Therapeutic tumor vaccines have emerged as promising weapons for inducing robust and durable antitumor immune responses,demonstrating substantial potential for cancer treatment.However,clinical efficacy is significant...Therapeutic tumor vaccines have emerged as promising weapons for inducing robust and durable antitumor immune responses,demonstrating substantial potential for cancer treatment.However,clinical efficacy is significantly hindered by tumor immunogenicity scarcity,antigen presentation deficiency,and immunosuppressive tumor microenvironment.To surmount these obstacles,we proposed an injectable photoimmunological hydrogel vaccine(CRPO/G@ALG)to improve immunotherapy outcomes through the dual mechanism of immunogenic cell death(ICD)induction and dendritic cell(DC)recruitment.The model antigen ovalbumin(OVA)and toll-like receptor 7/8 agonist resiquimod(R848)were incorporated into photothermal copper sulfide nanoparticles(CuS)to construct the nanovaccine CRPO,which was subsequently encapsulated with the granulocyte-macrophage colony-stimulating factor(GM-CSF)in sodium alginate(ALG)to form the hydrogel vaccine CRPO/G@ALG.Following peritumoral administration,CRPO/G@ALG undergoes gelation in response to physiological calcium ions,facilitating the localized retention and controlled release of payloads.Near-infrared(NIR)irradiation triggers ICD in tumor cells,generating an in situ antigen reservoir enriched with tumor-associated antigens(TAAs)to bolster tumor immunogenicity.Concurrently,GM-CSF attracts DCs to infiltrate tumor tissues,while R848 promotes DC maturation and antigen cross-presentation.These synergistic effects prolong the duration of immune stimulation and expand both the breadth and depth of antitumor immunity.In 4T1 tumor-bearing mice,CRPO/G@ALG effectively suppressed primary and distant tumor growth and markedly reduced lung metastasis.Collectively,our findings illustrate the transformative potential of integrating ICD induction,DC recruitment,and hydrogel delivery systems,offering new avenues to advance therapeutic tumor vaccine applications.展开更多
Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fra...Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment resistance.Tumor cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction pathways.However,far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction.Due to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic approach.In this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.展开更多
The tumor microenvironment plays a key role in malignant tumor progression.As a place where tumor cells survive,the tumor microenvironment contains not only tumor cells themselves but also biochemical and biophysical ...The tumor microenvironment plays a key role in malignant tumor progression.As a place where tumor cells survive,the tumor microenvironment contains not only tumor cells themselves but also biochemical and biophysical elements.Tumor cells can change the microenvironment,which in turn affects the survival and development of tumor cells.Tumor malignancy is a highly regulated pathological process following a series of complex cellular-biological events called invasion–metastasis cascades.In this correspondence,we intend to provide a comprehensive background on the tumor environment to inspire further innovations in relevant research areas in the future.展开更多
Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in col...Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration.1,2 For individual cell migration,it has been found that the Rho/ROCK signaling is upregulated and correlates with disease progression.3 Meanwhile,Rho activates myosin-ll and the actomyosin-mediated contraction creates tension within the cells.4,5 However,the roles of the activation of the Rho/RoCK signal pathway in collective cell migration and the precise mechanisms by which myosin-ll fine-tunes the contractility of the cells to allow for the reorganization of the cytoskeleton that drives collective cell migration,remain unclear.This study investigated whether the high cellular contractility could activate the inside-out signal transductions and how did the intracellular force contribute to the collective cell migration.展开更多
基金supported,in whole or in part,by the National Natural Science Foundation of China(52372263,32171395,12132004,32471367)the Sichuan Science and Technology Program(2024NSFSC0601,China)+1 种基金the Program for Innovative Fundamental Research Incubation of UESTC(Y03023206100226,China)the Joint Innovation Fund of Health Commission of Chengdu and Chengdu University of Traditional Chinese Medicine(WXLH202403090,China)ICD(immunogenic cell death)and TEM(tumor microenvironment).
