实用医学杂志 ›› 2024, Vol. 40 ›› Issue (9): 1314-1319.doi: 10.3969/j.issn.1006-5725.2024.09.023
收稿日期:
2024-01-09
出版日期:
2024-05-10
发布日期:
2024-05-15
通讯作者:
孙旭,刘怀民
E-mail:zlyysunxu4137@zzu.edu.cn;huaiminliu@sina.com
基金资助:
Xiaona MENG,Xu SUN(),Huaimin LIU(
)
Received:
2024-01-09
Online:
2024-05-10
Published:
2024-05-15
Contact:
Xu SUN,Huaimin LIU
E-mail:zlyysunxu4137@zzu.edu.cn;huaiminliu@sina.com
摘要:
免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)包括细胞毒性T淋巴细胞相关蛋白4(cytotoxic T-lymphocyte-associated protein 4, CTLA-4)抑制剂和程序性死亡受体1(programmed cell death receptor 1, PD-1)抑制剂及其配体1(programmed death-ligand 1, PD-L1)抑制剂改变了很多恶性肿瘤患者的临床结局,成为目前最重要的抗肿瘤手段。随着免疫治疗的广泛应用,ICIs 诱导的免疫相关不良事件(immune-related adverse events, irAEs)逐渐引起临床重视,其中ICI相关结肠炎已成为胃肠道系统最常见的不良事件。本文通过对ICI相关结肠炎的流行病学、发病机制及临床诊治等领域进展进行阐述,旨在为临床医师及时鉴别和诊疗ICI 相关结肠炎提供参考。
中图分类号:
孟肖娜,孙旭,刘怀民. 免疫检查点抑制剂相关结肠炎的研究进展[J]. 实用医学杂志, 2024, 40(9): 1314-1319.
Xiaona MENG,Xu SUN,Huaimin LIU. Advances in the study of immune checkpoint inhibitors⁃related colitis[J]. The Journal of Practical Medicine, 2024, 40(9): 1314-1319.
1 |
ZHANG B, WU Q, ZHOU Y L, et al. Immune-related adverse events from combination immunotherapy in cancer patients: A comprehensive meta-analysis of randomized controlled trials [J]. Inte Immunopharmacol, 2018, 63: 292-298. doi:10.1016/j.intimp.2018.08.014
doi: 10.1016/j.intimp.2018.08.014 |
2 |
PARENTE P, MAIORANO B A, CIARDIELLO D, et al. Clinic, Endoscopic and Histological Features in Patients Treated with ICI Developing GI Toxicity: Some News and Reappraisal from a Mono-Institutional Experience [J]. Diagnostics (Basel, Switzerland), 2022, 12(3): 685-697. doi:10.3390/diagnostics12030685
doi: 10.3390/diagnostics12030685 |
3 |
LARKIN J, HODI F S, WOLCHOK J D. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma [J]. N Engl J Med, 2015, 373(13): 1270-1271. doi:10.1056/nejmc1509660
doi: 10.1056/nejmc1509660 |
4 |
RAMOS-CASALS M, BRAHMER J R, CALLAHAN M K, et al. Immune-related adverse events of checkpoint inhibitors [J]. Nat Rev Dis Primers, 2020, 6(1): 38-90. doi:10.1038/s41572-020-0160-6
doi: 10.1038/s41572-020-0160-6 |
5 |
SOULARUE E, LEPAGE P, COLOMBEL J F, et al. Enterocolitis due to immune checkpoint inhibitors: a systematic review [J]. Gut, 2018, 67(11): 2056-2067. doi:10.1136/gutjnl-2018-316948
doi: 10.1136/gutjnl-2018-316948 |
6 |
WEBER J S, KÄHLER K C, HAUSCHILD A. Management of immune-related adverse events and kinetics of response with ipilimumab [J]. J Clin Oncol, 2012, 30(21): 2691-2697. doi:10.1200/jco.2012.41.6750
doi: 10.1200/jco.2012.41.6750 |
7 |
ASCIERTO P A, DEL VECCHIO M, ROBERT C, et al. Ipilimumab 10 mg/kg versus ipilimumab 3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, double-blind, multicentre, phase 3 trial [J]. Lancet Oncol, 2017, 18(5): 611-622. doi:10.1016/s1470-2045(17)30231-0
doi: 10.1016/s1470-2045(17)30231-0 |
8 | PAGAN A, ARROYO-MARTINEZ Y M, TANDON A, et al. Immune Checkpoint Inhibitor-Induced Acute Pancreatitis and Colitis [J]. Cureus, 2020, 12(6): e8613-e8617. |
