
浏览全部资源
扫码关注微信
兰州大学第一临床医学院,兰州 730030
王 虎,Email:wanghu20@lzu.edu.cn,研究方向:肝胆胰外科。
朱克祥,Email:flexzhu6910@126.com。
收稿:2023-10-18,
修回:2023-12-11,
录用:2023-12-15,
纸质出版:2024-03-28
移动端阅览
王虎,尹艳梅,李婧,等.胰腺导管腺癌免疫检查点阻断耐药的生物标志物和治疗选择[J].重庆医科大学学报,2024,49(3):242-245.
Wang Hu,Yin Yanmei,Li Jing,et al.Biomarkers and treatment options for immune checkpoint blockade resistance in pancreatic ductal adenocarcinoma[J].Journal of Chongqing Medical University,2024,49(3):242-245.
王虎,尹艳梅,李婧,等.胰腺导管腺癌免疫检查点阻断耐药的生物标志物和治疗选择[J].重庆医科大学学报,2024,49(3):242-245. DOI: 10.13406/j.cnki.cyxb.003440.
Wang Hu,Yin Yanmei,Li Jing,et al.Biomarkers and treatment options for immune checkpoint blockade resistance in pancreatic ductal adenocarcinoma[J].Journal of Chongqing Medical University,2024,49(3):242-245. DOI: 10.13406/j.cnki.cyxb.003440.
免疫检查点阻断(immune checkpoint blockade,ICB)的单药治疗在胰腺导管腺癌(pancreatic ductal adenocarcinoma,PDAC)中未见成效,采取合理的联合疗法是克服PDAC ICB抵抗的有效策略。目前为克服PDAC ICB耐药的联合手段主要包括增强PDAC表面的程序性死亡受体-配体1(programmed cell death-ligand 1,PD-L1)或组织相容性复合体Ⅰ(histocompatibility complex Ⅰ,MHC-Ⅰ);靶向免疫细胞中发挥抑制功能的关键效应因子,改善PDAC的免疫抑制微环境;联合能量消融、光动力疗法、纳米材料包裹等手段促进肿瘤相关抗原的释放,刺激免疫激活。本综述旨在对近年PDAC中发现的ICB耐药靶标和新兴手段进行梳理,为克服PDAC ICB耐药提供新思路。
Monotherapy for immune checkpoint blockade(ICB) lacks efficacy in pancreatic ductal adenocarcinoma(PDAC),and rational combination therapy is an effective strategy to overcome ICB resistance in PDAC. Currently,combination therapies to overcome ICB resistance in PDAC mainly include the following:enhanced expression of programmed death receptor-ligand 1 or histocompatibility complex Ⅰ on the surface of PDAC cells;targeting key effectors in immune cells that play an immunosuppressive function to improve the immunosuppressive microenvironment of PDAC;combining the methods such as energy ablation,photodynamic therapy,and nano-material encapsulation to promote the release of tumor-associated antigens and stimulate immune activation. This article reviews the targets for ICB resistance and emerging methods in PDAC in recent years,so as to provide new ideas to address ICB resistance in PDAC.
Siegel RL , Miller KD , Fuchs HE , et al . Cancer statistics,2021 [J ] . CA a Cancer J Clin , 2021 , 71 ( 1 ): 7 - 33 .
McGuigan A , Kelly P , Turkington RC , et al . Pancreatic cancer:a review of clinical diagnosis,epidemiology,treatment and outcomes [J ] . World J Gastroenterol , 2018 , 24 ( 43 ): 4846 - 4861 .
von Hoff DD , Ervin T , Arena FP , et al . Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine [J ] . N Engl J Med , 2013 , 369 ( 18 ): 1691 - 1703 .
Harrington KJ , Ferris RL , Jr Blumenschein G , et al . Nivolumab versus standard,single-agent therapy of investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141):health-related quality-of-life results from a randomised,phase 3 trial [J ] . Lancet Oncol , 2017 , 18 ( 8 ): 1104 - 1115 .
Reck M , Rodríguez-Abreu D , Robinson AG , et al . Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer [J ] . N Engl J Med , 2016 , 375 ( 19 ): 1823 - 1833 .
