Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),...Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.展开更多
Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough ...Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience,which focuses on the crosstalk between neural components and tumors.Neuropeptides are a class of highly potent peptides,that perform the physiological functions of neurotransmitters,neuromodulators,and endocrine hormones.Currently,many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication.In addition,neuropeptides and their receptors affect cancer hallmarks such as proliferation,invasion and metastasis,angiogenesis,immune escape,metabolic reprogramming,and others.More importantly,neuropeptides may also affect some tumor comorbidities such as insomnia,depression,anorexia,cancer pain,and others.Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy,not only for treating the tumor itself but also for improving the patient's quality of life.展开更多
基金supported by the National Natural Science Foundation of China(82273202,82370948,82072996,82170941)the Fundamental Research Funds for the Central Universities(2042022dx0003)+1 种基金the Hubei Province International Science and Technology Cooperation Project(2021EHB027)the National Key Research and Development Program(2022YFC2504200).
文摘Cancer immunotherapy using immune-checkpoint inhibitors(ICIs)has revolutionized the field of cancer treatment;however,ICI efficacy is constrained by progressive dysfunction of CD8+tumor-infiltrating lymphocytes(TILs),which is termed T cell exhaustion.This process is driven by diverse extrinsic factors across heterogeneous tumor immune microenvironment(TIME).Simultaneously,tumorigenesis entails robust reshaping of the epigenetic landscape,potentially instigating T cell exhaustion.In this review,we summarize the epigenetic mechanisms governing tumor microenvironmental cues leading to T cell exhaustion,and discuss therapeutic potential of targeting epigenetic regulators for immunotherapies.Finally,we outline conceptual and technical advances in developing potential treatment paradigms involving immunostimulatory agents and epigenetic therapies.
基金supported by the High-Level Talent Introduction Funds from the First Hospital of Lanzhou University(China).
文摘Tumors are complex,highly heterogeneous diseases that place an enormous burden on the world's healthcare systems.Updating understanding of tumor initiation and progression is critical and the current breakthrough lies in cancer neuroscience,which focuses on the crosstalk between neural components and tumors.Neuropeptides are a class of highly potent peptides,that perform the physiological functions of neurotransmitters,neuromodulators,and endocrine hormones.Currently,many studies have shown that many cellular components of the tumor microenvironment express neuropeptides and their receptors and that neuropeptides may play an important role in their cellular communication.In addition,neuropeptides and their receptors affect cancer hallmarks such as proliferation,invasion and metastasis,angiogenesis,immune escape,metabolic reprogramming,and others.More importantly,neuropeptides may also affect some tumor comorbidities such as insomnia,depression,anorexia,cancer pain,and others.Targeting neuropeptides in combination with new therapeutic strategies may significantly advance anti-tumor therapy,not only for treating the tumor itself but also for improving the patient's quality of life.
