胆管癌免疫治疗的研究进展

秀洋 曹(华北理工大学研究生院，中国)
大旭 彭(华北理工大学研究生院，中国)

摘要

胆管癌（cholangiocarcinoma）是一种侵袭性恶性肿瘤，发生率较低，但其恶性程度高，且治疗方案有限，预后差，所以需要新的治疗方法。近年来，免疫治疗已成为肿瘤领域的研究热点，它利用患者原有的免疫系统靶向杀伤肿瘤细胞，这种治疗方法在恶性黑色素瘤和晚期非小细胞肺癌中已经取得了令人欣喜的治疗效果。中国和国际上对于胆管癌免疫治疗的新方法也正在进行积极的探索，部分研究在早期实验中也取得了积极的结果。因此，免疫治疗在胆管癌中的应用价值得到了初步证实，值得进一步研究。目前，中国和国际上针对胆管癌的免疫治疗方法主要包括通过肽和树突状细胞疫苗进行靶向肿瘤抗原治疗、同种异体细胞过继免疫治疗以及免疫检测点抑制剂治疗。论文从肿瘤的宿主免疫反应、肿瘤疫苗、过继性T细胞治疗和免疫检测点抑制剂治疗四个方面对其在胆管癌治疗中的研究进展作一综述

关键词

胆管癌；免疫治疗；研究进展

参考

管梅,白春梅.胆道系统肿瘤的药物治疗[J].协和医学杂志,2020

(03):325-333.

Eckel F, Schmid R M. Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials[J]. Chemotherapy, 2014(01):13-23.

Raval R R, Sharabi A B, Walker A J, et al. Tumor immunology and cancer immunotherapy: summary of the 2013 SITC primer[J]. J Immunother Cancer, 2014(02):14.

Velcheti V, Schalper K. Basic Overview of Current Immunotherapy Approaches in Cancer[J]. Am Soc Clin Oncol Educ Book, 2016(35):298-308.

Zheng L, Xue J, Jaffee E M, et al. Role of immune cells and immune-based therapies in pancreatitis and pancreatic ductal adenocarcinoma[J]. Gastroenterology, 2013(06):1230-1240.

Oshikiri T, Miyamoto M, Shichinohe T, et al. Prognostic value of intratumoral CD8+ T lymphocyte in extrahepatic bile duct carcinoma as essential immune response[J]. J Surg Oncol, 2003(04):224-228.

Goeppert B, Frauenschuh L, Zucknick M, et al. Prognostic impact of tumour-infiltrating immune cells on biliary tract cancer[J]. Br J Cancer, 2013(10):2665-74.

Rimassa L, Personeni N, Aghemo A, et al. The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine[J]. J Autoimmun, 2019(100):17-26.

Nakatsuka S, Oji Y, Horiuchi T, et al. Immunohistochemical detection of WT1 protein in a variety of cancer cells[J]. Mod Pathol, 2006(06):804-814.

Qi X W, Zhang F, Wu H, et al. Wilms' tumor 1 (WT1) expression and prognosis in solid cancer patients: a systematic review and meta-analysis[J]. Sci Rep, 2015(05):8924.

Park S Y, Roh S J, Kim Y N, et al. Expression of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: prognostic impact[J]. Oncol Rep, 2009(03):649-657.

Kaida M, Morita-Hoshi Y, Soeda A, et al. Phase 1 trial of Wilms tumor 1 (WT1) peptide vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary tract cancer[J]. J Immunother, 2011(01):92-99.

Yamamoto K, Ueno T, Kawaoka T, et al. MUC1 peptide vaccination in patients with advanced pancreas or biliary tract cancer[J]. Anticancer Res, 2005(05):3575-3579.

Koido S, Kan S, Yoshida K, et al. Immunogenic modulation of cholangiocarcinoma cells by chemoimmunotherapy[J]. Anticancer Res, 2014(11):6353-6361.

Aruga A, Takeshita N, Kotera Y, et al. Long-term Vaccination with Multiple Peptides Derived from Cancer-Testis Antigens Can Maintain a Specific T-cell Response and Achieve Disease Stability in Advanced Biliary Tract Cancer[J]. Clin Cancer Res, 2013(08):2224-2231.

Aruga A, Takeshita N, Kotera Y, et al. Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer[J]. J Transl Med, 2014(12):61.

Yoshitomi M, Yutani S, Matsueda S, et al. Personalized peptide vaccination for advanced biliary tract cancer: IL-6, nutritional status and pre-existing antigen-specific immunity as possible biomarkers for patient prognosis[J]. Exp Ther Med, 2012(03):463-469.

Kobayashi M, Sakabe T, Abe H, et al. Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer[J]. J Gastrointest Surg, 2013(09):1609-17.

Lepisto A J, Moser A J, Zeh H, et al. A phase I/II study of a MUC1 peptide pulsed autologous dendritic cell vaccine as adjuvant therapy in patients with resected pancreatic and biliary tumors[J]. Cancer Ther, 20086(B): 955-964.

Lokman N A, Ween M P, Oehler M K, et al. The role of annexin A2 in tumorigenesis and cancer progression[J]. Cancer Microenviron, 2011(02):199-208.

Yonglitthipagon P, Pairojkul C, Chamgramol Y, et al. Up-regulation of annexin A2 in cholangiocarcinoma caused by Opisthorchis viverrini and its implication as a prognostic marker[J]. Int J Parasitol, 2010(10):1203-12.

Rucki A A, Foley K, Zhang P, et al. Heterogeneous Stromal Signaling within the Tumor Microenvironment Controls the Metastasis of Pancreatic Cancer[J]. Cancer Res, 2017(01):41-52.

Rosenberg S A, Restifo N P, Yang J C, et al. Adoptive cell transfer: a clinical path to effective cancer immunotherapy[J]. Nat Rev Cancer, 2008(04):299-308.

Dudley M E, Gross C A, Langhan M M, et al. CD8+ enriched "young" tumor infiltrating lymphocytes can mediate regression of metastatic melanoma[J]. Clin Cancer Res, 2010(24)6122-31.

Higuchi R, Yamamoto M, Hatori T, et al. Intrahepatic cholangiocarcinoma with lymph node metastasis successfully treated by immunotherapy with CD3-activated T cells and dendritic cells after surgery: report of a case[J]. Surg Today, 2006(06):559-62.

Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer[J]. Science, 2014(6184): 641-645.

Shimizu K, Kotera Y, Aruga A, et al. Clinical utilization of postoperative dendritic cell vaccine plus activated T-cell transfer in patients with intrahepatic cholangiocarcinoma[J]. J Hepatobiliary Pancreat Sci, 2012(02):171-8.

买新佳,黄婧娟,陈洪雷.新兴免疫检查点VISTA在肿瘤与炎症中的作用[J].武汉大学学报(医学版),2020(02):275-279.

DOI: http://dx.doi.org/10.26549/yzlcyxzz.v3i6.5835