Robert C , Schachter J , Long GV , et al . Pembrolizumab versus ipilimumab in advanced melanoma [J ] . N Engl J Med , 2015 , 372 ( 26 ): 2521 - 2532 .
Riquelme E , Maitra A , McAllister F . Immunotherapy for pancreatic cancer:more than just a gut feeling [J ] . Cancer Discov , 2018 , 8 ( 4 ): 386 - 388 .
Zhang ZZ , Cheng LJ , Li J , et al . Targeting Plk1 sensitizes pancreatic cancer to immune checkpoint therapy [J ] . Cancer Res , 2022 , 82 ( 19 ): 3532 - 3548 .
Zhang YQ , Velez-Delgado A , Mathew E , et al . Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer [J ] . Gut , 2017 , 66 ( 1 ): 124 - 136 .
Somani VK , Zhang DX , Dodhiawala PB , et al . IRAK4 signaling drives resistance to checkpoint immunotherapy in pancreatic ductal adenocarcinoma [J ] . Gastroenterology , 2022 , 162 ( 7 ): 2047 - 2062 .
Deng YL , Xia XH , Zhao Y , et al . Glucocorticoid receptor regulates PD-L1 and MHC-I in pancreatic cancer cells to promote immune evasion and immunotherapy resistance [J ] . Nat Commun , 2021 , 12 ( 1 ): 7041 .
Liu J , Kang R , Kroemer G , et al . Targeting HSP90 sensitizes pancreas carcinoma to PD-1 blockade [J ] . Oncoimmunology , 2022 , 11 ( 1 ): 2068488 .
Yamamoto K , Venida A , Perera RM , et al . Selective autophagy of MHC-I promotes immune evasion of pancreatic cancer [J ] . Autophagy , 2020 , 16 ( 8 ): 1524 - 1525 .
Hu GF , He N , Cai CQ , et al . HDAC3 modulates cancer immunity via increasing PD-L1 expression in pancreatic cancer [J ] . Pancreatology , 2019 , 19 ( 2 ): 383 - 389 .
Zhou YK , Jin X , Yu HX , et al . HDAC5 modulates PD-L1 expression and cancer immunity via p65 deacetylation in pancreatic cancer [J ] . Theranostics , 2022 , 12 ( 5 ): 2080 - 2094 .
Lin ZQ , Huang KK , Guo H , et al . Targeting ZDHHC9 potentiates anti-programmed death-ligand 1 immunotherapy of pancreatic cancer by modifying the tumor microenvironment [J ] . Biomedecine Pharmacother , 2023 , 161 : 114567 .
Ravindranathan S , Passang T , Li JM , et al . Targeting vasoactive intestinal peptide-mediated signaling enhances response to immune checkpoint therapy in pancreatic ductal adenocarcinoma [J ] . Nat Commun , 2022 , 13 ( 1 ): 6418 .
Gulhati P , Schalck A , Jiang S , et al . Targeting T cell checkpoints 41BB and LAG3 and myeloid cell CXCR1/CXCR2 results in antitumor immunity and durable response in pancreatic cancer [J ] . Nat Cancer , 2023 , 4 ( 1 ): 62 - 80 .
Zhu Y , Knolhoff BL , Meyer MA , et al . CSF 1 /CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models [J ] . Cancer Res , 2014 , 74 ( 18 ): 5057 - 5069 .
Panni RZ , Herndon JM , Zuo C , et al . Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies [J ] . Sci Transl Med , 2019 , 11 ( 499 ): eaau9240 .
Ager CR , Boda A , Rajapakshe K , et al . High potency STING agonists engage unique myeloid pathways to reverse pancreatic cancer immune privilege [J ] . J Immunother Cancer , 2021 , 9 ( 8 ): e003246 .
Wang JX , Saung MT , Li KY , et al . CCR2/CCR5 inhibitor permits the radiation-induced effector T cell infiltration in pancreatic adenocarcinoma [J ] . J Exp Med , 2022 , 219 ( 5 ): e20211631 .
Garcia Garcia CJ , Huang YQ , Fuentes NR , et al . Stromal HIF 2 regulates immune suppression in the pancreatic cancer microenvironment [J ] . Gastroenterology , 2022 , 162 ( 7 ): 2018 - 2031 .
