简介:Tumorgrowthandmetastasisareangiogenesis-dependent.Anti-angiogenictherapymaybeausefulapproachtocancertherapy.Thisreviewdiscussedtumorangiogenesisandimmunotherapyoftargetingtumorangiogenesisfromtwomainaspects:(1)activevaccinationtoinduceeffectiveanti-angiogenesisimmunity;(2)passiveimmunotherapywithanti-pro-angiogenicmoleculesrelevantantibody.Evidencefromtherecentyearssuggestedthatanti-angiogenictherapyshouldbeoneofthemostpromisingapproachestocancertherapy.
简介:Beingoneofthemostabundantintracellularproteins,heatshockproteins(HSPs)havemanyhousekeepingfunctionswhicharecrucialforthesurvivaloforganisms.Inaddition,someHSPsarenewimmunoactivemoleculeswhichplayimportantrolesinbothadaptiveandinnateimmunity.TheycouldactivateCD8^+andCD4^+lymphocytes,induceinnateimmuneresponseincludingnaturalkiller(NK)cellactivationandcytokinesecretion,andinducematurationofdendriticcells(DCs).Thesecharacteristicshavebeenusedforimmunotherapyofvarioustypesofcancersandinfectiousdisenses.ThisreviewfocusesonthemainHSPfamilies——HSP70and90families.ThemechanismofHSPs’functioninelicitingimmuneresponseareelucidatedandvariousformsofHSPsusedinimmunotherapyarediscussedindetails.Attheendofthisreview,authorssummarizeclinicaltrialsrelatedtoHSPsandevaluatetheirclinicalefficacy.
简介:AbstractMedulloblastoma is the most common primary pediatric malignancy of the central nervous system. Recurrent and refractory patients account for approximately 30% of them. Immune cells are an important component of the brain tumor microenvironment, including tumor-associated macrophages, T lymphocytes, natural killer cells, dendritic cells, neutrophils and B lymphocytes. Understanding how they behave and interact is important in the investigation of the onset and progression of medulloblastoma. Here, we overview the features and recent advances of each component of immune cells in medulloblastoma. Meanwhile, immunotherapy is a promising but also challenging treatment strategy for medulloblastoma. At present, there are a growing number of immunotherapeutic approaches under investigation including immune checkpoint inhibitors, oncolytic viruses, cancer vaccines, chimeric antigen receptor T cell therapies, and natural killer cells in recurrent and refractory medulloblastoma patients.
简介:一个适当小动物模型的缺乏仍然是一个主要障碍因为学习immunotolerance和immunopathogenesis由肝炎B病毒(HBV)导致了感染。在这研究,我们与recombinant在感染以后与持续HBVviremia报导一个老鼠模型带一个可复制的HBV染色体(AAV/HBV)的联系adeno的病毒(AAV)。类似于临床的HBV搬运人,感染AAV/HBV的老鼠为对HBV表面抗原(HBsAg)的抗体是sero否定的。有面对铝助手疫苗的常规HBV的免疫没能在这些老鼠对HBV得到有免疫力的回答。为了识别一支疫苗,那能潜在地围绕这忍耐,TLR9收缩筋CpG作为一个助手被加到HBsAg。有HBsAg/CpG的老鼠的种痘导致了viremia,而且强壮的抗体生产和T房间回答的不仅清理。而且,DNA复制和HBV的蛋白质表示显著地在AAV/HBV-infected鼠标的肝被减少。因此,AAV/HBV-infected老鼠可以作为一个柔韧的模型被使用调查HBVimmunotolerance并且为开发新奇免疫疗法根除的内在的机制HBV感染。
简介:Differentapproachesfortreatinglungcancerhavebeendevelopedovertime,includingchemotherapy,radiotherapyandtargetedtherapiesagainstactivatingmutations.Lately,betterunderstandingoftheroleoftheimmunologicalsystemintumorcontrolhasopenedmultipledoorstoimplementdifferentstrategiestoenhanceimmuneresponseagainstcancercells.Itisknownthattumorcellseludeimmuneresponsebyseveralmechanisms.Thedevelopmentofmonoclonalantibodiesagainstthecheckpointinhibitorprogrammedcelldeathprotein1(PD-1)anditsligand(PD-L1),onTcells,hasledtohighactivityincancerpatientswithlonglastingresponses.Nivolumab,anantiPD-1inhibitor,hasbeenrecentlyapprovedforthetreatmentofsquamouscelllungcancerpatients,giventhesurvivaladvantagedemonstratedinaphaseIIItrial.Pembrolizumab,anotherantiPD-1antibody,hasreceivedFDAbreakthroughtherapydesignationfortreatmentofnon-smallcelllungcancer(NSCLC),supportedbydatafromaphaseItrial.ClinicaltrialswithantiPD-1/PD-L1antibodiesinNSCLChavedemonstratedverygoodtolerabilityandactivity,withresponseratesaround20%andamediandurationofresponseof18months.