文摘Therapeutic tumor vaccines have emerged as promising weapons for inducing robust and durable antitumor immune responses,demonstrating substantial potential for cancer treatment.However,clinical efficacy is significantly hindered by tumor immunogenicity scarcity,antigen presentation deficiency,and immunosuppressive tumor microenvironment.To surmount these obstacles,we proposed an injectable photoimmunological hydrogel vaccine(CRPO/G@ALG)to improve immunotherapy outcomes through the dual mechanism of immunogenic cell death(ICD)induction and dendritic cell(DC)recruitment.The model antigen ovalbumin(OVA)and toll-like receptor 7/8 agonist resiquimod(R848)were incorporated into photothermal copper sulfide nanoparticles(CuS)to construct the nanovaccine CRPO,which was subsequently encapsulated with the granulocyte-macrophage colony-stimulating factor(GM-CSF)in sodium alginate(ALG)to form the hydrogel vaccine CRPO/G@ALG.Following peritumoral administration,CRPO/G@ALG undergoes gelation in response to physiological calcium ions,facilitating the localized retention and controlled release of payloads.Near-infrared(NIR)irradiation triggers ICD in tumor cells,generating an in situ antigen reservoir enriched with tumor-associated antigens(TAAs)to bolster tumor immunogenicity.Concurrently,GM-CSF attracts DCs to infiltrate tumor tissues,while R848 promotes DC maturation and antigen cross-presentation.These synergistic effects prolong the duration of immune stimulation and expand both the breadth and depth of antitumor immunity.In 4T1 tumor-bearing mice,CRPO/G@ALG effectively suppressed primary and distant tumor growth and markedly reduced lung metastasis.Collectively,our findings illustrate the transformative potential of integrating ICD induction,DC recruitment,and hydrogel delivery systems,offering new avenues to advance therapeutic tumor vaccine applications.
基金National Natural Science Foundation of China,Grant/Award Numbers:U19A2006,12132004,11972111,31900940,32071304,32171309,32171395Sichuan Science and Technology Program,Grant/Award Number:21YJ0130Joint Funds of Center for Engineering Medicine,Grant/Award Numbers:ZYGX2021YGLH017,ZYGX2021YGLH010,ZYGX2021YGLH023。
文摘Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence,progression,invasion,and metastasis of solid tumors.In this process,the tumormicroenvironment(TME)fractures cellular and matrix architecture normality through biochemical and mechanical means,abetting tumorigenesis and treatment resistance.Tumor cells sense and respond to the strength,direction,and duration of mechanical cues in the TME by various mechanotransduction pathways.However,far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction.Due to the great therapeutic difficulties brought by the mechanical changes in the TME,emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves,which has been proven to be a potential therapeutic approach.In this review,we discussed the origins and roles ofmechanical factors in the TME,cell sensing,mechano-biological coupling and signal transduction,in vitro construction of the tumormechanicalmicroenvironment,applications and clinical significance in the TME.
基金supported,in part or in whole,by the National Natural Science Foundation of China(11772088,31700811,11802056,31800780,and 81671821)the Research Program of Sichuan Science and Technology(2017JY0019,2017JY0217,2019YJ0183,and 2019YJ0184)+1 种基金the China Postdoctoral Science Foundation(2017JY0217,2018M640904,and 2019T120831)the Fundamental Research Funds for the Central Universities(ZYGX2016Z001).
文摘The tumor microenvironment plays a key role in malignant tumor progression.As a place where tumor cells survive,the tumor microenvironment contains not only tumor cells themselves but also biochemical and biophysical elements.Tumor cells can change the microenvironment,which in turn affects the survival and development of tumor cells.Tumor malignancy is a highly regulated pathological process following a series of complex cellular-biological events called invasion–metastasis cascades.In this correspondence,we intend to provide a comprehensive background on the tumor environment to inspire further innovations in relevant research areas in the future.
基金supported,in part or in whole,by the National Natural Science Foundation of China(No.32071304,U19A2006,12132004,11972111,and 32171309)the China Postdoctoral Science Foundation(No.2019T120821)+1 种基金the Natural Science Foundation of Sichuan Program(No.23NSFSC3552,2022NSFSC0048,2022NSFSC0686,23SYSX0108,and 2023NSFSC1233)the Joint Funds of Center for Engineering Medicine(No.ZYGX2021YGLH017).
文摘Breast cancerhas been one of the biggest killers of women due to its susceptibility and high metastasis.Pathological observations show that malignant cancer cells frequently invade the surrounding normal tissue in collective rather than individual cell migration.1,2 For individual cell migration,it has been found that the Rho/ROCK signaling is upregulated and correlates with disease progression.3 Meanwhile,Rho activates myosin-ll and the actomyosin-mediated contraction creates tension within the cells.4,5 However,the roles of the activation of the Rho/RoCK signal pathway in collective cell migration and the precise mechanisms by which myosin-ll fine-tunes the contractility of the cells to allow for the reorganization of the cytoskeleton that drives collective cell migration,remain unclear.This study investigated whether the high cellular contractility could activate the inside-out signal transductions and how did the intracellular force contribute to the collective cell migration.