9 |
KELLY-GOSS M R, BADRAN Y R, DOUGAN M. Update on Immune Checkpoint Inhibitor Enterocolitis [J]. Curr Gastroenterol Rep, 2022, 24(12): 171-181. doi:10.1007/s11894-022-00852-7
doi: 10.1007/s11894-022-00852-7 |
10 |
ABU-SBEIH H, FALECK D M, RICCIUTI B, et al. Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease [J]. J Clin Oncol, 2020, 38(6): 576-583. doi:10.1200/jco.19.01674
doi: 10.1200/jco.19.01674 |
11 |
WEINGARDEN A R, GUBATAN J, SINGH S, et al. Immune checkpoint inhibitor-mediated colitis is associated with cancer overall survival [J]. World J Gastroenterol, 2022, 28(39): 5750-5763. doi:10.3748/wjg.v28.i39.5750
doi: 10.3748/wjg.v28.i39.5750 |
12 |
ROUTY B, GOPALAKRISHNAN V, DAILLÈRE R, et al. The gut microbiota influences anticancer immunosurveillance and general health [J]. Nat Rev Clin Oncol, 2018, 15(6): 382- 396. doi:10.1038/s41571-018-0006-2
doi: 10.1038/s41571-018-0006-2 |
13 |
ABU-SBEIH H, HERRERA L N, TANG T, et al. Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis [J]. J Immunother Cancer, 2019, 7(1): 242-253. doi:10.1186/s40425-019-0714-x
doi: 10.1186/s40425-019-0714-x |
14 |
HASAN ALI O, BERNER F, BOMZE D, et al. Human leukocyte antigen variation is associated with adverse events of checkpoint inhibitors [J]. Eur J Cancer, 2019, 107: 8-14. doi:10.1016/j.ejca.2018.11.009
doi: 10.1016/j.ejca.2018.11.009 |
15 |
WÖLFFER M, BATTKE F, SCHULZE M, et al. Biomarkers Associated with Immune-Related Adverse Events under Checkpoint Inhibitors in Metastatic Melanoma [J]. Cancers(Basel), 2022, 14(2): 302-323. doi:10.3390/cancers14020302
doi: 10.3390/cancers14020302 |
16 |
OKIYAMA N, TANAKA R. Immune-related adverse events in various organs caused by immune checkpoint inhibitors [J]. Allergol Int, 2022, 71(2): 169-178. doi:10.1016/j.alit.2022.01.001
doi: 10.1016/j.alit.2022.01.001 |
17 |
ZHOU X, CHEN X, HAN L, et al. Mechanisms underlying immune-related adverse events during checkpoint immunotherapy [J]. Clin Sci, 2022, 136(10): 771-785. doi:10.1042/cs20210042
doi: 10.1042/cs20210042 |
18 |
MILLING L, ZHANG Y, IRVINE D J. Delivering safer immunotherapies for cancer [J]. Adv Drug Deliv Rev, 2017, 114: 79-101. doi:10.1016/j.addr.2017.05.011
doi: 10.1016/j.addr.2017.05.011 |
19 |
YANG H, YAO Z, ZHOU X, et al. Immune-related adverse events of checkpoint inhibitors: Insights into immunological dysregulation [J]. Clin Immunol, 2020, 213: 108377-108387. doi:10.1016/j.clim.2020.108377
doi: 10.1016/j.clim.2020.108377 |
20 |
KUMAR P, SAINI S, PRABHAKAR B S. Cancer immunotherapy with check point inhibitor can cause autoimmune adverse events due to loss of Treg homeostasis [J]. Semin Cancer Biol, 2020, 64: 29-35. doi:10.1016/j.semcancer.2019.01.006
doi: 10.1016/j.semcancer.2019.01.006 |
21 |
KUMAR P, BHATTACHARYA P, PRABHAKAR B S. A comprehensive review on the role of co-signaling receptors and Treg homeostasis in autoimmunity and tumor immunity [J]. J Autoimmun, 2018, 95: 77-99. doi:10.1016/j.jaut.2018.08.007
