National Natural Science Foundation of China(Grant No.82102779).
文摘Small cell lung cancer(SCLC),a highly lethal lung cancer sub-type with distinct neuroendocrine-like features,accounts for 10%–15%of all lung cancers.The overall 5-year survival rate remains less than 10%.SCLC is characterized by early metastasis,thus minimizing the potential patient benefits of surgery.In recent decades,the first-line treatment for SCLC has remained chemotherapy combining etoposide and cisplatin(E/P).Despite high rates of response to E/P treatment,SCLC eventually relapses and is almost universally resistant to treatment at recurrence,thus making SCLC a recalcitrant malignancy.Moreover,the limited knowledge regarding the molecular mechanisms underlying SCLC metastasis and resistance greatly hinders improvements in overall SCLC survival.To better understand the molecular mechanisms of SCLC and discover potential therapeutic targets,extensive efforts have continued for decades.
基金This work was supported by the National Natural Science Foundation Regional Innovation and Development(No.U19A2003)National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2018ZX09733001)+1 种基金Excellent Youth Foundation of the Sichuan Scientific Committee Grant in China(No.2019JDJQ008)Development Program of China(No.2016YFA0201402).
文摘Exposure to ionizing radiation,a physical treatment that inactivates live tumor cells,has been extensively applied to enhance the antitumor responses induced by cancer cell vaccines in both animal research and human clinical trials.However,the mechanisms by which irradiated cells function as immunogenic tumor vaccines and induce effective antitumor responses have not been fully explored.Here,we demonstrate that oxidized mitochondrial DNA(mtDNA)and stimulator of interferon genes(STING)signaling play a key roles in the enhanced antitumor effect achieved with an irradiated tumor cell vaccine.Elevations in ROS and oxidized mtDNA 8-OHG content could be induced in irradiated tumor cells.Oxidized mtDNA derived from irradiated tumor cells gained access to the cytosol of dendritic cells(DCs).Oxidized mtDNA,as a DAMP or adjuvant,activated the STING-TBK1-IRF3-IFN-β pathway in DCs,which subsequently cross-presented irradiated tumor cell-derived antigens to CD8^(+)T cells and elicited antitumor immunity.The results of our study provide insight into the mechanism by which an irradiated cell vaccine mediates antitumor immunity,which may have implications for new strategies to improve the efficacy of irradiated vaccines.
基金Thisworkwas supported by the National Natural Science Foundation Regional Innovation and Development(grant No.U20A20394)the Project of Science and Technology Department of Sichuan Province(grant No.2020YJ0106).
文摘Microbiome research has extended into the cancer area in the past decades.Microbes can affect oncogenesis,progression,and treatment response through various mechanisms,including direct regulation and indirect impacts.Microbiota-associated detectionmethods and agents have been developed to facilitate cancer diagnosis and therapy.Additionally,the cancermicrobiome has recently been redefined.The identification of intra-tumoral microbes and cancer-related circulating microbial DNA(cmDNA)has promoted novel research in the cancer–microbiome area.In this review,we define the human system of commensal microbes and the cancer microbiome from a brand-new perspective and emphasize the potential value of cmDNA as a promising biomarker in cancer liquid biopsy.We outline all existing studies on the relationship between cmDNA and cancer and the outlook for potential preclinical and clinical applications of cmDNA in cancer precision medicine,as well as critical problems to be overcome in this burgeoning field.
基金National Natural Science Foundation of China(No.NSFC82372331)Project of Science and Technology Department of Sichuan Province(Nos.2024NSFSC1551 and 2023NSFSC0716)
文摘To the Editor:Immune checkpoint inhibitors(ICIs)have shown remarkable clinical responses;however,their efficacy remains limited to a small subset of patients.Peripheral blood mononuclear cells(PBMCs)offer an effective,accessible,and minimally invasive approach to assess tumor immune status and identify ICI responders.In this study,we aimed to elucidate the role of PBMC gene expression in ICI treatment response and prognosis.This study received approval from the Biomedical Ethics Committee of West China Hospital,Sichuan University(No.2019[1045])and the requirement to obtain informed consent was waived.
基金We thank the members of the CC-LY laboratory for their technical support and suggestions,and the Core Facilities of West China Hospital.This work was supported by the National Key R&D Program of China(2017YFA0505600)the National Natural Science Foundation of China(81522003,82170171,81770157,and 82003156)+1 种基金the Sichuan Science and Technology Program(2020YFQ0059,2018JZ0077,2017TJPT0005,2022YFS0171 and 2022YFS0205)1.3.5.Project for Disciplines of Excellence,West China Hospital,Sichuan University,and the innovation initiative of Sichuan University,Grant no.2018SCUH0060.We thank the Chengdu OrganoidMed Medical Laboratory for their technical support.We also thank BioRender(biorender.com)for providing items for drawing scheme graphs.
文摘The cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer.Here,we report that esophageal squamous cell carcinoma(ESCC)cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells,which we term as confused cell identity(CCI).CCI is an independent prognostic marker associated with poor prognosis in ESCC.Further,we identify tropomyosin 4(TPM4)as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo.And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway.Thus,our study suggests an unrecognized feature of ESCC cells,which might be of value for clinic prognosis and potential interference.
