Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy...Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.展开更多
The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(...The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.展开更多
基金National Key Research and Development Program,Grant/Award Number:2017YFSF090107National Natural Science Foundation of China,Grant/Award Numbers:82072996,81874131+1 种基金Hubei Province Natural Science Funds for Distinguished Young Scholar,Grant/Award Number:2017CFA062Innovative research team of high-level local universities in Shanghai,Grant/Award Number:ZLCX20180500。
文摘Cancer immunotherapy,especially immune checkpoint blockade(ICB),has revolutionized oncology.However,only a limited number of patients benefit from immunotherapy,and some cancers that initially respond to immunotherapy can ultimately relapse and progress.Thus,some studies have investigated combining immunotherapy with other therapies to overcome resistance to monotherapy.Recently,multiple preclinical and clinical studies have shown that tumor vasculature is a determinant of whether immunotherapy will elicit an antitumor response;thus,vascular targeting may be a promising strategy to improve cancer immunotherapy outcomes.A successful antitumor immune response requires an intact“Cancer-Immunity Cycle,”including T cell priming and activation,immune cell recruitment,and recognition and killing of cancer cells.Angiogenic inducers,especially vascular endothelial growth factor(VEGF),can interfere with activation,infiltration,and function of T cells,thus breaking the“Cancer-Immunity Cycle.”Together with immunostimulation-regulated tumor vessel remodeling,VEGF-mediated immunosuppression provides a solid therapeutic rationale for combining immunotherapy with antiangiogenic agents to treat solid tumors.Following the successes of recent landmark phase III clinical trials,therapies combining immune checkpoint inhibitors(ICIs)with antiangiogenic agents have become first-line treatments for multiple solid tumors,whereas the efficacy of such combinations in other solid tumors remains to be validated in ongoing studies.In this review,we discussed synergies between antiangiogenic agents and cancer immunotherapy based on results from preclinical and translational studies.Then,we discussed recent progress in randomized clinical trials.ICI-containing combinations were the focus of this review because of their recent successes,but combinations containing other immunotherapies were also discussed.Finally,we attempted to define critical challenges in combining ICIs with antiangiogenic agents to promote coordination and stimulate collaboration within the research community.
基金This work was supported by the National Natural Science Foundation of China(Nos.82072996(Z.J.S.)81874131(Z.J.S.)+1 种基金81702730(L.L.B.),and 51973076(G.Y.))the Fundamental Research Funds for the Central Universities(No.2042021kf0216)to Z.J.S.,China Postdoctoral Science Foundation(Nos.2018M630883 and 2019T120688)to L.L.B.,and Wuhan Young Medical Talents Training Project to L.L.B.
文摘The recurrence of head and neck squamous cell carcinoma(HNSCC)after surgical resection continues to pose a major challenge to cancer treatment.Advanced HNSCC exhibits a low response rate to immune checkpoint blockade(ICB),while photothermal therapy(PTT)can increase the infiltration of immune cells to make tumors more susceptible to cancer immunotherapy.In this regard,we designed and constructed a novel multifunctional nanocomposite comprised of oxidized bacterial cellulose(OBC),thrombin(TB),and gold nanocages(AuNCs)containing anti-programmed death 1(PD-1)antibody(αPD-1@AuNCs),which allows the combination of therapies with remarkable postoperative antitumor immunity to control local tumor recurrence.TheαPD-1@AuNCs displayed high light-to-heat conversion efficiency and induced pyroptosis under near infrared(NIR)irradiation,which activated a potent antitumor immune response.More importantly,the therapeutic system could induce tumor pyroptosis and enhance antitumor immune response by increasing T-cell infiltration and reducing the immune suppressive cells,when combined with local ICB therapy,which effectively avoided the tumor recurrence in a HNSCC postoperative mice model.Overall,the newly developed multifunctional nanocomposites could be a promising candidate for the treatment of postoperative HNSCC.