doi: 10.1016/j.jaut.2018.08.007 |
22 |
LUOMA A M, SUO S, WILLIAMS H L, et al. Molecular Pathways of Colon Inflammation Induced by Cancer Immunotherapy [J]. Cell, 2020, 182(3): 655-671. doi:10.1016/j.cell.2020.06.001
doi: 10.1016/j.cell.2020.06.001 |
23 |
BLASCHITZ C, RAFFATELLU M. Th17 cytokines and the gut mucosal barrier [J]. J Clin Immunol, 2010, 30(2): 196-203. doi:10.1007/s10875-010-9368-7
doi: 10.1007/s10875-010-9368-7 |
24 |
WESTDORP H, SWEEP M W D, GORRIS M A J, et al. Mechanisms of Immune Checkpoint Inhibitor-Mediated Colitis [J]. Front Immunol, 2021, 12: 768957. doi:10.3389/fimmu.2021.768957
doi: 10.3389/fimmu.2021.768957 |
25 |
AL-QADAMI G, VAN SEBILLE Y, LE H, et al. Gut microbiota: implications for radiotherapy response and radiotherapy-induced mucositis [J]. Expert Rev Gastroenterol Hepatol, 2019, 13(5): 485-496. doi:10.1080/17474124.2019.1595586
doi: 10.1080/17474124.2019.1595586 |
26 |
SUN S, LUO L, LIANG W, et al. Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade [J]. Pro Nat Acad Sci U S A, 2020, 117(44): 27509-27515. doi:10.1073/pnas.1921223117
doi: 10.1073/pnas.1921223117 |
27 |
CHAPUT N, LEPAGE P, COUTZAC C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab [J]. Ann Oncol, 2017, 28(6): 1368-1379. doi:10.1093/annonc/mdx108
doi: 10.1093/annonc/mdx108 |
28 |
TAO R, DE ZOETEN E F, OZKAYNAK E, et al. Deacetylase inhibition promotes the generation and function of regulatory T cells [J]. Nat Med, 2007, 13(11): 1299-1307. doi:10.1038/nm1652
doi: 10.1038/nm1652 |
29 |
RENGA G, NUNZI E, PARIANO M, et al. Optimizing therapeutic outcomes of immune checkpoint blockade by a microbial tryptophan metabolite [J]. J Immunother Cancer, 2022, 10(3): e003725. doi:10.1136/jitc-2021-003725
doi: 10.1136/jitc-2021-003725 |
30 |
FRIEDMAN C F, PROVERBS-SINGH T A, POSTOW M A. Treatment of the Immune-Related Adverse Effects of Immune Checkpoint Inhibitors: A Review [J]. JAMA Oncol, 2016, 2(10): 1346-1353. doi:10.1001/jamaoncol.2016.1051
doi: 10.1001/jamaoncol.2016.1051 |
31 |
DEPUTY M, DEVANABOINA R, BAKIR I AL, et al. The role of faecal calprotectin in the diagnosis of inflammatory bowel disease [J]. BMJ, 2023, 380: e068947. doi:10.1136/bmj-2021-068947
doi: 10.1136/bmj-2021-068947 |
32 |
ZOU F, WANG X, GLITZA OLIVA I C, et al. Fecal calprotectin concentration to assess endoscopic and histologic remission in patients with cancer with immune-mediated diarrhea and colitis [J]. J Immunother Cancer, 2021, 9(1): e002058. doi:10.1136/jitc-2020-002058
doi: 10.1136/jitc-2020-002058 |
33 |
NISHIDA T, IIJIMA H, ADACHI S. Immune checkpoint inhibitor-induced diarrhea/colitis: Endoscopic and pathologic findings [J]. World J Gastrointest Pathophysiol, 2019, 10(2): 17-28. doi:10.4291/wjgp.v10.i2.17
doi: 10.4291/wjgp.v10.i2.17 |
34 |
