The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies oft...The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.展开更多
Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity ...Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint signaling.Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress.Furthermore,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.展开更多
Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)...Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T cells.Using bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB level.We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell infiltration.Using pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI efficacy.Among the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo studies.Additionally,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.展开更多
Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immun...Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy.However,instead of a straightforward combination of multiple therapeutics,it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies,which are based on a comprehensive understanding of the physiological and pathological features.In this case,the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes.Therefore,the concept of Sequential Drug Delivery System(SDDS)is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions,thus complying with the dynamic disease evolution and the human immunity.This review summarizes the recent advancements inbiomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy.Furthermore,the rationales behind various engineering strategies are discussed.Finally,an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.展开更多
Therapeutic cancer vaccines have experienced a resurgence over the past ten years.Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle,primarily by activating the immune syste...Therapeutic cancer vaccines have experienced a resurgence over the past ten years.Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle,primarily by activating the immune system to promote tumor regression and overcome immune resistance.In this review,we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle,including the effector cell function,infiltration,initiation,and exhaustion.We summarize the identification of tumor antigens and their delivery through cancer vaccines.We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy.Additionally,the impact of aging and myelosuppression,two prevalent forms of immunological stress,on the effectiveness of therapeutic cancer vaccines is deliberated.Finally,we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.展开更多
基金supported by the National Natural Science Foundation of China(22007106,31800842,31922042 and 81771966)Technology&Innovation Commission of Shenzhen Municipality(JCYJ20180507181654186 and JCYJ20170818162637217,China)+1 种基金the Fundamental Research Funds for the Central Universities(2020-RC320-002 and 2019PT320028)the China Postdoctoral Science Foundation(2019TQ0396,China)。
文摘The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death(ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators.Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
基金the National Natural Science Foundation of China(Nos.82322073,82173846,and 82304533)CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2023-I2M-3-009,China)+11 种基金Oriental Scholars of Shanghai Universities(TP2022081,China)China Postdoctoral Science Foundation(No.2021M702215)Jiangxi Province Thousand Talents Program(jxsq2023102168,China)Young Talent Lifting Project of Young Talent Lifting Project of China Association of Chinese Medicine[No.CACM-(2021-QNRC2-A08)]Shanghai Rising-Star Program(No.22QA1409100,China)Shanghai Sailing Program(No.22YF1445000,China)2021 Shanghai Science and Technology Innovation Action Plan(No.21S11902800,China)Three-Year Action Plan for Three-year Action Plan for Shanghai TCM Development and Inheritance Program[No.ZY(2021-2023)-0208 and ZY(2021-2023)-0401,China]High level Key Discipline of National Administration of Traditional Chinese Medicine(No.zyyzdxk-2023071,China)Innovation Team and Talents Cultivation Program of High level Key Discipline of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202004,China)Key project at central government level:The ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302,China)Innovation team of high-level local universities in Shanghai:Strategic Innovation Team of TCM Chemical Biology(China).All figures were created with BioRender.com.
文摘Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer therapy.As vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target efficacy.This review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint signaling.Particular attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical progress.Furthermore,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.
基金supported by the National Natural Science Foundation of China(81930065,82173128,82102921,and 82003269)the Cancer Innovation Research Program of Sun Yat-sen University Cancer Center(CIRP-SYSUCC-0004)+5 种基金the Swedish Research Council(VR-MH 2014-46602-117891-30)the CAMS Innovation Fund for Medical Sciences(CIFMS)(2019-I2M-5-036)the Youth Teacher Cultivation Program of Sun Yat-sen UniversityGuangdong Provincial Clinical Medical Research Center for Malignant Tumors(84000-31660002)the China Postdoctoral Science Foundation(2023M744049)the Chih Kuang Scholarship for Outstanding Young Physician-Scientists of Sun Yat-sen University Cancer Center(CKS-SYSUCC-2023001)。
文摘Patients with high tumor mutational burden(TMB)levels do not consistently respond to immune checkpoint inhibitors(ICIs),possibly because a high TMB level does not necessarily result in adequate infiltration of CD8^(+)T cells.Using bulk ribonucleic acid sequencing(RNA-seq)data from 9311 tumor samples across 30 cancer types,we developed a novel tool called the modulator of TMB-associated immune infiltration(MOTIF),which comprises genes that can determine the extent of CD8^(+)T cell infiltration prompted by a certain TMB level.We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle.By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors,we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8^(+)T cell infiltration.Using pretreatment RNA-seq data from 13 ICI-treated cohorts,we validated the use of MOTIF in predicting CD8^(+)T cell infiltration and ICI efficacy.Among the components of MOTIF,we identified EMC3 as a negative regulator of CD8^(+)T cell infiltration,which was validated via in vivo studies.Additionally,MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8^(+)T cell infiltration and improve ICI efficacy.
基金supported by the National Natural Science Foundation of China(22478438,81972894,82303820,82273882,32401048 and 22278442)the Science Fund for Distinguished Young Scholars of Jiangsu Province(BK20240098,China)+4 种基金the Natural Science Foundation of Jiangsu Province(BK20231017,China)the China Postdoctoral Science Foundation(2023M733891)the Jiangsu Funding Program for Excellent Postdoctoral Talent(317717,China)the Fundamental Research Funds for the Central Universities(2632023GR11,China)the Special Research Fund from the State Key Laboratory of Natural Medicines at China Pharmaceutical University(SKLNMZZ2024JS19).
文摘Over the past few decades,tumor immunotherapy has revolutionized the landscape of cancer clinical treatment.There is a flourishing development of combination strategies to improve the anti-tumor efficacy of mono-immunotherapy.However,instead of a straightforward combination of multiple therapeutics,it is more preferable to pursue a synergistic effect by designing rational combinations as well as administration strategies,which are based on a comprehensive understanding of the physiological and pathological features.In this case,the timing and spatial distribution of the combination drugs become essential factors in achieving improved therapeutic outcomes.Therefore,the concept of Sequential Drug Delivery System(SDDS)is proposed to define the spatiotemporally programmed drug delivery/release through triggers of internal conditions and/or external interventions,thus complying with the dynamic disease evolution and the human immunity.This review summarizes the recent advancements inbiomaterial-based SDDSs used for spatiotemporally-tuned combination tumor immunotherapy.Furthermore,the rationales behind various engineering strategies are discussed.Finally,an overview of potential synergistic mechanisms as well as their prospects for combination immunotherapy is presented.
基金supported by grants from the National Key R&D Program of China(No.2022YFC2304104 to Wenjun Wang and No.2019YFA0905903 to Mingzhao Zhu)the Beijing Municipal Science&Technology Commission(No.L232008 to Mingzhao Zhu).
文摘Therapeutic cancer vaccines have experienced a resurgence over the past ten years.Cancer vaccines are typically designed to enhance specific stages of the cancer-immunity cycle,primarily by activating the immune system to promote tumor regression and overcome immune resistance.In this review,we summarize the significant recent advancements in cancer immunotherapy based on the cancer-immunity cycle,including the effector cell function,infiltration,initiation,and exhaustion.We summarize the identification of tumor antigens and their delivery through cancer vaccines.We discuss how specific stages of the cancer-immunity cycle have been leveraged to augment anti-tumor immune responses and improve vaccine efficacy.Additionally,the impact of aging and myelosuppression,two prevalent forms of immunological stress,on the effectiveness of therapeutic cancer vaccines is deliberated.Finally,we summarize the current status of various therapeutic cancer vaccines at different clinical trial phases.
