胰腺癌肝转移免疫治疗的研究进展

金添强; 徐锋; 戴朝六

doi:10.3969/j.issn.1001-5256.2018.11.044

胰腺癌肝转移免疫治疗的研究进展

DOI: 10.3969/j.issn.1001-5256.2018.11.044

中国医科大学附属盛京医院肝胆脾外科

基金项目:

沈阳市科学技术计划项目(17-230-9-16)；

详细信息

中图分类号: R735.9
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- 被引次数: 0
出版历程
- 出版日期: 2018-11-20

Research advances in immunotherapy for liver metastasis of pancreatic cancer

Research funding:

摘要

摘要: 胰腺癌肝转移的预后极差,手术切除机会少,传统放化疗对其疗效也不理想。免疫治疗作为新的肿瘤治疗策略,能够通过增强患者免疫功能以对抗肿瘤,有望成为胰腺癌肝转移的有效治疗方案。针对免疫调节剂、单克隆抗体、免疫检查点抑制剂、过继细胞免疫和肿瘤疫苗方面,总结了近年来免疫疗法在胰腺癌肝转移治疗中的研究进展,认为联合治疗方案具有积极的应用前景。
- 胰腺肿瘤 /
- 肝肿瘤 /
- 肿瘤转移 /
- 免疫疗法 /
- 综述
Abstract: Patients with liver metastasis of pancreatic cancer have poor prognosis and few opportunities for surgery, and conventional radiochemotherapy lacks a satisfactory effect. As a new therapeutic strategy for tumor, immunotherapy fights against cancer by enhancing patients' immune function and may thus become an effective treatment regimen for liver metastasis of pancreatic cancer. This article reviews the latest research advances in immunotherapy for liver metastasis of pancreatic cancer from the aspects of immunomodulator, monoclonal antibody, immune checkpoint inhibitor, adoptive cellular immunotherapy, and tumor vaccine and points out that a combined treatment regimen has a promising future in clinical application.
- pancreatic neoplasms /
- liver neoplasms /
- neoplasm metastasis /
- immunotherapy /
- review

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参考文献(48)

[1] CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66 (2) :115-132.

[2] LIU X, GUO XZ. Early diagnosis of pancreatic cancer[J]. J Clin Hepatol, 2016, 32 (5) :864-866. (in Chinese) 刘旭, 郭晓钟.胰腺癌的早期诊断[J].临床肝胆病杂志, 2016, 32 (5) :864-866.

[3] ZHU LN, LIN F, SHANG ZN, et al. Mechanism of action of recombinant interleukin-2 combined with allicin in treatment of pancreatic cancer[J]. J Clin Hepatol, 2016, 32 (10) :1943-1946. (in Chinese) 朱立宁, 林峰, 商振宁, 等.重组IL-2联合大蒜素治疗胰腺癌的作用机制[J].临床肝胆病杂志, 2016, 32 (10) :1943-1946.

[4] MATSUMOTO G, NAGAI S, MUTA M, et al. Survival benefit of KRN7000 immune therapy in combination with TNP470 in hamster liver metastasis model of pancreatic cancer[J]. Oncol Rep, 2003, 10 (5) :1201-1206.

[5] WOLPIN BM, O'REILLY EM, KO YJ, et al. Global, multicenter, randomized, phase II trial of gemcitabine and gemcitabine plus AGS-1C4D4 in patients with previously untreated, metastatic pancreatic cancer[J]. Ann Oncol, 2013, 24 (7) :1792-1801.

[6] VONDERHEIDE R, BAJOR D, WINOGRAD R, et al. CD40 immunotherapy for pancreatic cancer[J]. Cancer Immunol Immunother, 2013, 62 (5) :949-954.

[7] BEATTY GL, CHIOREAN EG, FISHMAN MP, et al. CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans[J]. Science, 2011, 331 (6024) :1612-1616.

[8] XU BB, HE YJ, WANG WL, et al. Research progress of immune checkpoint therapy for cancer[J]. Chin J Clin Pharmacol Ther, 2016, 21 (2) :218-224. (in Chinese) 许标波, 贺毅憬, 王韦力, 等.肿瘤免疫检查点抑制剂临床治疗的研究进展[J].中国临床药理学与治疗学, 2016, 21 (2) :218-224.

[9] ROYAL R, 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.

[10] LE D, LUTZ E, URAM J, et al. Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer[J]. J Immunother, 2013, 36 (7) :382-389.