WANG Y, ABU-SBEIH H, MAO E, et al. Endoscopic and Histologic Features of Immune Checkpoint Inhibitor-Related Colitis [J]. Inflamm Bowel Dis, 2018, 24(8): 1695-1705. doi:10.1093/ibd/izy104
doi: 10.1093/ibd/izy104 |
35 |
DOUGAN M, WANG Y, RUBIO-TAPIA A, et al. AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review [J]. Gastroenterology, 2021, 160(4): 1384-1393. doi:10.1053/j.gastro.2020.08.063
doi: 10.1053/j.gastro.2020.08.063 |
36 |
HUGHES M S, MOLINA G E, CHEN S T, et al. Budesonide treatment for microscopic colitis from immune checkpoint inhibitors [J]. J Immunother Cancer, 2019, 7(1): 292-302. doi:10.1186/s40425-019-0756-0
doi: 10.1186/s40425-019-0756-0 |
37 |
GARCIA-NEUER M, MARMARELIS M E, JANGI S R, et al. Diagnostic Comparison of CT Scans and Colonoscopy for Immune-Related Colitis in Ipilimumab-Treated Advanced Melanoma Patients [J]. Cancer Immunol Res, 2017, 5(4): 286-291. doi:10.1158/2326-6066.cir-16-0302
doi: 10.1158/2326-6066.cir-16-0302 |
38 | Common terminology criteria for adverse events (Ctcae V 5.0) [EB/OL]. |
39 |
BADRAN Y R, SHIH A, LEET D, et al. Immune checkpoint inhibitor-associated celiac disease [J]. J Immunother Cancer, 2020, 8(1): e00958. doi:10.1136/jitc-2020-000958
doi: 10.1136/jitc-2020-000958 |
40 |
SINGH B P, MARSHALL J L, HE A R. Workup and Management of Immune-Mediated Colitis in Patients Treated with Immune Checkpoint Inhibitors [J]. Oncologist, 2020, 25(3): 197-202. doi:10.1634/theoncologist.2018-0304
doi: 10.1634/theoncologist.2018-0304 |
41 |
KIPARIZOSKA S, MURPHY M E, MATTAR M C. Check this out: treatment paradigms in immune-checkpoint inhibitor colitis [J]. Curr Opin Gastroenterol, 2023, 39(1): 43-49. doi:10.1097/mog.0000000000000892
doi: 10.1097/mog.0000000000000892 |
42 |
NICOLAIDES S, BOUSSIOUTAS A. Immune-Related Adverse Events of the Gastrointestinal System [J]. Cancers(Basel), 2023, 15(3): 691-703. doi:10.3390/cancers15030691
doi: 10.3390/cancers15030691 |
43 |
BADRAN Y R, COHEN J V, BRASTIANOS P K, et al. Concurrent therapy with immune checkpoint inhibitors and TNF-α blockade in patients with gastrointestinal immune-related adverse events [J]. J Immunother Cancer, 2019, 7(1): 226-237. doi:10.1186/s40425-019-0711-0
doi: 10.1186/s40425-019-0711-0 |
44 |
ZOU F, FALECK D, THOMAS A, et al. Efficacy and safety of vedolizumab and infliximab treatment for immune-mediated diarrhea and colitis in patients with cancer: a two-center observational study [J]. J Immunother Cancer, 2021, 9(11): e003277. doi:10.1136/jitc-2021-003277
doi: 10.1136/jitc-2021-003277 |
45 |
DORA D, BOKHARI S M Z, ALOSS K, et al. Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy [J]. Int J Mol Sci, 2023, 24(3): 2769-2795. doi:10.3390/ijms24032769
doi: 10.3390/ijms24032769 |
46 |
MU A, MCDONALD D, JARMUSCH A K, et al. Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection [J]. Microbiome, 2021, 9(1): 92-100. doi:10.1186/s40168-021-01026-9
doi: 10.1186/s40168-021-01026-9 |
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