-
摘要:
目前免疫治疗正在非小细胞肺癌、黑色素瘤、膀胱癌等各个瘤种中如火如荼地开展，其治疗方法也多种多样，包括肿瘤疫苗治疗、过继性T细胞疗法、免疫检查点抑制剂治疗等，但目前结直肠癌免疫治疗主要集中于免疫检查点抑制剂(PD-1/PD-L1及CTLA-4抑制剂等)。自从PD-1/PD-L1抑制剂在dMMR/MSI-H晚期结直肠癌患者上表现出较好的疗效以来，免疫检查点抑制剂在结直肠癌领域获得了越来越多的关注，治疗方案也从晚期后线治疗逐渐移至一线治疗或新辅助治疗并获得了成功，本文就近年来国内外结直肠癌免疫检查点治疗的研究进展作一综述。
Abstract:At present, immunotherapy is in full swing in the treatment of non-small cell lung cancer, melanoma, bladder cancer and other tumor species, and its treatment methods are also diverse, including tumor vaccine treatment, adoptive T cell therapy, immune checkpoint inhibitor treatment, etc, but current immunotherapy for colorectal cancer mainly focuses on immune checkpoint inhibitors (PD-1/PD-L1 and CTLA-4 inhibitors). Since PD-1/PD-L1 inhibitors have shown amazing efficacy in patients with dMMR/MSI-H advanced colorectal cancer, immune checkpoint inhibitors have gained more and more attention in the field of colorectal cancer, and the treatment options have gradually shifted from late line treatment to first-line treatment or neoadjuvant therapy, and have achieved success. This paper summarizes the research progress of immune checkpoint therapy on colorectal cancer.
-
Key words:
- Colorectal cancer /
- Immunotherapy /
- Immune checkpoint inhibitors
-
Competing interests: The authors declare that they have no competing interests.作者贡献曹奇华：文章内容构思、文献搜集、数据解释及文章撰写许燕波：文献搜集、协助文章撰写徐栋：文章的设计和指导
-
[1] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi: 10.3322/caac.21338
[2] Quiroga D, Lyerly HK, Morse MA. Deficient mismatch repair and the role of immunotherapy in metastatic colorectal cancer[J]. Curr Treat Options Oncol, 2016, 17(8): 41. doi: 10.1007/s11864-016-0414-4
[3] Le DT, Uram JN, Wang H, et al. Mismatch-repair deficiency predicts response of solid tumors to PD-1 blockade[J]. Science, 2017, 357(6349) : 409-413. doi: 10.1126/science.aan6733
[4] Gelsomino F, Barbolini M, Spallanzani A, et al. The evolving role of microsatellite instability in colorectal cancer: A review[J]. Cancer Treat Rev, 2016, 51: 19-26. doi: 10.1016/j.ctrv.2016.10.005
[5] Tougeron D, Fauquembergue E, Rouquette A, et al. Tumor infiltrating lymphocytes in colorectal cancers with microsatellite instability are correlated with the number and spectrum of frame shift mutations[J]. Mod Pathol, 2009, 22(9): 1186-1195. doi: 10.1038/modpathol.2009.80
[6] Smyrk TC, Watson P, Kaul K, et al. Tumor-infifiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma[J]. Cancer, 2001, 91(12): 2417-2422. doi: 10.1002/1097-0142(20010615)91:12<2417::AID-CNCR1276>3.0.CO;2-U
[7] 汤国军, 胡丛岗, 童骎, 等. 程序性死亡配体1在结直肠癌中的表达及作用[J]. 中国普通外科杂志, 2018, 27(6): 792-795. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWZ201806027.htm Tang GJ, Hu CG, Tong Q, et al. Expression and effect of programmed cell death ligand-1 in colorectal cancer[J]. Zhongguo Pu Tong Wai Ke Za Zhi, 2018, 27(6): 792-795. https://www.cnki.com.cn/Article/CJFDTOTAL-ZPWZ201806027.htm
[8] Gatalica Z, Snyder CL, Yeatts K, et al. Programmed death 1 (PD-1) lymphocytes and ligand (PD-L1) in colorectal cancer and their relationship to microsatellite instability status[EB/OL]. (2014-05-31). http://meetinglibrary.asco.org/content/133958-144.