Koikawa K , Kibe S , Suizu F , et al . Targeting Pin1 renders pancreatic cancer eradicable by synergizing with immunochemotherapy [J ] . Cell , 2021 , 184 ( 18 ): 4753 - 4771 .
Dominguez CX , Müller S , Keerthivasan S , et al . Single-cell RNA sequencing reveals stromal evolution into LRRC15 + myofibroblasts as a determinant of patient response to cancer immunotherapy [J ] . Cancer Discov , 2020 , 10 ( 2 ): 232 - 253 .
Lopez-Yrigoyen M , Cassetta L , Pollard JW . Macrophage targeting in cancer [J ] . Ann N Y Acad Sci , 2021 , 1499 ( 1 ): 18 - 41 .
Dixit A , Sarver A , Zettervall J , et al . Targeting TNF-α-producing macrophages activates antitumor immunity in pancreatic cancer via IL-33 signaling [J ] . JCI Insight , 2022 , 7 ( 22 ): e153242 .
Quaranta V , Rainer C , Nielsen SR , et al . Macrophage-derived granulin drives resistance to immune checkpoint inhibition in metastatic pancreatic cancer [J ] . Cancer Res , 2018 , 78 ( 15 ): 4253 - 4269 .
Wang W , Marinis JM , Beal AM , et al . RIP1 kinase drives macrophage-mediated adaptive immune tolerance in pancreatic cancer [J ] . Cancer Cell , 2020 , 38 ( 4 ): 585 - 590 .
Zhang Y , Chandra V , Riquelme Sanchez E , et al . Interleukin-17-induced neutrophil extracellular traps mediate resistance to checkpoint blockade in pancreatic cancer [J ] . J Exp Med , 2020 , 217 ( 12 ): e20190354 .
Cappellesso F , Orban MP , Shirgaonkar N , et al . Targeting the bicarbonate transporter SLC4A4 overcomes immunosuppression and immunotherapy resistance in pancreatic cancer [J ] . Nat Cancer , 2022 , 3 ( 12 ): 1464 - 1483 .
Osborne N , Sundseth R , Burks J , et al . Gastrin vaccine improves response to immune checkpoint antibody in murine pancreatic cancer by altering the tumor microenvironment [J ] . Cancer Immunol Immunother , 2019 , 68 ( 10 ): 1635 - 1648 .
Zhang ZF , Yang AN , Chaurasiya S , et al . CF33-hNIS-antiPDL1 virus primes pancreatic ductal adenocarcinoma for enhanced anti-PD-L1 therapy [J ] . Cancer Gene Ther , 2022 , 29 ( 6 ): 722 - 733 .
Tichet M , Wullschleger S , Chryplewicz A , et al . Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8 + Tcells and reprogramming macrophages [J ] . Immunity , 2023 , 56 ( 1 ): 162 - 179 .
Faraoni EY , O’Brien BJ , Strickland LN , et al . Radiofrequency ablation remodels the tumor microenvironment and promotes neutrophil-mediated abscopal immunomodulation in pancreatic cancer [J ] . Cancer Immunol Res , 2023 , 11 ( 1 ): 4 - 12 .
Zhang Q , Green MD , Lang XT , et al . Inhibition of ATM increases interferon signaling and sensitizes pancreatic cancer to immune checkpoint blockade therapy [J ] . Cancer Res , 2019 , 79 ( 15 ): 3940 - 3951 .
Zhao J , Wen XF , Tian L , et al . Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer [J ] . Nat Commun , 2019 , 10 ( 1 ): 899 .
Sun F , Zhu QR , Li TL , et al . Regulating glucose metabolism with prodrug nanoparticles for promoting photoimmunotherapy of pancreatic cancer [J ] . Adv Sci , 2021 , 8 ( 4 ): 2002746 .
Zhao J , Xiao ZL , Li TT , et al . Stromal modulation reverses primary resistance to immune checkpoint blockade in pancreatic cancer [J ] . ACS Nano , 2018 , 12 ( 10 ): 9881 - 9893 .
0
浏览量
13
下载量
0
CSCD
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621