The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive corr...The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.展开更多
P90 Ribosomal S6 Kinases(RSKs)constitute a class of Serine/Threonine(Ser/Thr)protein kinases and play a critical role as downstream targets in the Raf/MEK/ERK signaling pathway.Gaining insight into the biological func...P90 Ribosomal S6 Kinases(RSKs)constitute a class of Serine/Threonine(Ser/Thr)protein kinases and play a critical role as downstream targets in the Raf/MEK/ERK signaling pathway.Gaining insight into the biological function of RSK family proteins,given their functions in various tumors,is vital.The RSK family is involved in the regulation of cellular functions including cell proliferation,motility,invasion,and survival.The RSK family comprises four human isoforms(RSK1,RSK2,RSK3,and RSK4).The activation of RSK protein kinases is mediated through direct phosphorylation by extracellular signal-regulated kinase 1/2(ERK1/2)and phosphoinositide-dependent kinase 1(PDK1)after the Ras/MAPK(mitogen-activated protein kinase)pathway is activated.Recent evidence suggests that RSK family proteins promote the onset and metastasis of cancer,leading to the association of the protein expression of these kinases with various cancer types,such as colorectal cancer(CRC),breast cancer,lung cancer,kidney cancer,leukemia,esophageal squamous cell carcinoma,ovarian cancer,glioma,and endometrial cancer.In this review,we summarize the latest research on the RSK family,focusing on its role in patients with CRC,along with associated treatment challenges and limitations.This information enhances our comprehension of the regulation and function of RSK family proteins,highlighting their potential as both clinical biomarkers for diagnosing CRC and targets for molecular therapeutic interventions in the future.展开更多
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20190946Gusu Leading Talent Program for Innovation and Entrepreneurship,Grant/Award Number:ZXL2021441+5 种基金Suzhou health youth backbone talent“national tutorial system”training project,Grant/Award Number:Qngg2023005Key Research and Development Program of Social Development of Jiangsu Province,Grant/Award Number:BE2022725Natural Science Foundation of Anhui Province,Grant/Award Number:2308085QH281Beijing Sisko Clinical Oncology Research Foundation,Grant/Award Number:Y-tongshu2021/qn-0366Key Scientific Research Project of Colleges and Universities of Anhui Province of China,Grant/Award Number:2022AH050683National Natural Science Foundation of China,Grant/Award Numbers:12275003,32171382,32301169,U1932208。
文摘The immunological implications of cuproptosis,a form of cell death highly sensitive to oxygen presence,remain largely unexplored in the context of tumor immunother-apy.Herein,we initially investigate the positive correlation between cuproptosis and tumor immunotherapy through bioinformatics analysis.Subsequently,an oxygen generator loaded with copper ions(Cu/APH-M)has been constructed,which serves as an effective carrier of copper ions and crucially enhances the oxygenation of the tumor microenvironment.Importantly,Cu/APH-M-mediated dual strengthening of cuproptosis and radiotherapy could not only trigger a powerful antitumor immunity related to immunogenic cell death by RNA-sequencing analysis,but also effec-tively inhibit the growth of both distal and in situ low rectal tumors after combined immunotherapy,creating a robust immune memory effect.Our work reveals the ben-eficial effects of enhanced cuproptosis in radio-immunotherapy and elucidates its underlying mechanisms,which provides a novel approach for the synergistic inte-gration of cuproptosis with immunotherapy and radiotherapy,broadening the scope of cuproptosis-mediated tumor therapy.
基金supported by Suzhou Basic Research Key Project(No.SKY2023009),Suzhou health youth backbone talent“national tutorial system”training project(Qngg2023005)Beijing Xisike Clinical Oncology Research Foundation(Y-tongshu2021/qn-0366).
文摘P90 Ribosomal S6 Kinases(RSKs)constitute a class of Serine/Threonine(Ser/Thr)protein kinases and play a critical role as downstream targets in the Raf/MEK/ERK signaling pathway.Gaining insight into the biological function of RSK family proteins,given their functions in various tumors,is vital.The RSK family is involved in the regulation of cellular functions including cell proliferation,motility,invasion,and survival.The RSK family comprises four human isoforms(RSK1,RSK2,RSK3,and RSK4).The activation of RSK protein kinases is mediated through direct phosphorylation by extracellular signal-regulated kinase 1/2(ERK1/2)and phosphoinositide-dependent kinase 1(PDK1)after the Ras/MAPK(mitogen-activated protein kinase)pathway is activated.Recent evidence suggests that RSK family proteins promote the onset and metastasis of cancer,leading to the association of the protein expression of these kinases with various cancer types,such as colorectal cancer(CRC),breast cancer,lung cancer,kidney cancer,leukemia,esophageal squamous cell carcinoma,ovarian cancer,glioma,and endometrial cancer.In this review,we summarize the latest research on the RSK family,focusing on its role in patients with CRC,along with associated treatment challenges and limitations.This information enhances our comprehension of the regulation and function of RSK family proteins,highlighting their potential as both clinical biomarkers for diagnosing CRC and targets for molecular therapeutic interventions in the future.