简介:AbstractImmunotherapy has become the mainstay for lung cancer treatment, providing sustained therapeutic responses and improved prognosis compared with those obtained with surgery, chemotherapy, radiotherapy, and targeted therapy. It has the potential for anti-tumor treatment and killing tumor cells by activating human immunity and has moved the targets of anti-cancer therapy from malignant tumor cells to immune cell subsets. Two kinds of immune checkpoints, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1), are the main targets of current immunotherapy in lung cancer. Despite the successful outcomes achieved by immune checkpoint inhibitors, a small portion of lung cancer patients remain unresponsive to checkpoint immunotherapy or may ultimately become resistant to these agents as a result of the complex immune modulatory network in the tumor microenvironment. Therefore, it is imperative to exploit novel immunotherapy targets to further expand the proportion of patients benefiting from immunotherapy. This review summarizes the molecular features, biological function, and clinical significance of several novel checkpoints that have important roles in lung cancer immune responses beyond the CTLA-4 and PD-1/PD-L1 axes, including the markers of co-inhibitory and co-stimulatory T lymphocyte pathways and inhibitory markers of macrophages and natural killer cells.
简介:ImmunizationwithinactivatedautoreactiveTcells(Tcellvaccination)selectedfromindividual'sownTcellrepertoireprovidesauniqueinvivosettingfortestingimmuneregulationthatisknowntoinvolveinteractionsofavarietyofrelatedsurfacemolecules(1).ItinducesregulatoryimmuneresponsesthatcloselyresembletheinvivosituationwheretheimmunesystemischallengedbyclonalactivationandexpansionofgivenTcellpopulationsinvariousautoimmunediseases.TcellvaccinationprovidesapowerfulmeansofelicitingnaturalreactionsoftheimmunesysteminresponsetoclonalexpansionofTcells,whichcanusedasatherapeuticapproachtosuppressoreliminatespecificpathogenicautoreactiveTcellsinautoimmuneconditions.ClinicaltrialsusingTcellvaccinationtodepleteautoreactiveTcellsinhumanautoimmuneconditionshavebeguntorevealthepathologicrelevanceofvariousautoimmuneTcellpopulationsinthediseaseprocesses,providingauniqueopportunitytotesttheautoimmunetheoriesinaclinicalsetting.Cellular&MolecularImmunology.2004;1(5):321-327.
简介:IntravesicalBacillusCalmette-Guérin(BCG)haslongbeenthegoldstandardtreatmentofnonmuscleinvasivebladdercancer.Recently,therehasbeenanemergenceofnovelimmunotherapeuticagents,whichhaveshownpromiseinthetreatmentofurothelialcellcarcinoma.Theseagentsaimtoaugment,modify,orenhancetheimmuneresponse.SuchstrategiesincluderecombinantBCG,monoclonalantibodies,vaccines,genetherapy,andadoptiveT-celltherapy.Here,wereviewtheemergingimmunotherapeuticsinthetreatmentofnonmuscleinvasivebladdercancer.
简介:AbstractGastric cancer (GC) is one of the most common malignant tumors worldwide. Its incidence ranks the 5th among all malignant tumors globally, and it is the 3rd leading cause of death among patients with cancer. Surgical treatment is the first choice in clinical practice. However, targeted therapy, immunotherapy, and other treatment methods have also become research hotspots at home and abroad with the development of individualized precision therapy in recent years, besides traditional radiotherapy and chemotherapy. At present, targeted therapy and immunotherapy are methods used for treating GC, and they have important clinical application value and prospects. This study aimed to review the research progress of targeted therapy and immunotherapy for GC, focusing on its mechanism of action and related important clinical trials, hoping to provide references for the clinical treatment of GC.
简介:AbstractMalignant pleural mesothelioma (MPM) is a rare and aggressive malignant disease. Currently, the platinum doublet of pemetrexed and cisplatin is the standard first-line treatment for unresectable MPM. However, recent promising results of immunotherapy have markedly changed the landscape of MPM treatment. Further, the ongoing innovative therapeutic strategies are expected to expand the range of treatment options; however, several questions remain unanswered. First, establishing predictive biomarkers with high potency is urgently needed to optimize the patient selection process. Second, further exploration of the combination algorithm is expected to unveil more effective and safe regimens. Moreover, other dilemmas, such as the resistance mechanism of immunotherapy and the role of immunotherapy in perioperative settings, still warrant further exploration.