[11] AGLIETTA M, BARONE C, SAWYER MB, et al. A phase I dose escalation trial of tremelimumab (CP-675, 206) in combination with gemcitabine in chemotherapy-naive patients with metastatic pancreatic cancer[J]. Ann Oncol, 2014, 25 (9) :1750-1755.

[12] BRAHMER JR, TYKODI SS, CHOW LQM, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer[J]. N Engl J Med, 2012, 366 (26) :2455-2465.

[13] SOARES K, RUCKI A, WU A, et al. PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors[J]. J Immunother, 2015, 38 (1) :1-11.

[14] WINOGRAD R, BYRNE KT, EVANS RA, et al. Induction of T-cell immunity overcomes complete resistance to PD-1 and CTLA-4 blockade and improves survival in pancreatic carcinoma[J]. Cancer Immunol Res, 2015, 3 (4) :399-411.

[15] VONDERHEIDE RH. CD47 blockade as another immune checkpoint therapy for cancer[J]. Nat Med, 2015, 21 (10) :1122.

[16] MICHAELS AD, NEWHOOK TE, ADAIR SJ, et al. CD47 blockade as an adjuvant immunotherapy for resectable pancreatic cancer[J]. Clin Cancer Res, 2018, 24 (6) :1415-1425.

[17] GOLUBOVSKAYA V, BERAHOVICH R, ZHOU H, et al. CD47-CAR-T cells effectively kill target cancer cells and block pancreatic tumor growth[J]. Cancers, 2017, 9 (10) :139.

[18] IBRAHIM AM, WANG YH. Viro-immune therapy:A new strategy for treatment of pancreatic cancer[J]. World J Gastroenterol, 2016, 22 (2) :748-763.

[19] WANG M, SHI SB, QI JL, et al. S-1 plus CIK as second-line treatment for advanced pancreatic cancer[J]. Med Oncol, 2013, 30 (4) :747.

[20] CHUNG M, PARK J, BANG S, et al. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer[J]. Cancer Immunol Immunother, 2014, 63 (9) :939-946.

[21] JIANG N, QIAO G, WANG X, et al. Dendritic cell/cytokine-induced killer cell immunotherapy combined with S-1 in patients with advanced pancreatic cancer:A prospective study[J]. Clin Cancer Res, 2017, 23 (17) :5066-5073.

[22] LIU AF, XIN LY, ZHONG SS, et al. Research progress on chimeric antigen receptor T-cell in hematological malignacies[J]. Chin J Cancer Prev Treat, 2016, 23 (19) :1333-1338. (in Chinese) 刘爱飞, 辛柳燕, 钟思思, 等.嵌合抗原受体型T淋巴细胞在血液肿瘤中的研究进展[J].中华肿瘤防治杂志, 2016, 23 (19) :1333-1338.

[23] DESELM CJ, TANO ZE, VARGHESE AM, et al. CAR T-cell therapy for pancreatic cancer[J]. J Surg Oncol, 2017, 116 (1) :63-74.

[24] CHMIELEWSKI M, HAHN O, RAPPL G, et al. T cells that target carcinoembryonic antigen eradicate orthotopic pancreatic carcinomas without inducing autoimmune colitis in mice[J]. Gastroenterology, 2012, 143 (4) :1095-1107.

[25] JIANG H, SONG B, WANG P, et al. Efficient growth suppression in pancreatic cancer PDX model by fully human anti-mesothelin CAR-T cells[J]. Protein Cell, 2017, 8 (12) :926-931.

[26] BEATTY GL, O'HARA MH, LACEY SF, et al. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial[J]. Gastroenterology, 2018, 155 (1) :29-32.

[27] MOHAMMED S, SUKUMARAN S, BAJGAIN P, et al. Improving chimeric antigen receptor-modified T cell function by reversing the immunosuppressive tumor microenvironment of pancreatic cancer[J]. Mol Ther, 2017, 25 (1) :249-258.

[28] BATCHU RB, GRUZDYN OV, MAHMUD EM, et al. Inhibition of interleukin-10 in the tumor microenvironment can restore mesothelin chimeric antigen receptor T cell activity in pancreatic cancer in vitro[J]. Surgery, 2018, 163 (3) :627-632.

[29] MASUYAMA J, MURAKAMI T, IWAMOTO S, et al. Ex vivo expansion of natural killer cells from human peripheral blood mononuclear cells co-stimulated with anti-CD3 and anti-CD52 monoclonal antibodies[J]. Cytotherapy, 2016, 18 (1) :80-90.

[30] LIN M, ALNAGGAR M, LIANG S, et al. An important discovery on combination of irreversible electroporation and allogeneic natural killer cell immunotherapy for unresectable pancreatic cancer[J].Oncotarget, 2017, 8 (60) :101795-101807.

