切换至 "中华医学电子期刊资源库"

中华细胞与干细胞杂志(电子版) ›› 2017, Vol. 07 ›› Issue (01) : 54 -58. doi: 10.3877/cma.j.issn.2095-1221.2017.01.010

所属专题: 文献

综述

γδT细胞及其在肿瘤免疫治疗中的研究进展
肖凌1, 张钦1, 陈虎1, 张斌1,()   
  1. 1. 100071 北京,解放军307医院造血干细胞移植科 全军造血干细胞研究所
  • 收稿日期:2016-05-18 出版日期:2017-02-01
  • 通信作者: 张斌
  • 基金资助:
    北京市科技计划课题(Z161100000516184)

Development of gammadelta T cells in tumor immunotherapy

Ling Xiao1, Qin Zhang1, Hu Chen1, Bin Zhang1,()   

  1. 1. Department of Hematopoietic Stem Cell Transplantation, the 307th Hospital of Chinese People's Liberation Army, Beijing 100071, China
  • Received:2016-05-18 Published:2017-02-01
  • Corresponding author: Bin Zhang
  • About author:
    Corresponding author: Zhang Bin, Email:
引用本文:

肖凌, 张钦, 陈虎, 张斌. γδT细胞及其在肿瘤免疫治疗中的研究进展[J/OL]. 中华细胞与干细胞杂志(电子版), 2017, 07(01): 54-58.

Ling Xiao, Qin Zhang, Hu Chen, Bin Zhang. Development of gammadelta T cells in tumor immunotherapy[J/OL]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2017, 07(01): 54-58.

γδT细胞是T细胞的一个亚群,其TCR由γ链和δ链组成,为主要组织相容性复合体非限制性细胞。外周血γδT细胞大部分表达TCR Vγ9和Vδ2,能杀伤多种肿瘤细胞。本文将对γδT细胞的免疫学特性包括识别杀伤肿瘤细胞的机制及γδT细胞在肿瘤免疫治疗中的研究作一综述。

Gammadelta T cells are a small subset of T lymphocytes expressingγ-andδ-chain T cell receptors. Gammadelta T cells are main MHC-unrestrictive cells. The majority of human peripheral blood Gammadelta T cells express Vγ9 and Vδ2 T cell receptor and show cytotoxicity against a wide spectrum of tumor cells. Here, we review the immunological properties of gammadelta T cells including the recognition and killing mechanism against tumor cells, and summarize the results of gammadelta T cell-based cancer immunotherapy.

