本研究旨在调查猪胰岛素样生长因子结合蛋白2基因(IGFBP2)潜在的变异与胴体性状和肉质性状之间的关系。IGFBP2是IGFBPs家族的一员,定位在猪15号染色体上。本研究利用PCR-MspⅠ-RFLP方法对该基因第二内含子g.171C>T(Gen Bank Accessio...本研究旨在调查猪胰岛素样生长因子结合蛋白2基因(IGFBP2)潜在的变异与胴体性状和肉质性状之间的关系。IGFBP2是IGFBPs家族的一员,定位在猪15号染色体上。本研究利用PCR-MspⅠ-RFLP方法对该基因第二内含子g.171C>T(Gen Bank Accession No.BV727778)进行了单核苷酸多态性(SNP)检测,在382头大白×梅山猪F2代猪群体中关联分析。结果发现该位点与背膘厚、眼肌高、眼肌宽、骨率等性状呈极显著相关(P<0.01),与眼肌面积、肥肉率、瘦肥比、花油、色值(LD)和色值(BF)等性状呈显著相关(P<0.05)。结果表明IGFBP2基因型与胴体和肉质性能存在一定程度的显著关联,是潜在的影响猪胴体和肉质性状的候选基因。展开更多
目的探讨胰岛素样生长因子结合蛋白2(insulin-like growth factor binding protein 2,IGFBP2)在三阴型乳腺癌(triple-negative breast carcinoma,TNBC)中的表达及其与临床病理特征的关系。方法选取45例TNBC和40例非TNBC病例采用组织芯...目的探讨胰岛素样生长因子结合蛋白2(insulin-like growth factor binding protein 2,IGFBP2)在三阴型乳腺癌(triple-negative breast carcinoma,TNBC)中的表达及其与临床病理特征的关系。方法选取45例TNBC和40例非TNBC病例采用组织芯片方法进行免疫组化SP法染色,观察IGFBP2在两组中的表达情况,并分析其与临床病理特征的关系。结果在TNBC组和非TNBC组中,IGFBP2的阳性率分别是35.6%和85.0%;与非TNBC组相比,TNBC组IGFBP2的表达明显降低(P<0.05),且与患者的淋巴结转移存在相关性(P=0.030),与患者年龄、肿瘤直径、组织学分级、CK5/6或EGFR表达、Ki-67增殖指数、脉管侵犯均无明显相关性。结论与非TNBC相比,TNBC组患者IGFBP2表达下降,且IGFBP2表达与TNBC患者淋巴结转移之间存在明显相关性。展开更多
Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms...Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor burden.Methods:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous tumors.For in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)therapy.Through flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB group.These changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor reduction.Intraperitoneal colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large size.Mechanistically,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor tissues.IGFBP2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive effect by inhibiting the proliferation and activation of CD8^(+)T cells in a PD-L1-dependent fashion.Conclusions:This study suggested that the low efficacy of ICI treatment in HTB tumors is mainly attributed to the intratumoral accumulation of PD-L1^(+)M2-like macrophages via the IGFBP2-STAT3-PD-L1 signaling pathway and their substantial inhibitory effects on T cell proliferation and activation.展开更多
文摘本研究旨在调查猪胰岛素样生长因子结合蛋白2基因(IGFBP2)潜在的变异与胴体性状和肉质性状之间的关系。IGFBP2是IGFBPs家族的一员,定位在猪15号染色体上。本研究利用PCR-MspⅠ-RFLP方法对该基因第二内含子g.171C>T(Gen Bank Accession No.BV727778)进行了单核苷酸多态性(SNP)检测,在382头大白×梅山猪F2代猪群体中关联分析。结果发现该位点与背膘厚、眼肌高、眼肌宽、骨率等性状呈极显著相关(P<0.01),与眼肌面积、肥肉率、瘦肥比、花油、色值(LD)和色值(BF)等性状呈显著相关(P<0.05)。结果表明IGFBP2基因型与胴体和肉质性能存在一定程度的显著关联,是潜在的影响猪胴体和肉质性状的候选基因。
文摘目的探讨胰岛素样生长因子结合蛋白2(insulin-like growth factor binding protein 2,IGFBP2)在三阴型乳腺癌(triple-negative breast carcinoma,TNBC)中的表达及其与临床病理特征的关系。方法选取45例TNBC和40例非TNBC病例采用组织芯片方法进行免疫组化SP法染色,观察IGFBP2在两组中的表达情况,并分析其与临床病理特征的关系。结果在TNBC组和非TNBC组中,IGFBP2的阳性率分别是35.6%和85.0%;与非TNBC组相比,TNBC组IGFBP2的表达明显降低(P<0.05),且与患者的淋巴结转移存在相关性(P=0.030),与患者年龄、肿瘤直径、组织学分级、CK5/6或EGFR表达、Ki-67增殖指数、脉管侵犯均无明显相关性。结论与非TNBC相比,TNBC组患者IGFBP2表达下降,且IGFBP2表达与TNBC患者淋巴结转移之间存在明显相关性。
基金National Natural Science Foundation of China,Grant/Award Numbers:82073303,82103335,82102731Science and Technology Planning Project of Guangzhou,Grant/Award Number:202201011560Natural Science Foundation of Guangdong Province of China,Grant/Award Number:2022A1515012418。
文摘Background:Several clinical studies have uncovered a negative correlation between baseline tumor burden and the efficacy of immune checkpoint inhibitor(ICI)treatment.This study aimed to uncover the specific mechanisms underlying the difference in sensitivity to ICI treatment between tumors with high(HTB)and low(LTB)tumor burden.Methods:For in vivo studies,several mouse models of subcutaneous tumors were established,and transcriptome sequencing,immunohistochemistry,and flow cytometry assays were used to detect the immune status in these subcutaneous tumors.For in vitro experiments,co-culture models,cytokine antibody arrays,western blotting,flow cytometry,and enzyme-linked immunosorbent assays were used to explore the underlying molecular mechanisms Results:We found that MC38 or B16 subcutaneous tumors from the HTB group did not show any response to anti-programmed cell death protein-1(PD-1)therapy.Through flow cytometry assays,we found that the infiltration with CD8^(+)T cellswas significantly decreasedwhereasM2-like macrophageswere enriched in subcutaneous tumors of HTB groups compared with those of LTB group.These changes were not affected by the initial number of injected tumor cells or tumor age,nor could they be reversed by surgical tumor reduction.Intraperitoneal colony-stimulating factor 1 receptor(CSF-1R)inhibitor PLX3397 injection at different time points of tumor growth only had an effect when administered in the early tumor stage to maintain the“heat”of the tumor microenvironment during the process of tumor growth,thereby achieving a response to ICI treatment when the tumor grew to a large size.Mechanistically,we found that insulin-like growth factor binding protein 2(IGFBP2)expression levelswere significantly elevated in HTB tumor tissues.IGFBP2 promoted the programmed death-ligand 1(PD-L1)expression in M2-like macrophages by activating signal transducer and activator of transcription 3(STAT3),and PD-L1^(+)M2-likemacrophages exerted an immunosuppressive effect by inhibiting the proliferation and activation of CD8^(+)T cells in a PD-L1-dependent fashion.Conclusions:This study suggested that the low efficacy of ICI treatment in HTB tumors is mainly attributed to the intratumoral accumulation of PD-L1^(+)M2-like macrophages via the IGFBP2-STAT3-PD-L1 signaling pathway and their substantial inhibitory effects on T cell proliferation and activation.