[31] LIN M, LIANG S, WANG X, et al. Percutaneous irreversible electroporation combined with allogeneic natural killer cell immunotherapy for patients with unresectable (stage III/IV) pancreatic cancer:A promising treatment[J]. J Cancer Res Clin Oncol, 2017, 143 (12) :2607-2618.

[32] COVELER A, ROSSI G, VAHANIAN N, et al. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma[J]. Immunotherapy, 2016, 8 (2) :117-125.

[33] HARDACRE JM, MULCAHY M, SMALL W, et al. Addition of algenpantucel-L immunotherapy to standard adjuvant therapy for pancreatic cancer:A phase 2 study[J]. J Gastrointest Surg, 2013, 17 (1) :94-100.

[34] LUTZ E, YEO CJ, LILLEMOE KD, et al. A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation[J]. Ann Surg, 2011, 253 (2) :328-335.

[35] LAHERU D, LUTZ E, BURKE J, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer:A pilot study of safety, feasibility, and immune activation[J]. Clin Cancer Res, 2008, 14 (5) :1455-1463.

[36] GJERTSEN MK, BUANES T, ROSSELAND AR, et al. Intradermal ras peptide vaccination with granulocyte-macrophage colonystimulating factor as adjuvant:Clinical and immunological responses in patients with pancreatic adenocarcinoma[J]. Int J Cancer, 2001, 92 (3) :441-450.

[37] ABOU-ALFA GK, CHAPMAN PB, FEILCHENFELDT J, et al. Targeting mutated K-ras in pancreatic adenocarcinoma using an adjuvant vaccine[J]. Am J Clin Oncol, 2011, 34 (3) :321-325.

[38] VAKOC CR, TUVESON DA. Untangling the genetics from the epigenetics in pancreatic cancer metastasis[J]. Nat Genet, 2017, 49 (3) :323-324.

[39] BERNHARDT SL, GJERTSEN MK, TRACHSEL S, et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer:A dose escalating phase I/II study[J]. Br J Cancer, 2006, 95 (11) :1474-1482.

[40] STAFF C, MOZAFFARI F, FRODIN JE, et al. Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients[J]. Int J Oncol, 2014, 45 (3) :1293-1303.

[41] MIDDLETON G, SILCOCKS P, COX T, et al. Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac) :An open-label, randomised, phase 3 trial[J]. Lancet Oncol, 2014, 15 (8) :829-840.

[42] SHANG N, FIGINI M, SHANGGUAN J, et al. Dendritic cells based immunotherapy[J]. Am J Cancer Res, 2017, 7 (10) :2091-2102.

[43] GHANSAH T, VOHRA N, KINNEY K, et al. Dendritic cell immunotherapy combined with gemcitabine chemotherapy enhances survival in a murine model of pancreatic carcinoma[J]. Cancer Immunol Immunother, 2013, 62 (6) :1083-1091.

[44] SHINDO Y, HAZAMA S, MAEDA Y, et al. Adoptive immunotherapy with MUC1-m RNA transfected dendritic cells and cytotoxic lymphocytes plus gemcitabine for unresectable pancreatic cancer[J]. J Transl Med, 2014, 12:175.

[45] COSTA NEVES M, GIAKOUSTIDIS A, STAMP G, et al. Extended survival after complete pathological response in metastatic pancreatic ductal adenocarcinoma following induction chemotherapy, chemoradiotherapy, and a novel immunotherapy agent, IMM-101[J].Cureus, 2015, 7 (12) :e435.

[46] DALGLEISH AG. Long term survival in IMAGE 1 (immune modulation and gemcitabine evaluation 1) , a randomized, open-label phase II trial comparing gemcitabine with and without IMM-101 in advanced pancreatic cancer[J]. J Clin Oncol, 2015, 33 (Suppl15) :3051.

[47] LE DT, BROCKSTEDT DG, NIR-PAZ R, et al. A live-attenuated Listeria vaccine (ANZ-100) and a live-attenuated Listeria vaccine expressing mesothelin (CRS-207) for advanced cancers:Phase I studies of safety and immune induction[J]. Clin Cancer Res, 2012, 18 (3) :858-868.

[48] LE DT, WANG-GILLAM A, PICOZZI V, et al. Safety and survival with GVAX pancreas prime and listeria monocytogenes-expressing mesothelin (CRS-207) boost vaccines for metastatic pancreatic cancer[J]. J Clin Oncol, 2015, 33 (12) :1325-1333.

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