TSA-DC-CTL 細胞免疫治療聯合 PD-L1 抗體治療高齡晚期結腸癌 1 例報道并文獻復習_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

胡時棟 ¹ , 李松巖 ¹ , 晏陽 ¹ , 滕達 ¹ , 柳辛墨 ¹ , 何長征 ¹ , 邢曉偉 ¹ , 李宇軒 ¹ , 王玉鋒 ² ,  杜曉輝 ¹

1. ;
2. ;

Corresponding?author：

杜曉輝, Email: duxiaohui301pw@163.com

Keywords：

細胞免疫治療; 程序性死亡配體 1; 晚期結腸癌

DOI：

10.7507/1007-9424.201901002

Video：

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目的報道 1 例腫瘤特異性抗原（TSA）刺激誘導樹突狀細胞（DC）及細胞毒性 T 淋巴細胞（CTL）過繼治療聯合程序性死亡配體 1（PD-L1）抗體治療高齡晚期結腸癌患者。方法 2018 年 2 月筆者所在醫院對 1 例 90 歲高齡女性患者因“回盲部癌伴梗阻”行剖腹探查、回盲部切除、小腸部分切除、末端回腸造瘺、腹膜活檢術，腫瘤廣泛轉移，患者基礎條件差，術后無法耐受常規治療。經與患者家屬充分溝通知情同意及解放軍總醫院倫理委員會批準，于術后 4 個月開始行 4 次 TSA-DC 細胞皮內多點注射，4 次 TSA-CTL 細胞靜脈滴注，2 次 TSA-CTL 細胞腹腔注入，1 次 PD-L1 抗體 1 200 mg 靜脈滴注。結果行 TSA-DC-CTL 聯合 PD-L1 治療后 7 d（治療中期），患者的 KPS 評分升至 80 分（治療前 40 分），外周血循環腫瘤細胞計數降至 7 個/3.2 mL（治療前 16 個/3.2 mL），腫瘤標志物 CA125 降至 155.5 u/mL（治療前 224.4 u/mL），治療過程中未見相關不良反應。行 TSA-DC-CTL 聯合 PD-L1 治療后 36 d 患者突然出現血壓和血氧飽和度下降，給與升壓、興奮呼吸等治療，情況好轉，因家屬要求患者自動出院。結論 TSA-DC-CTL 細胞免疫治療聯合 PD-L1 治療本例高齡患者安全可行，能在一定程度上改善患者生活質量及部分生物學指標，但 TSA-DC-CTL 聯合 PD-L1 抗體的安全性及近遠期療效有待進一步研究論證。

Citation： 胡時棟, 李松巖, 晏陽, 滕達, 柳辛墨, 何長征, 邢曉偉, 李宇軒, 王玉鋒, 杜曉輝. TSA-DC-CTL 細胞免疫治療聯合 PD-L1 抗體治療高齡晚期結腸癌 1 例報道并文獻復習. 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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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.	錢其軍, 吳孟超. 腫瘤精準細胞免疫治療: 夢想照進現實. 中國腫瘤生物治療雜志, 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. 王廣偉, 顧元龍, 胡森焱. 人熱休克蛋白 70-肽復合物/樹突狀細胞對肝癌的免疫治療效果研究. 中國普外基礎與臨床雜志, 2017, 24(2): 222-227.
4. 鄒一豐, 吳小劍, 蘭平. 結直腸癌免疫治療. 中國普外基礎與臨床雜志, 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. 錢其軍, 吳孟超. 腫瘤精準細胞免疫治療: 夢想照進現實. 中國腫瘤生物治療雜志, 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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TSA-DC-CTL 細胞免疫治療聯合 PD-L1 抗體治療高齡晚期結腸癌 1 例報道并文獻復習

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