TSA-DC-CTL 细胞免疫治疗联合 PD-L1 抗体治疗高龄晚期结肠癌 1 例报道并文献复习_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

胡时栋 ¹ , 李松岩 ¹ , 晏阳 ¹ , 滕达 ¹ , 柳辛墨 ¹ , 何长征 ¹ , 邢晓伟 ¹ , 李宇轩 ¹ , 王玉锋 ² ,  杜晓辉 ¹

1. ;
2. ;

Corresponding author：

杜晓辉, Email: duxiaohui301pw@163.com

Keywords：

细胞免疫治疗; 程序性死亡配体 1; 晚期结肠癌

DOI：

10.7507/1007-9424.201901002

Video：

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目的报道 1 例肿瘤特异性抗原（TSA）刺激诱导树突状细胞（DC）及细胞毒性 T 淋巴细胞（CTL）过继治疗联合程序性死亡配体 1（PD-L1）抗体治疗高龄晚期结肠癌患者。方法 2018 年 2 月笔者所在医院对 1 例 90 岁高龄女性患者因“回盲部癌伴梗阻”行剖腹探查、回盲部切除、小肠部分切除、末端回肠造瘘、腹膜活检术，肿瘤广泛转移，患者基础条件差，术后无法耐受常规治疗。经与患者家属充分沟通知情同意及解放军总医院伦理委员会批准，于术后 4 个月开始行 4 次 TSA-DC 细胞皮内多点注射，4 次 TSA-CTL 细胞静脉滴注，2 次 TSA-CTL 细胞腹腔注入，1 次 PD-L1 抗体 1 200 mg 静脉滴注。结果行 TSA-DC-CTL 联合 PD-L1 治疗后 7 d（治疗中期），患者的 KPS 评分升至 80 分（治疗前 40 分），外周血循环肿瘤细胞计数降至 7 个/3.2 mL（治疗前 16 个/3.2 mL），肿瘤标志物 CA125 降至 155.5 u/mL（治疗前 224.4 u/mL），治疗过程中未见相关不良反应。行 TSA-DC-CTL 联合 PD-L1 治疗后 36 d 患者突然出现血压和血氧饱和度下降，给与升压、兴奋呼吸等治疗，情况好转，因家属要求患者自动出院。结论 TSA-DC-CTL 细胞免疫治疗联合 PD-L1 治疗本例高龄患者安全可行，能在一定程度上改善患者生活质量及部分生物学指标，但 TSA-DC-CTL 联合 PD-L1 抗体的安全性及近远期疗效有待进一步研究论证。

Citation： 胡时栋, 李松岩, 晏阳, 滕达, 柳辛墨, 何长征, 邢晓伟, 李宇轩, 王玉锋, 杜晓辉. TSA-DC-CTL 细胞免疫治疗联合 PD-L1 抗体治疗高龄晚期结肠癌 1 例报道并文献复习. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(6): 739-741. doi: 10.7507/1007-9424.201901002 Copy

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12.	钱其军, 吴孟超. 肿瘤精准细胞免疫治疗: 梦想照进现实. 中国肿瘤生物治疗杂志, 2015, 22(2): 151-158.
13.	Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008, 26: 677-704.
14.	Chakravarti N, Prieto VG. Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis. Transl Lung Cancer Res, 2015, 4(6): 743-751.
15.	Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med, 2012, 209(6): 1201-1217.
16.	Motzer RJ, Escudier B, Mcdermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med, 2015, 373(19): 1803-1813.
17.	Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet, 2017, 390(10105): 1853-1862.
18.	Ramos-Esquivel A, van der Laat A, Rojas-Vigott R, et al. Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised clinical trials. ESMO Open, 2017, 2(3): e000236.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Kemeny NE. Treatment of metastatic colon cancer: "the times they are A-changing". J Clin Oncol, 2013, 31(16): 1913-1916.
3. 王广伟, 顾元龙, 胡森焱. 人热休克蛋白 70-肽复合物/树突状细胞对肝癌的免疫治疗效果研究. 中国普外基础与临床杂志, 2017, 24(2): 222-227.
4. 邹一丰, 吴小剑, 兰平. 结直肠癌免疫治疗. 中国普外基础与临床杂志, 2006, 13(3): 358-361.
5. Gopal S. Moonshot to Malawi. N Engl J Med, 2016, 374(17): 1604-1605.
6. Cohen RL, Settleman J. From cancer genomics to precision oncology—tissue's still an issue. Cell, 2014, 157(7): 1509-1514.
7. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science, 2013, 342(6165): 1432-1433.
8. de Kock I, Mirhosseini M, Lau F, et al. Conversion of Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG) to Palliative Performance Scale (PPS), and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care, 2013, 29(3): 163-169.
9. Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science, 2015, 348(6230): 62-68.
10. Robbins PF, Lu YC, El-Gamil M, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med, 2013, 19(6): 747-752.
11. Tran E, Turcotte S, Gros A, et al. Cancer immunotherapy based on mutation-specific CD4⁺ T cells in a patient with epithelial cancer. Science, 2014, 344(6184): 641-645.
12. 钱其军, 吴孟超. 肿瘤精准细胞免疫治疗: 梦想照进现实. 中国肿瘤生物治疗杂志, 2015, 22(2): 151-158.
13. Keir ME, Butte MJ, Freeman GJ, et al. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol, 2008, 26: 677-704.
14. Chakravarti N, Prieto VG. Predictive factors of activity of anti-programmed death-1/programmed death ligand-1 drugs: immunohistochemistry analysis. Transl Lung Cancer Res, 2015, 4(6): 743-751.
15. Yokosuka T, Takamatsu M, Kobayashi-Imanishi W, et al. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med, 2012, 209(6): 1201-1217.
16. Motzer RJ, Escudier B, Mcdermott DF, et al. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med, 2015, 373(19): 1803-1813.
17. Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced melanoma: final overall survival results of a multicentre, randomised, open-label phase 3 study (KEYNOTE-006). Lancet, 2017, 390(10105): 1853-1862.
18. Ramos-Esquivel A, van der Laat A, Rojas-Vigott R, et al. Anti-PD-1/anti-PD-L1 immunotherapy versus docetaxel for previously treated advanced non-small cell lung cancer: a systematic review and meta-analysis of randomised clinical trials. ESMO Open, 2017, 2(3): e000236.

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

TSA-DC-CTL 细胞免疫治疗联合 PD-L1 抗体治疗高龄晚期结肠癌 1 例报道并文献复习

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