简介:Thecurrentconceptof“AdoptiveTCellImmunotherapyofCancer”isquitedifferentfromhowitwasoriginallyconceived.Withthedevelopmentofmoderntechnologyinmolecularbiology,cellbiology,immunologyandbiochemistryduringthelasttwentyyearsorso,adoptiveimmunotherapyhasgrownfromitsinitialformofasimple“bloodcelltransfer”intoitspresentprocesswhichinvolveshostvauccination,effectorcellactivation/polarizationandgeneticmodification.Withtheuseofimmuneadjuvantsandtheidentification/characterizationoftumor-reactiveTcellsubsets,orincombinationwithothertherapeuticstrategies,adoptivelytransferredTcellshavebecomemuchmorepotentinmediatingtumorregression.Inaddition,studiesonthetraffickingofinfusedTcells,celltransferperformedinlymphopenicmodels,aswellasthediscoveryofnoveltechniquesinimmunemonitoringforthegenerationofeffectorcellsinvitroandaftercelltransferinvivohaveprovidedusefultoolstofurtherimprovethetherapeuticefficacyofthisapproach.ThisarticlewillreviewtheserelatedaspectsofadoptiveTcellimmunotherapyofcancerwithspecificcommentsoncertaincriticalareasintheapplicationofthisapproach.Withtherapidlyevolvingadvancesinthisarea,itishopedthatthiscellularimmunologictherapyasitwasconceptualizedinthepast,canbecomemoreusefulinthetreatmentofhumancancerinthenearfuture.
简介:AbstractImmunotherapy has opened a new era in cancer treatment. Drugs represented by immune checkpoint inhibitors have led to important breakthroughs in the treatment of various solid tumors, greatly improving the survival rate of cancer patients. Many types of immunotherapeutic drugs have become widely available; however, their efficacy is variable, and relatively few patients with advanced cancer experience life-altering durable survival, reflecting the complex and highly regulated nature of the immune system. The research field of cancer immunotherapy (CIT) still faces many challenges in pursuing the broader social goal of "curing cancer." Increasing attention has been paid to strengthening the understanding of the molecular or cellular drivers of resistance to immunotherapy, actively exploring more effective therapeutic targets, and developing combination therapy strategies. Here, we review the key challenges that have emerged in the era of CIT and the possible solutions or development directions to overcome these difficulties, providing relevant references for basic research and the development of modified clinical treatment regimens.
简介:Personalizedcancermedicinehasseensignificantimprovementsoverthepastdecade.RecentElsevierconference:Miamiwintersymposium2015(MWS2015)'TowardsPersonalizedCancerMedicine'meetingwasdedicatedtothisexcitingfield,andfocusedonnewprogressinpersonalizeddrugdevelopmentandantibodydrugagainstcheckpointpathway.Thismeetingreportsummarizesthekeydevelopmentspresentedanddiscussedatthemeeting,withafocusonimmunotherapy,especiallyontheCTLA-4andPD-1/PD-L1pathways.Themonoclonalantibodydrugsinterveningthesecheckpointpathwayshavethepotentialtoplayalargerroleinpersonalizemedicinewithinthenearfuture.Hereweintendedtoprovideacomprehensivesummaryaboutongoingtrendsandfutureperspectivesonpersonalizedmedicineincancertherapy.
简介:AbstractThe tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is non-immunogenic, which consists of the stellate cells, fibroblasts, immune cells, extracellular matrix, and some other immune suppressive molecules. This low tumor perfusion microenvironment with physical dense fibrotic stroma shields PDAC from traditional antitumor therapies like chemotherapy and various strategies that have been proven successful in other types of cancer. Immunotherapy has the potential to treat minimal and residual diseases and prevent recurrence with minimal toxicity, and studies in patients with metastatic and nonresectable disease have shown some efficacy. In this review, we highlighted the main components of the pancreatic tumor microenvironment, and meanwhile, summarized the advances of some promising immunotherapies for PDAC, including checkpoint inhibitors, chimeric antigen receptors T cells, and cancer vaccines. Based on our previous researches, we specifically discussed how granulocyte-macrophage colony stimulating factor based pancreatic cancer vaccine prime the pancreatic tumor microenvironment, and introduced some novel immunoadjuvants, like the stimulator of interferon genes.
简介:AbstractHeat shock protein 96 (gp96) is a highly conserved protein in the endoplasmic reticulum. The functions of gp96 include promoting the oncogenesis and progression of glioma. In addition, tumor-derived gp96 can activate anti-tumor immune. Therefore, this protein was used to generate an anti-tumor vaccine and widely applied to glioma therapy. This review summarizes the mechanisms of gp96 in glioma oncogenesis and clinical trials of the gp96 tumor vaccine in glioma treatment.