图1 γδT细胞的激活
表1 应用γδT细胞过继输注的临床试验
表2 应用Zoledronate和IL-2体内扩增γδT细胞的治疗方案
1
Brenner MB, Mclean J, Dialynas DP, et al. Identification of a putative second T-cell receptor[J].Nature, 1986, 322(675):145-149.
2
Van Acker HH, Anguille S, Van Tendeloo VF, et al. Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy[J]. Oncoimmunology, 2015, 4(8):e1021538.
3
Legut M, Cole DK, Sewell AK. The promise of gamma delta T cells and the gamma delta T cell receptor for cancer immunotherapy[J]. Cell Mol Immunol, 2015, 12(6):656-668.
4
Toia F, Buccheri S, Anfosso A, et al. Skewed differentiation of circulating V gamma 9V delta 2 T lymphocytes in melanoma and impact on clinical outcome[J]. PLoS One, 2016, 11(2):e0149570.
5
Fowler DW, Bodman-Smith MD. Harnessing the power of Vδ2 cells in cancer immunotherapy[J]. Clin Exp Immunol, 2015, 180(1):1-10.
6
Sugai S, Yoshikawa T, Iwama T, et al. Hepatocellular carcinoma cell sensitivity to V gamma 9V delta 2 T lym-phocyte-mediated killing is increased by zoledronate[J]. Int J Oncol, 2016, 48(5):1794-1804.
7
Silva SB, Serre K, Norell H.γδT cells in cancer[J]. Nat Rev Immunol, 2015, 15(11):683-691.
8
Harly C, PeignéCM, Scotet E. Molecules and mechanisms implicated in the peculiar antigenic activation process of human Vγ9Vδ2 T Cells[J]. Front Immunol, 2015, 5:657.
9
Decaup E, Duault C, Bezombes C, et al. Phosphoantigens and butyrophilin 3A1 induce similar intracellular activation signaling in human TCRV gamma 9(+) gamma delta T lymphocytes[J]. Immunol Lett, 2014, 161(1):133-137.
10
Lanier LL. NKG2D receptor and its ligands in host defense[J]. Cancer Immunol Res, 2015, 3(6):575-582.
11
Van Acker HH, Anguille S, Willemen Y, et al. Bisphosphonates for cancer treatment: Mechanisms of action and lessons from clinical trials[J]. Pharmacol Ther, 2016, 158:24-40.
12
Tyler CJ, Doherty DG, Moser BA. Human V gamma 9/V delta 2 T cells: innate adaptors of the immune system[J]. Cell Immunol, 2015, 296(1):10-21.
13
Paul S, Lal G. Regulatory and effector functions of gamma-delta (gammadelta) T cells and their therapeutic potential in adoptive cellular therapy for cancer[J]. Int J Cancer, 2016, 139(5):976-985.
14
Li K, Zhang Q, Zhang Y, et al. T-cell-associated cellular immunotherapy for lung cancer[J]. J Cancer Res Clin Oncol, 2015, 141(7):1249-1258.
15
Wilhelm M, Smetak M, Schaefer-Eckart K, et al. Successful adoptive transfer and invi-voexpansion of haploidenticalγδT cells[J]. J Transl Med, 2014, 12:45.
16
Wada I, Matsushita H, Noji S, et al. Intraperitoneal injection ofin vitroexpanded V gamma 9V delta 2 T cells together with zoledronate for the treatment of malignant ascites due to gastric cancer[J]. Cancer Med, 2014, 3(2):362-375.
17
Khan MW, Eberl M, Moser B. Potential use ofγδT cell-based vaccines in cancer immunotherapy[J]. Front Immunol, 2014, 5:512.
18
Bennouna J, Bompas E, Neidhardt EM, et al. Phase-i study of innacell gammadelta,an autologous cell-therapy product highly enriched in gamma9delta2 T lymphocytes,in combination with il-2, in patients with metastatic renal cell carcinoma[J]. Cancer Immunol Immunother, 2008, 57(11):1599-1609.
19
Kobayashi H, Tanaka Y, Shimmura HA, et al. Complete remission of lung metastasis following adoptive im-munotherapy using activated autologous gamma delta T-cells in a patient with renal cell carcinoma[J]. Anticancer Res, 2010, 30(2):575-579.
20
Nakajima J, Murakawa T, Fukami T, et al. A phase I study of adoptive immunotherapy for recurrent non-small-cell lung cancer patients with autologous gamma delta T cells[J]. Eur J Cardiothorac Surg, 2010, 37(5):1191-1197.
21
Izumi T, Kondo M, Takahashi T, et al.Ex vivocharacterization of gamma delta T-cell repertoire in patients after adoptive transfer of V gamma 9V delta 2 T cells expressing the interleukin-2 receptor beta-chain and the common gamma-chain[J]. Cytotherapy, 2013, 15(4):481-491.
22
Abe Y, Muto M, Nieda M, et al. Clinical and immunological evaluation of zoledronate-activated V gamma 9 gamma delta T-cell-based immunotherapy for patients with multiple myeloma[J]. Exp Hematol, 2009, 37(8):956-968.
23
Meraviglia S, Eberl M, Vermijlen D, et al.In vivomanipulation of V gamma 9V delta 2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients[J]. Clin Exp Immunol, 2010, 161(2):290-297.
