胰腺癌的免疫疗法——克服反应障碍
Immunotherapy in pancreatic adenocarcinoma-overcoming barriers to response.
作者信息
Rosenberg Ari, Mahalingam Devalingam
机构信息
Department of Medicine, Northwestern University, Chicago, IL, USA.
出版信息
J Gastrointest Oncol. 2018 Feb;9(1):143-159. doi: 10.21037/jgo.2018.01.13.
Abstract
Pancreatic adenocarcinoma (PAC) remains one of the leading causes of cancer-related death. Despite multiple advances in targeted and immune therapies, the 5-year survival in advanced PAC remains poor. In this review, we discuss some of the unique aspects of the tumor microenvironment (TME) in PAC that may contribute to its resistance to immune therapies, as well as opportunities to potentially overcome some of these inherent barriers. Furthermore, we discuss strategies to enable immune therapies in PAC such as cytotoxic chemotherapy and radiation therapy, cancer vaccines, cytokine based therapy, oncolytic viruses, and adoptive T-cell therapy. Finally, we address a variety of targeted therapies as a strategy to further amplify immune responses in PAC.
摘要
胰腺腺癌（PAC）仍然是癌症相关死亡的主要原因之一。尽管在靶向治疗和免疫治疗方面取得了多项进展，但晚期PAC的5年生存率仍然很低。在本综述中，我们讨论了PAC肿瘤微环境（TME）的一些独特方面，这些方面可能导致其对免疫治疗产生抗性，以及潜在克服其中一些固有障碍的机会。此外，我们还讨论了在PAC中实施免疫治疗的策略，如细胞毒性化疗和放射治疗、癌症疫苗、基于细胞因子的治疗、溶瘤病毒和过继性T细胞治疗。最后，我们探讨了各种靶向治疗方法，作为进一步增强PAC免疫反应的策略。
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本文引用的文献
1
Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study.
Oncologist. 2020 May;25(5):e808-e815. doi: 10.1634/theoncologist.2019-0473. Epub 2019 Nov 19.
2
Long-term survivors of pancreatic adenocarcinoma show low rates of genetic alterations in KRAS, TP53 and SMAD4.
Cancer Biomark. 2018 Feb 6;21(2):323-334. doi: 10.3233/CBM-170464.
3
CDK4/6 inhibition triggers anti-tumour immunity.
Nature. 2017 Aug 24;548(7668):471-475. doi: 10.1038/nature23465. Epub 2017 Aug 16.
4
TGF-β in pancreatic cancer initiation and progression: two sides of the same coin.
Cell Biosci. 2017 Aug 7;7:39. doi: 10.1186/s13578-017-0168-0. eCollection 2017.
5
Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy.
J Immunother Cancer. 2017 Jul 18;5(1):53. doi: 10.1186/s40425-017-0257-y.
6
Radiation therapy in the management of pancreatic adenocarcinoma: review of current evidence and future opportunities.
Chin Clin Oncol. 2017 Jun;6(3):28. doi: 10.21037/cco.2017.06.12.
7
Immunotherapy in pancreatic cancer: Unleash its potential through novel combinations.
World J Clin Oncol. 2017 Jun 10;8(3):230-240. doi: 10.5306/wjco.v8.i3.230.
8
A phase Ib study of pembrolizumab plus chemotherapy in patients with advanced cancer (PembroPlus).
Br J Cancer. 2017 Jun 27;117(1):33-40. doi: 10.1038/bjc.2017.145. Epub 2017 Jun 6.
9
Deploying Immunotherapy in Pancreatic Cancer: Defining Mechanisms of Response and Resistance.
Am Soc Clin Oncol Educ Book. 2017;37:267-278. doi: 10.1200/EDBK_175232.
10
Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy.
Pharmacol Ther. 2017 Nov;179:158-170. doi: 10.1016/j.pharmthera.2017.05.012. Epub 2017 May 23.
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