[9] Le DT, Kim TW, Cutsem EV, et al. Phase Ⅱ Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164[J]. J Clin Oncol, 2020, 38(1): 11-19. doi: 10.1200/JCO.19.02107
[10] Fukuoka S, Hara H, Takahashi N, et al. Regorafenib Plus Nivolumab in Patients With Advanced Gastric or Colorectal Cancer: An Open-Label, Dose-Escalation, and Dose-Expansion Phase Ib Trial (REGONIVO, EPOC1603)[J]. J Clin Oncol, 2020, 38(18): 2053-2061. doi: 10.1200/JCO.19.03296
[11] Overman MJ, McDermott R, Leach JL, et al. Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study[J]. Lancet Oncol, 2017, 18(9): 1182-1191. doi: 10.1016/S1470-2045(17)30422-9
[12] Overman MJ, Lonardi S, Wang KYM, et al. Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer[J]. J Clin Oncol, 2018, 36(8): 773-779. doi: 10.1200/JCO.2017.76.9901
[13] André T, Shiu KK, Kim TW, et al. Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer[J]. N Engl J Med, 2020, 383(23): 2207-2218. doi: 10.1056/NEJMoa2017699
[14] Forde PM, Chaft JE, Smith KN, et al. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer[J]. N Engl J Med, 2018, 378(21): 1976-1986. doi: 10.1056/NEJMoa1716078
[15] Cascone T, William WN, Weissferdt A, et al. Neoadjuvant nivolumab (N) or nivolumab plus ipilimumab (NI) for resectable non-small cell lung cancer (NSCLC)[J]. J Clin Oncol, 2018, 29 (suppl_ 8): viii738. http://www.sciencedirect.com/science/article/pii/S0923753419504501
[16] Provencio-Pulla M, Nadal-Alforja E, Cobo M, et al. Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial[EB/OL]. (2020-09-24). https://sci-hub.se/10.1016/S1470-2045(20)30453-8
[17] Huang AC, Orlowski RJ, Xu X, et al. A single dose of neoadjuvant PD-1 blockade predicts clinical outcomes in resectable melanoma[J]. Nat Med, 2019, 25(3): 454-461. doi: 10.1038/s41591-019-0357-y
[18] Hanna GJ, Adkins DR, Zolkind P, et al. Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma[J]. Oral Oncol, 2017, 73: 65-69. doi: 10.1016/j.oraloncology.2017.08.008
[19] Cloughesy TF, Mochizuki AY, Orpilla JR, et al. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma[J]. Nat Med, 2019, 25(3): 477-486. doi: 10.1038/s41591-018-0337-7
[20] Necchi A, Anichini A, Raggi D, et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase Ⅱ Study[J]. J Clin Oncol, 2018, 36(34): 3353-3360. doi: 10.1200/JCO.18.01148
[21] Keung EZ, Ukponmwan EU, Cogdill AP, et al. The rationale and emerging use of neoadjuvant immune checkpoint blockade for solid malignancies[J]. Ann Surg Oncol, 2018, 25(7): 1814-1827. doi: 10.1245/s10434-018-6379-8
[22] Melero I, Berraondo P, Rodriguez-Ruiz ME, et al. Making the most of cancer surgery with neoadjuvant immunotherapy[J]. Cancer Discov, 2016, 6(12): 1312-1314. doi: 10.1158/2159-8290.CD-16-1109
[23] Chalabi M, Fanchi LF, Dijkstra KK, et al. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers[J]. Nat Med, 2020, 26(4): 566-576. doi: 10.1038/s41591-020-0805-8
[24] Cottrell TR, Thompson ED, Forde PM, et al. Pathologic features of response to neoadjuvant anti-PD-1 in resected non-small-cell lung carcinoma: a proposal for quantitative immune-related pathologic response criteria (irPRC)[J]. Ann Oncol, 2018, 29(8): 1853-1860. doi: 10.1093/annonc/mdy218
[25] Thommen DS, Koelzer VH, Petra H, et al. A transcriptionally and functionally distinct PD-1+ CD8+ T cell pool with predictive potential in non-small-cell lung cancer treated with PD-1 blockade[J]. Nat Med, 2018, 24(7): 994-1004. doi: 10.1038/s41591-018-0057-z
[26] 刘兆辉, 张磊, 徐小平, 等. 转移性大肠癌免疫治疗的现状[J]. 肿瘤防治研究, 2020, 47(12): 925-930. doi: 10.3971/j.issn.1000-8578.2020.20.0864 Liu ZH, Zhang L, Xu XP, et al. Current Status of Immunotherapy for Metastatic Colorectal Cancer[J]. Zhong Liu Fang Zhi Yan Jiu, 2020, 47(12): 925-930. doi: 10.3971/j.issn.1000-8578.2020.20.0864
计量
- 文章访问数: 2305
- HTML全文浏览量: 747
- PDF下载量: 1542
下载:
