胰腺导管腺癌免疫治疗研究现状和展望

doi:10.11904/j.issn.1002-3070.2022.06.003

实用肿瘤学杂志 ›› 2022, Vol. 36 ›› Issue (6): 502-506.doi: 10.11904/j.issn.1002-3070.2022.06.003

• 消化道肿瘤免疫治疗专题 • 上一篇下一篇

胰腺导管腺癌免疫治疗研究现状和展望

巩芮宁（综述）, 任贺（审校）

青岛大学附属医院消化内科;消化道肿瘤诊断和治疗中心;肿瘤免疫和细胞治疗中心;医学研究中心(青岛 266003)

收稿日期:2022-01-10 修回日期:2022-08-10 出版日期:2022-12-28 发布日期:2023-01-06
通讯作者: 任贺,E-mail:herenrh@163.com
作者简介:巩芮宁,女,(1991-),博士研究生,从事胰腺癌发生发展的免疫学研究
基金资助:
国家杰出青年科学基金(编号:82125026);“泰山学者”人才专项(编号:Ts20190987);山东省自然科学基金重大基础研究项目(编号:ZR2020ZD11)

Research progress and prospect of immunotherapy for pancreatic ductal adenocarcinoma

GONG Ruining, REN He

Department of Gastroenterology,The Affiliated Hospital of Qingdao University;Center for Gastrointestinal Cancer Diagnosis and Treatment;Tumor Immunology and Cytotherapy;Medical Research Center,Qingdao 266003,China

Received:2022-01-10 Revised:2022-08-10 Online:2022-12-28 Published:2023-01-06

摘要/Abstract

摘要： 胰腺导管腺癌(Pancreatic ductal adenocarcinoma,PDAC)是胰腺癌最常见的类型,预后极差。手术切除是目前唯一的根治手段,但多数患者就诊时已失去手术机会。免疫治疗作为一种新兴的治疗手段,在多种实体瘤和血液系统恶性肿瘤治疗中显现出乐观前景。然而,PDAC肿瘤抗原性低以及免疫抑制微环境等特征导致其免疫治疗困难重重。本文通过综述PDAC的肿瘤微环境组成特点和目前开展的新型免疫治疗策略,为PDAC的免疫治疗研究提供新思路。

关键词: 胰腺导管腺癌, 免疫微环境, 免疫治疗, 免疫逃逸

Abstract: Pancreatic ductal adenocarcinoma(PDAC)is the most common type of pancreatic cancer,and the prognosis is extremely poor.Surgical resection is the only radical cure at present,but most patients have lost the chance of surgery when they seek medical adviee.As an emerging treatment,immunotherapy shows promising prospects in the treatment of various solid tumors and hematological malignancies.However,the low antigenicity and the immunosuppressive microenvironment of PDAC make its immunotherapy difficult.This article provides new ideas for the immunotherapy research of PDAC by reviewing the characteristics of the tumor microenvironment composition of PDAC and the current novel immunotherapy strategies.

Key words: Pancreatic ductal adenocarcinoma, Immune microenvironment, Immunotherapy, Immune evasion

中图分类号:

R735.9

巩芮宁, 任贺. 胰腺导管腺癌免疫治疗研究现状和展望[J]. 实用肿瘤学杂志, 2022, 36(6): 502-506.

GONG Ruining, REN He. Research progress and prospect of immunotherapy for pancreatic ductal adenocarcinoma[J]. Journal of Practical Oncology, 2022, 36(6): 502-506.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2022.06.003

