靶向肿瘤微环境治疗胰腺癌的新进展

张飞宇; 阿迪拉·亚克普; 赵金明; 高沿航

doi:10.3969/j.issn.1001-5256.2021.09.049

靶向肿瘤微环境治疗胰腺癌的新进展

DOI: 10.3969/j.issn.1001-5256.2021.09.049

吉林大学第一医院肝病科, 长春 130021

基金项目:

国家自然科学基金 (81972265);

吉林省自然科学基金 (20200201324JC)

利益冲突声明: 所有作者均声明不存在利益冲突。

作者贡献声明: 张飞宇负责选题, 收集分析资料, 撰写文章；阿迪拉·亚克普、赵金明参与选题, 收集资料；高沿航教授拟定写作思路, 指导撰写文章, 提供修改意见并最终定稿。

详细信息

通信作者:
高沿航, yanhang@mail.jlu.edu.cn

中图分类号: R735.9
计量
- 文章访问数: 615
- HTML全文浏览量: 172
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-23
- 录用日期: 2021-04-06
- 出版日期: 2021-09-20

New advances in the treatment of pancreatic cancer by targeting tumor microenvironment

Department of Hepatology, The First Hospital of Jilin University, Changchun 130021, China

Research funding:

National Natural Science Foundation of China (81972265);

Natural Science Foundation of Jilin Province (20200201324JC)

摘要

摘要: 胰腺癌是5年生存率最低的消化道恶性肿瘤, 现有的一线治疗方案并未明显改善患者总体预后, 因此需要探索新的治疗方式。胰腺癌肿瘤微环境如基质屏障、免疫微环境、外泌体在促进胰腺癌细胞增殖、浸润、转移及放化疗抵抗中起到重要作用。总结了与胰腺癌肿瘤微环境相关的潜在靶点及其临床进展, 以期为胰腺癌治疗提供新思考。
- 胰腺肿瘤 /
- 肿瘤微环境 /
- 免疫疗法
Abstract: Pancreatic cancer is the malignant tumor of the digestive tract with the lowest 5-year survival rate, and current first-line treatment regimens cannot significantly improve the overall prognosis of patients, so it is necessary to explore new treatment methods. A large number of studies have shown that the tumor microenvironment of pancreatic cancer, such as stromal barrier, immune microenvironment, and exosomes, plays an important role in promoting the proliferation, invasion, metastasis, and chemoradiotherapy resistance of pancreatic cancer cells. This article summarizes the potential targets associated with the tumor microenvironment of pancreatic cancer and related clinical research advances, in order to provide new ideas for the treatment of pancreatic cancer.
- Pancreatic Neoplasms /
- Tumor Microenvironment /
- Immunotherapy

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参考文献(24)

