In recent years,immune checkpoint inhibitors(ICIs)have made significant breakthroughs in the treatment of various tumors,greatly improving clinical efficacy.As the fifth most common antitumor treatment strategy for pa...In recent years,immune checkpoint inhibitors(ICIs)have made significant breakthroughs in the treatment of various tumors,greatly improving clinical efficacy.As the fifth most common antitumor treatment strategy for patients with solid tumors after surgery,chemotherapy,radiotherapy and targeted therapy,the therapeutic response to ICIs largely depends on the number and spatial distribution of effector T cells that can effectively identify and kill tumor cells,features that are also important when distinguishing malignant tumors from“cold tumors”or“hot tumors”.At present,only a small proportion of colorectal cancer(CRC)patients with deficient mismatch repair(dMMR)or who are microsatellite instability-high(MSI-H)can benefit from ICI treatments because these patients have the characteristics of a“hot tumor”,with a high tumor mutational burden(TMB)and massive immune cell infiltration,making the tumor more easily recognized by the immune system.In contrast,a majority of CRC patients with proficient MMR(pMMR)or who are microsatellite stable(MSS)have a low TMB,lack immune cell infiltration,and have almost no response to immune monotherapy;thus,these tumors are“cold”.The greatest challenge today is how to improve the immunotherapy response of“cold tumor”patients.With the development of clinical research,immunotherapies combined with other treatment strategies(such as targeted therapy,chemotherapy,and radiotherapy)have now become potentially effective clinical strategies and research hotspots.Therefore,the question of how to promote the transformation of“cold tumors”to“hot tumors”and break through the bottleneck of immunotherapy for cold tumors in CRC patients urgently requires consideration.Only by developing an in-depth understanding of the immunotherapy mechanisms of cold CRCs can we screen out the immunotherapy-dominant groups and explore the most suitable treatment options for individuals to improve therapeutic efficacy.展开更多
Cold therapy has been used regularly as an immediate treatment to induce analgesia following acute soft-tissue injuries,however,a prolonged ice application has proved to delay the start of the healing and lengthen the...Cold therapy has been used regularly as an immediate treatment to induce analgesia following acute soft-tissue injuries,however,a prolonged ice application has proved to delay the start of the healing and lengthen the recovery process.Hyperbaric gaseous cryotherapy,also known as neurocryostimulation,has shown the ability to overcome most of the limitations of traditional cold therapy,and meanwhile promotes the analgesic and anti-inflammatory effects well,but the current existing studies have shown conflicting results on its effects.Traditional cold therapy still has beneficial effect especially when injuries are severe and swelling is the limiting factor for recovery after soft-tissue injuries,and therefore no need to be entirely put out to pasture in the rehabilitation practice.Strong randomized controlled trials with good methodological quality are still needed in the future to evaluate the effects of different cryotherapy modalities.展开更多
Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration...Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.展开更多
基金Supported by National Natural Science Foundation of China,No.82073338Sichuan Science and Technology Support Project,No.2021YFSY0039 and No.22ZDYF0499+1 种基金The 1·3·5 Project for Disciplines of Excellence-Clinical Research Incubation Project West China Hospital,Sichuan University,No.2020HXFH002The 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University,No.ZYJC21059.
文摘In recent years,immune checkpoint inhibitors(ICIs)have made significant breakthroughs in the treatment of various tumors,greatly improving clinical efficacy.As the fifth most common antitumor treatment strategy for patients with solid tumors after surgery,chemotherapy,radiotherapy and targeted therapy,the therapeutic response to ICIs largely depends on the number and spatial distribution of effector T cells that can effectively identify and kill tumor cells,features that are also important when distinguishing malignant tumors from“cold tumors”or“hot tumors”.At present,only a small proportion of colorectal cancer(CRC)patients with deficient mismatch repair(dMMR)or who are microsatellite instability-high(MSI-H)can benefit from ICI treatments because these patients have the characteristics of a“hot tumor”,with a high tumor mutational burden(TMB)and massive immune cell infiltration,making the tumor more easily recognized by the immune system.In contrast,a majority of CRC patients with proficient MMR(pMMR)or who are microsatellite stable(MSS)have a low TMB,lack immune cell infiltration,and have almost no response to immune monotherapy;thus,these tumors are“cold”.The greatest challenge today is how to improve the immunotherapy response of“cold tumor”patients.With the development of clinical research,immunotherapies combined with other treatment strategies(such as targeted therapy,chemotherapy,and radiotherapy)have now become potentially effective clinical strategies and research hotspots.Therefore,the question of how to promote the transformation of“cold tumors”to“hot tumors”and break through the bottleneck of immunotherapy for cold tumors in CRC patients urgently requires consideration.Only by developing an in-depth understanding of the immunotherapy mechanisms of cold CRCs can we screen out the immunotherapy-dominant groups and explore the most suitable treatment options for individuals to improve therapeutic efficacy.
文摘Cold therapy has been used regularly as an immediate treatment to induce analgesia following acute soft-tissue injuries,however,a prolonged ice application has proved to delay the start of the healing and lengthen the recovery process.Hyperbaric gaseous cryotherapy,also known as neurocryostimulation,has shown the ability to overcome most of the limitations of traditional cold therapy,and meanwhile promotes the analgesic and anti-inflammatory effects well,but the current existing studies have shown conflicting results on its effects.Traditional cold therapy still has beneficial effect especially when injuries are severe and swelling is the limiting factor for recovery after soft-tissue injuries,and therefore no need to be entirely put out to pasture in the rehabilitation practice.Strong randomized controlled trials with good methodological quality are still needed in the future to evaluate the effects of different cryotherapy modalities.
基金the grants from National Natural Science Foundation of China(21602030 and 81872808)Program of Shanghai Academic Research Leader(18XD1400500)+2 种基金Project Supported by Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Fudan-SIMM Joint Research Fund(FU-SIMM20182006)Scientific Research Program of Shanghai Health and Family Planning Commission(20184Y0149).
文摘Although current anticancer immunotherapies using immune checkpoint inhibitors(ICIs)have been reported with a high clinical success rate,numerous patients still bear‘cold’tumors with insufficient T cell infiltration and low immunogenicity,responding poorly to ICI therapy.Considering the advancements in precision medicine,in-depth mechanism studies on the tumor immune microenvironment(TIME)among cold tumors are required to improve the treatment for these patients.Nanomedicine has emerged as a promising drug delivery system in anticancer immunotherapy,activates immune function,modulates the TIME,and has been applied in combination with other anticancer therapeutic strategies.This review initially summarizes the mechanisms underlying immunosuppressive TIME in cold tumors and addresses the recent advancements in nanotechnology for cold TIME reversal-based therapies,as well as a brief talk about the feasibility of clinical translation.
