While immunotherapy with immune checkpoint inhibitors(ICIs)has revolutionized the clinical management of various malignancies,a large fraction of patients are refractory to ICIs employed as standalone therapeutics,nec...While immunotherapy with immune checkpoint inhibitors(ICIs)has revolutionized the clinical management of various malignancies,a large fraction of patients are refractory to ICIs employed as standalone therapeutics,necessitating the development of combinatorial treatment strategies.Immunogenic cell death(ICD)inducers have attracted considerable interest as combinatorial partners for ICIs,at least in part owing to their ability to initiate a tumor-targeting adaptive immune response.However,compared with either approach alone,combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity.Here,we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings,identify key factors that may explain discrepancies between preclinical and clinical findings,and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.展开更多
基金supported(as a PI unless otherwise indicated)by one R01 grant from the NIH/NCI(#CA271915)by two Breakthrough Level 2 grants from the US DoD BCRP(#BC180476P1,#BC210945)+11 种基金by a grant from the STARR Cancer Consortium(#I16--0064)by a Transformative Breast Cancer Consortium Grant from the US DoD BCRP(#W81XWH2120034,PI:Formenti)by a U54 grant from NIH/NCI(#CA274291)from the Leukemia and Lymphoma Society(LLS),by the 2019 Laura Ziskin Prize in Translational Research(#ZP--6177,PI:Formenti)from the Stand Up to Cancer(SU2C)by a Mantle Cell Lymphoma Research Initiative(MCL-RI,PI:Chen-Kiang)grant from the Leukemia and Lymphoma Society(LLS)by a Rapid Response Grant from the Functional Genomics Initiative(New York,US)by a pre-SPORE grant(PI:Demaria,Formenti)and a Clinical Trials Innovation Grant from the Sandra and Edward Meyer of Radiation Oncology at Weill Cornell Medicine(New York,US)and Fox Chase Cancer Center(Philadelphia,US)by industrial collaborations with Lytix Biopharma(Oslo,Norway),Promontory(New York,US)and Onxeo(Paris,France)by donations from Promontory(New York,US),the Luke Heller TECPR2 Foundation(Boston,US),Sotio a.s.(Prague,Czech Republic),Lytix Biopharma(Oslo,Norway),Onxeo(Paris,France),Ricerchiamo(Brescia,Italy),and Noxopharm(Chatswood,Australia)supported by the Flanders Research Foundation(FWO)and the Belgian National Fund for Scientific Research(F.R.S.-FNRS)under the Excellence of Science(EOS)program(#40007488),FWO grant(#G016221N)two Special Research Fund(BOF)grants from Ghent University(#BOF/IOP/2022/033,#BOF23/GOA/029)IOF“PULSE”grant(#F2023/IOF-ConcepTT/033)and IOF“IMMUNO-FER-GUARD”grant(#F2023/IOF-ConcepTT/106)from Ghent UniversityEC holds a Marie Sklodowska Curie(MSCA)postdoctoral fellowship(HORIZON-MSCA-2022 PF-01).
文摘While immunotherapy with immune checkpoint inhibitors(ICIs)has revolutionized the clinical management of various malignancies,a large fraction of patients are refractory to ICIs employed as standalone therapeutics,necessitating the development of combinatorial treatment strategies.Immunogenic cell death(ICD)inducers have attracted considerable interest as combinatorial partners for ICIs,at least in part owing to their ability to initiate a tumor-targeting adaptive immune response.However,compared with either approach alone,combinatorial regimens involving ICD inducers and ICIs have not always shown superior clinical activity.Here,we discuss accumulating evidence on the therapeutic interactions between ICD inducers and immunotherapy with ICIs in oncological settings,identify key factors that may explain discrepancies between preclinical and clinical findings,and propose strategies that address existing challenges to increase the efficacy of these combinations in patients with cancer.