[1]	SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590.
[2]	SUNG H, FERLAY J, SIEGEL RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. DOI: 10.3322/caac.21660.
[3]	CHEN IM, WILLUMSEN N, DEHLENDORFF C, et al. Clinical value of serum hyaluronan and propeptide of type Ⅲ collagen in patients with pancreatic cancer[J]. Int J Cancer, 2020, 146(10): 2913-2922. DOI: 10.1002/ijc.32751.
[4]	DALIN S, SULLIVAN MR, LAU AN, et al. Deoxycytidine release from pancreatic stellate cells promotes gemcitabine resistance[J]. Cancer Res, 2019, 79(22): 5723-5733. DOI: 10.1158/0008-5472.CAN-19-0960.
[5]	ÖHLUND D, HANDLY-SANTANA A, BIFFI G, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer[J]. J Exp Med, 2017, 214(3): 579-596. DOI: 10.1084/jem.20162024.
[6]	GOEHRIG D, NIGRI J, SAMAIN R, et al. Stromal protein βig-h3 reprogrammes tumour microenvironment in pancreatic cancer[J]. Gut, 2019, 68(4): 693-707. DOI: 10.1136/gutjnl-2018-317570.
[7]	YU M, GUAN R, HONG W, et al. Prognostic value of tumor-associated macrophages in pancreatic cancer: A meta-analysis[J]. Cancer Manag Res, 2019, 11: 4041-4058. DOI: 10.2147/CMAR.S196951.
[8]	HENZE J, TACKE F, HARDT O, et al. Enhancing the efficacy of CAR T cells in the tumor microenvironment of pancreatic cancer[J]. Cancers (Basel), 2020, 12(6): 1389. DOI: 10.3390/cancers12061389.
[9]	YIN Z, MA T, HUANG B, et al. Macrophage-derived exosomal microRNA-501-3p promotes progression of pancreatic ductal adenocarcinoma through the TGFBR3-mediated TGF-β signaling pathway[J]. J Exp Clin Cancer Res, 2019, 38(1): 310. DOI: 10.1186/s13046-019-1313-x.
[10]	RICHARDS KE, ZELENIAK AE, FISHEL ML, et al. Cancer-associated fibroblast exosomes regulate survival and proliferation of pancreatic cancer cells[J]. Oncogene, 2017, 36(13): 1770-1778. DOI: 10.1038/onc.2016.353.
[11]	RAMANATHAN RK, MCDONOUGH SL, PHILIP PA, et al. Phase IB/Ⅱ randomized study of FOLFIRINOX plus pegylated recombinant human hyaluronidase versus FOLFIRINOX alone in patients with metastatic pancreatic adenocarcinoma: SWOG S1313[J]. J Clin Oncol, 2019, 37(13): 1062-1069. DOI: 10.1200/JCO.18.01295.
[12]	van CUTSEM E, TEMPERO MA, SIGAL D, et al. Randomized phase Ⅲ trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine for patients with hyaluronan-high metastatic pancreatic adenocarcinoma[J]. J Clin Oncol, 2020, 38(27): 3185-3194. DOI: 10.1200/JCO.20.00590.
[13]	CHEN X, ZHOU W, LIANG C, et al. Codelivery nanosystem targeting the deep microenvironment of pancreatic cancer[J]. Nano Lett, 2019, 19(6): 3527-3534. DOI: 10.1021/acs.nanolett.9b00374.
[14]	HAN X, LI Y, XU Y, et al. Reversal of pancreatic desmoplasia by re-educating stellate cells with a tumour microenvironment-activated nanosystem[J]. Nat Commun, 2018, 9(1): 3390. DOI: 10.1038/s41467-018-05906-x.
[15]	MIZUTANI Y, KOBAYASHI H, ⅡDA T, et al. Meflin-positive cancer-associated fibroblasts inhibit pancreatic carcinogenesis[J]. Cancer Res, 2019, 79(20): 5367-5381. DOI: 10.1158/0008-5472.CAN-19-0454.
[16]	O'REILLY EM, OH DY, DHANI N, et al. Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: A phase 2 randomized clinical trial[J]. JAMA Oncol, 2019, 5(10): 1431-1438. DOI: 10.1001/jamaoncol.2019.1588.
[17]	ZAMARIN D, HAMID O, NAYAK-KAPOOR A, et al. Mogamulizumab in combination with durvalumab or tremelimumab in patients with advanced solid tumors: A phase I study[J]. Clin Cancer Res, 2020, 26(17): 4531-4541. DOI: 10.1158/1078-0432.CCR-20-0328.
[18]	TEMPERO M, OH D, MACARULLA T, et al. O-002 - Ibrutinib in combination with nab-paclitaxel and gemcitabine as first-line treatment for patients with metastatic pancreatic adenocarcinoma: Results from the phase 3 RESOLVE study[J]. Ann Oncol, 2019, 30: iv126. DOI: 10.1093/annonc/mdz154.001.
[19]	MA HS, POUDEL B, TORRES ER, et al. A CD40 agonist and PD-1 antagonist antibody reprogram the microenvironment of nonimmunogenic tumors to allow T-cell-mediated anticancer activity[J]. Cancer Immunol Res, 2019, 7(3): 428-442. DOI: 10.1158/2326-6066.CIR-18-0061.
[20]	DU H, HIRABAYASHI K, AHN S, et al. Antitumor responses in the absence of toxicity in solid tumors by targeting B7-H3 via chimeric antigen receptor T cells[J]. Cancer Cell, 2019, 35(2): 221-237. e8. DOI: 10.1016/j.ccell.2019.01.002.
[21]	YAZDANIFAR M, ZHOU R, GROVER P, et al. Overcoming immunological resistance enhances the efficacy of a novel anti-tMUC1-CAR T cell treatment against pancreatic ductal inoma[J]. Cells, 2019, 8(9): 1070. DOI: 10.3390/cells8091070.
[22]	XIE YJ, DOUGAN M, JAILKHANI N, et al. Nanobody-based CAR T cells that target the tumor microenvironment inhibit the growth of solid tumors in immunocompetent mice[J]. Proc Natl Acad Sci U S A, 2019, 116(16): 7624-7631. DOI: 10.1073/pnas.1817147116.
[23]	MA L, DICHWALKAR T, CHANG J, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor[J]. Science, 2019, 365(6449): 162-168. DOI: 10.1126/science.aav8692.
[24]	ZHOU W, ZHOU Y, CHEN X, et al. Pancreatic cancer-targeting exosomes for enhancing immunotherapy and reprogramming tumor microenvironment[J]. Biomaterials, 2021, 268: 120546. DOI: 10.1016/j.biomaterials.2020.120546.