24
Kobayashi H, Tanaka Y, Yagi J, et al. Phase I/II study of adoptive transfer ofγδT cells in combination with zoledronic acid and IL-2 to patientswith advanced renal cell carcinoma[J]. Cancer Immunol Immunother, 2011, 60(8):1075-84.
25
Sakamoto M, Nakajima J, Murakawa T, et al. Adop-tive immunotherapy for advanced non-small cell lung cancer using zoledronate-expandedγδTcells: aphase I clinical study[J]. J Immunother, 2011, 34(2):202-211.
26
Abe Y, Muto M, Nieda M, et al. Clinical and immunological evaluation of zoledronate-activated Vgamma9gammadelta T-cell-based immunotherapy for patients with multiple myeloma[J]. Exp Hematol, 2009, 37(8):956-968.
27
Nicol AJ, Tokuyama H, Mattarollo SR, et al. Clinical evaluation of autologous gamma delta T cell-based im-munotherapy for metastatic solid tumours[J]. Br J Cancer, 2011, 105(6):778-786.
28
Kunzmann V, Smetak M, Kimmel B, et al. Tumor-promoting versus tumor-antagonizing roles ofγδT cells in cancer immunotherapy: results from aprospective phase I/II trial[J]. J Immunother, 2012, 35(2):205-213.
29
Lang JM, Kaikobad MR, Wallace M, et al. Pi-lot trial of interleukin-2 and zoledronic acid to augmentγδT cells as treatment for patients with refractoryrenal cell carcinoma[J]. Cancer Immunol Immunother, 2011, 60(10):1447-1460.
30
Kobayashi H, Tanaka Y.γδT cell Immunotherapy-A review[J]. Pharmaceuticals(Basel), 2015, 8(1):40-61.
31
Coffelt SB, Kersten K, Doornebal CW, et al. IL-17-producingγδT cells and neutrophils conspire to promote breast cancer metastasis[J]. Nature, 2015, 522(7556):345-348.
32
Zhong FY, Cui DW, Tao H, et al. IL-17A-producing T cells and associated cytokines are involved in the pro-gression of gastric cancer[J].Oncol Rep, 2015, 34(5):2365-2374.
33
Ribot JC, Ribeiro ST, Correia DV, et al. Hu-manγδthymocytes are functionally immature and differentiate into cytotoxic type 1 effector T cells uponIL-2/IL-15 signaling[J]. J Immunol, 2014, 192(5):2237-2243.
34
Deng X, Terunuma H, Terunuma A, et al.Ex vivo-expanded natural killer cells kill cancer cells more effectively than ex vivo-expandedγδ t cells or αβt cells[J]. Int Immunopharmacol, 2014, 22(2):486-491.
35
Niu C, Jin HF, Li M, et al.In vitroanalysis of the proliferative capacity and cytotoxic effects ofex vivoinduced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells[J]. BMC Immunol, 2015, 16:61.
36
Oberg HH, Peipp M, Kellner C, et al. Nov-el bispecific antibodies increaseγδT-cell cytotoxicity against pancreatic cancer cells[J]. Cancer Res, 2014, 74(5):1349-1360.
37
Oberg HH, Kellner C, Gonnermann D, et al.γδT cell activation by bispecific antibodies[J].Cellular Immunol, 2015, 2961(1):41-49.
[1] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[2] 李国新, 陈新华. 全腹腔镜下全胃切除术食管空肠吻合的临床研究进展[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 1-4.
[3] 陈方鹏, 杨大伟, 金从稳. 腹腔镜近端胃癌切除术联合改良食管胃吻合术重建His角对术后反流性食管炎的效果研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 15-18.
[4] 许杰, 李亚俊, 韩军伟. 两种入路下腹腔镜根治性全胃切除术治疗超重胃癌的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 19-22.
[5] 李刘庆, 陈小翔, 吕成余. 全腹腔镜与腹腔镜辅助远端胃癌根治术治疗进展期胃癌的近中期随访比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 23-26.
[6] 刘世君, 马杰, 师鲁静. 胃癌完整系膜切除术+标准D2根治术治疗进展期胃癌的近中期随访研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 27-30.
[7] 任佳, 马胜辉, 王馨, 石秀霞, 蔡淑云. 腹腔镜全胃切除、间置空肠代胃术的临床观察[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 31-34.
[8] 赵丽霞, 王春霞, 陈一锋, 胡东平, 张维胜, 王涛, 张洪来. 内脏型肥胖对腹腔镜直肠癌根治术后早期并发症的影响[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 35-39.
[9] 吴晖, 佴永军, 施雪松, 魏晓为. 两种解剖入路下行直肠癌侧方淋巴结清扫的效果比较[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 40-43.
[10] 周世振, 朱兴亚, 袁庆港, 刘理想, 王凯, 缪骥, 丁超, 汪灏, 管文贤. 吲哚菁绿荧光成像技术在腹腔镜直肠癌侧方淋巴结清扫中的应用效果分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 44-47.
[11] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[12] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[13] 徐逸男. 不同术式治疗梗阻性左半结直肠癌的疗效观察[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 72-75.
[14] 王露, 周丽君. 全腹腔镜下远端胃大部切除不同吻合方式对胃癌患者胃功能恢复、并发症发生率的影响[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 92-95.
[15] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
阅读次数
全文


摘要