Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy ap...Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy approaches,these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells,the extracellular matrix,and blood vessels that form the tumor microenvironment(TME).The TME is known to be heterogeneous and dynamic,exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.TME has been shown in several studies to promote malignancy,angiogenesis,and metastasis in tumors in general and melanoma in particular.Consequently,a significant number of studies in thefield of melanoma therapy have been redirected to investigate the effects of individual TME constituents,their prognostic significance for patients,and the potential of therapeutic intervention to improve overall patient survival.This review highlights novel therapeutic approaches targeting two key resident cell types in the melanoma microenvironment:tumor-associated macrophages(TAMs)and cancer-associatedfibroblasts(CAFs).The review discusses their role in disease progression and summarizes the results of preclinical and clinical trials of targeted therapies against these cell types in the melanoma TME.展开更多
培养人胃癌AGS细胞和人单核细胞THP-1,加入佛波酯诱导为巨噬细胞并用流式细胞术加以鉴定;加入人源IL-4将巨噬细胞极化为M2型巨噬细胞,用流式细胞术检测其表型(CD206)后将M2-TAMS与AGS细胞建立非接触共培养体系,加入不同浓度的氧化苦参碱...培养人胃癌AGS细胞和人单核细胞THP-1,加入佛波酯诱导为巨噬细胞并用流式细胞术加以鉴定;加入人源IL-4将巨噬细胞极化为M2型巨噬细胞,用流式细胞术检测其表型(CD206)后将M2-TAMS与AGS细胞建立非接触共培养体系,加入不同浓度的氧化苦参碱,用qRT-PCR、Wester-Blot技术检测mTOR、Akt信号通路、自噬标记性基因Beclin-1的表达情况,检测并分析氧化苦参碱对共培养后人胃癌细胞增殖和侵袭的影响。结果表明THP-1加入佛波酯诱导为巨噬细胞的最佳时间及浓度为24 h 50 ng/ml,极化为M2-TAMs最佳条件为加入IL-424 h 20 ng/ml。在氧化苦参碱的作用下诱导了TAMs自噬,mTOR信号通路受到抑制,同时抑制了胃癌细胞的增殖和侵袭能力。展开更多
Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising canc...Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.展开更多
基金performed at the expense of the subsidy allocated to Kazan Federal University for the fulfillment of the stated task in the field of scientific activity,No.FZSM-2023-0011.
文摘Melanoma is a malignant neoplasm with a high propensity to metastasize,arising from melanocytes and contributing significantly to global morbidity and mortality.Despite the demonstrated efficacy of many immunotherapy approaches,these methods rely on direct destruction of tumor cells with minimal impact on the aggregate of nearby non-tumor cells,the extracellular matrix,and blood vessels that form the tumor microenvironment(TME).The TME is known to be heterogeneous and dynamic,exerting both antitumor and pro-tumor effects depending on the specific features and stage of carcinogenesis.TME has been shown in several studies to promote malignancy,angiogenesis,and metastasis in tumors in general and melanoma in particular.Consequently,a significant number of studies in thefield of melanoma therapy have been redirected to investigate the effects of individual TME constituents,their prognostic significance for patients,and the potential of therapeutic intervention to improve overall patient survival.This review highlights novel therapeutic approaches targeting two key resident cell types in the melanoma microenvironment:tumor-associated macrophages(TAMs)and cancer-associatedfibroblasts(CAFs).The review discusses their role in disease progression and summarizes the results of preclinical and clinical trials of targeted therapies against these cell types in the melanoma TME.
文摘培养人胃癌AGS细胞和人单核细胞THP-1,加入佛波酯诱导为巨噬细胞并用流式细胞术加以鉴定;加入人源IL-4将巨噬细胞极化为M2型巨噬细胞,用流式细胞术检测其表型(CD206)后将M2-TAMS与AGS细胞建立非接触共培养体系,加入不同浓度的氧化苦参碱,用qRT-PCR、Wester-Blot技术检测mTOR、Akt信号通路、自噬标记性基因Beclin-1的表达情况,检测并分析氧化苦参碱对共培养后人胃癌细胞增殖和侵袭的影响。结果表明THP-1加入佛波酯诱导为巨噬细胞的最佳时间及浓度为24 h 50 ng/ml,极化为M2-TAMs最佳条件为加入IL-424 h 20 ng/ml。在氧化苦参碱的作用下诱导了TAMs自噬,mTOR信号通路受到抑制,同时抑制了胃癌细胞的增殖和侵袭能力。
基金supported by the Liaoning Provincial Department of Education youth project(No.LJKQZ20222355,China).
文摘Reactive oxygen species(ROS)generated from photosensitizers exhibit great potential for repolarizing immunosuppressive tumor-associated macrophages(TAMs)toward the anti-tumor M1 phenotype,representing a promising cancer immunotherapy strategy.Nevertheless,their effectiveness in eliminating solid tumors is generally limited by the instability and inadequate TAMs-specific targeting of photosensitizers.Here,a novel core-shell integrated nano platform is proposed to achieve a coordinated strategy of repolarizing TAMs for potentiating cancer immunotherapy.Colloidal mesoporous silica nanoparticles(CMSN)are fabricated to encapsulate photosensitizer-Indocyanine Green(ICG)to improve their stability.Then ginseng-derived exosome(GsE)was coated on the surface of ICG/CMSN for targeting TAMs,as well as repolarizing TAMs concurrently,named ICG/CMSN@GsE.As expected,with the synergism of ICG and GsE,ICG/CMSN@GsE exhibited better stability,mild generation of ROS,favorable specificity toward M2-like macrophages,enhancing drug retention in tumors and superior TAMs repolarization potency,then exerted a potent antitumor effect.In vivo,experiment results also confirm the synergistic suppression of tumor growth accompanied by the increased presence of anti-tumor M1-like macrophages and maximal tumor damage.Taken together,by integrating the superiorities of TAMs targeting specificity and synergistic TAMs repolarization effect into a single nanoplatform,ICG/CMSN@GsE can readily serve as a safe and high-performance nanoplatform for enhanced cancer immunotherapy.