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2022/V36/I6/502

参考文献

1 Wolfgang CL,Herman JM,Laheru DA,et al.Recent progress in pancreatic cancer[J].CA Cancer J Clin,2013,63(5):318-348.
2 Conroy T,Hammel P,Hebbar M,et al.FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer[J].N Engl J Med,2018,379(25):2395-2406.
3 Ohue Y,Nishikawa H.Regulatory T(Treg)cells in cancer:Can treg cells be a new therapeutic target?[J].Cancer Sci,2019,110(7):2080-2089.
4 Wang X,Lang M,Zhao T,et al.Cancer-FOXP3 directly activated CCL5 to recruit FOXP3⁺Treg cells in pancreatic ductal adenocarcinoma[J].Oncogene,2017,36(21):3048-3058.
5 Houchen CW,Li M.A subset of epithelial cells mimics regulatory T cells and contributes to immune evasion during development of pancreatic adenocarcinoma[J].BMC Med,2020,18(1):155.
6 Pylayeva-Gupta Y,Lee KE,Hajdu CH,et al.Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia[J].Cancer Cell,2012,21(6):836-847.
7 Gabrilovich DI.Myeloid-Derived suppressor cells[J].Cancer Immunol Res,2017,5(1):3-8.
8 Schmieder A,Michel J,Schnhaar K,et al.Differentiation and gene expression profile of tumor-associated macrophages[J].Semin Cancer Biol,2012,22(4):289-297.
9 Tanaka A,Sakaguchi S.Regulatory T cells in cancer immunotherapy[J].Cell Res,2017,27(1):109-118.
10 Steele CW,Karim SA,Leach JDG,et al.CXCR2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma[J].Cancer Cell,2016,29(6):832-845.
11 Liu J,Jiang W,Zhao K,et al.Tumoral EHF predicts the efficacy of anti-PD1 therapy in pancreatic ductal adenocarcinoma[J].J Exp Med,2019,216(3):656-673.
12 Sharma MD,Baban B,Chandler P,et al.Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase[J].J Clin Invest,2007,117(9):2570-2582.
13 Sanford DE,Belt BA,Panni RZ,et al.Inflammatory monocyte mobilization decreases patient survival in pancreatic cancer:a role for targeting the CCL2/CCR2 axis[J].Clin Cancer Res,2013,19(13):3404-3415.
14 Seo YD,Pillarisetty VG.T-cell programming in pancreatic adenocarcinoma:a review[J].Cancer Gene Ther,2017,24(3):106-113.
15 Morita T,Kodama Y,Shiokawa M,et al.CXCR4 in tumor epithelial cells mediates desmoplastic reaction in pancreatic ductal adenocarcinoma[J].Cancer Res,2020,80(19):4058-4070.
16 Johnson BA 3rd,Yarchoan M,Lee V,et al.Strategies for increasing pancreatic tumor immunogenicity[J].Clin Cancer Res,2017,23(7):1656-1669.
17 Mace TA,Shakya R,Pitarresi JR,et al.IL-6 and PD-L1 antibody blockade combination therapy reduces tumour progression in murine models of pancreatic cancer[J].Gut,2018,67(2):320-332.
18 Hu F,Guo F,Zhu Y,et al.IL-17 in pancreatic disease:pathogenesis and pharmacotherapy[J].Am J Cancer Res,2020,10(11):3551-3564.
19 Brower V.Checkpoint blockade immunotherapy for cancer comes of age[J].J Natl Cancer Inst,2015,107(3):69.
20 Iwai Y,Hamanishi J,Chamoto K,et al.Cancer immunotherapies targeting the PD-1 signaling pathway[J].J Biomed Sci,2017,24(1):26.
21 Royal RE,Levy C,Turner K,et al.Phase 2 trial of single agent Ipilimumab(anti-CTLA-4)for locally advanced or metastatic pancreatic adenocarcinoma[J].J Immunother,2010,33(8):828-833.
22 Padrón LJ,Maurer DM,O′Hara MH,et al.Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer:clinical and immunologic analyses from the randomized phase 2 PRINCE trial[J].Nat Med,2022,28(6):1167-1177.
23 Wang Y,Zheng K,Xiong H,et al.PARP inhibitor upregulates PD-L1 expression and provides a new combination therapy in pancreatic cancer[J].Front Immunol,2021,12:762989.
24 Aida K,Miyakawa R,Suzuki K,et al.Suppression of Tregs by anti-glucocorticoid induced TNF receptor antibody enhances the antitumor immunity of interferon-α gene therapy for pancreatic cancer[J].Cancer Sci,2014,105(2):159-167.
25 Stanley ER,Chitu V.CSF-1 receptor signaling in myeloid cells[J].Cold Spring Harb Perspect Biol,2014,6(6):21857.
26 MacDonald KP,Palmer JS,Cronau S,et al.An antibody against the colony-stimulating factor 1 receptor depletes the resident subset of monocytes and tissue and tumor-associated macrophages but does not inhibit inflammation[J].Blood,2010,116(19):3955-3963.
27 Zhu Y,Yang J,Xu D,et al.Disruption of tumour-associated macrophage trafficking by the osteopontin-induced colony-stimulating factor-1 signalling sensitises hepatocellular carcinoma to anti-PD-L1 blockade[J].Gut,2019,68(9):1653-1666.
28 Klichinsky M,Ruella M,Shestova O,et al.Human chimeric antigen receptor macrophages for cancer immunotherapy[J].Nat Biotechnol,2020,38(8):947-953.
29 Bockorny B,Semenisty V,Macarulla T,et al.BL-8040,a CXCR4 antagonist,in combination with pembrolizumab and chemotherapy for pancreatic cancer:the COMBAT trial[J].Nat Med,2020,26(6):878-885.
30 Wang X,Li X,Wei X,et al.PD-L1 is a direct target of cancer-FOXP3 in pancreatic ductal adenocarcinoma(PDAC),and combined immunotherapy with antibodies against PD-L1 and CCL5 is effective in the treatment of PDAC[J].Signal Transduct Target Ther,2020,5(1):38.
31 Manuel ER,Chen J,D′Apuzzo M,et al.Salmonella-Based therapy targeting undoleamine 2,3-Dioxygenase coupled with enzymatic depletion of tumor hyaluronan induces complete regression of aggressive pancreatic tumors[J].Cancer Immunol Res,2015,3(9):1096-1107.
32 Bahary N,Garrido-Laguna I.Phase 2 trial of the indoleamine 2,3-dioxygenase pathway(IDO)inhibitor indoximod plus gemcitabine/nab-paclitaxel for the treatment of metastatic pancreas cancer:interim analysis[J].Journal Clinical Oncology,2016,34(15):3020.
33 Hall M,Liu H,Malafa M,et al.Expansion of tumor-infiltrating lymphocytes(TIL)from human pancreatic tumors[J].J Immunother Cancer,2016,4:61.
34 Poschke I,Faryna M,Bergmann F,et al.Identification of a tumor-reactive T-cell repertoire in the immune infiltrate of patients with resectable pancreatic ductal adenocarcinoma[J].Oncoimmunology,2016,5(12):e1240859.

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胰腺导管腺癌免疫治疗研究现状和展望

Research progress and prospect of immunotherapy for pancreatic ductal adenocarcinoma

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