免疫检查点抑制剂相关结肠炎的发病机制
Pathogenesis of Immune Checkpoint Inhibitor-Mediated Colitis
摘要: 免疫检查点抑制剂(ICI)的临床应用是恶性肿瘤治疗史上飞跃式的进展，它显著改善了患者的生存率，在非小细胞肺癌、胃癌等多种恶性肿瘤中提供了巨大的临床益处。但与此同时，ICI也可通过诱发全身免疫系统的激活而导致免疫相关不良反应(irAE)，本文着重对免疫检查点抑制剂相关结肠炎发病机制的研究进展进行综述，以期早期预测、识别发生IMC的高危人群，并据此给予肿瘤患者合理的治疗方案。
Abstract: The clinical application of immune checkpoint inhibitors (ICI) is a leap forward in the history of ma-lignant tumor treatment. It has significantly improved the survival rate of patients and provided great clinical benefits in various malignant tumors such as non-small cell lung cancer and gastric cancer. However, at the same time, ICI can also induce immune-related adverse events (irAE) by inducing the activation of the systemic immune system. This article focuses on the research pro-gress of the pathogenesis of immune checkpoint inhibitor-mediated colitis, in order to predict and identify the occurrence of high-risk groups of IMC, and accordingly provide reasonable treatment plans for tumor patients.
文章引用：郭宇扬, 王嫣琦, 白宇, 刘丹平. 免疫检查点抑制剂相关结肠炎的发病机制[J]. 临床医学进展, 2022, 12(10): 8888-8893. https://doi.org/10.12677/ACM.2022.12101283

参考文献

[1] Postow, M.A., Sidlow, R. and Hellmann, M.D. (2018) Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. The New England Journal of Medicine, 378, 158-168. [Google Scholar] [CrossRef] 
[2] Khoja, L., Day, D., et al. (2017) Tumour- and Class-Specific Pat-terns of Immune-Related Adverse Events of Immune Checkpoint Inhibitors: A Systematic Review. Annals of Oncology, 28, 2377-2385. [Google Scholar] [CrossRef] [PubMed]
[3] Wang, D.Y., Salem, J.E., Cohen, J.V., et al. (2018) Fatal Toxic Ef-fects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis. JAMA Oncology, 4, 1721-1728. [Google Scholar] [CrossRef] [PubMed]
[4] Bauché, D., Mauze, S., Kochel, C., et al. (2020) Antitumor Effi-cacy of Combined CTLA4/PD-1 Blockade without Intestinal Inflammation Is Achieved by Elimination of FcγR Interac-tions. Journal for ImmunoTherapy of Cancer, 8, e001584. [Google Scholar] [CrossRef] [PubMed]
[5] Han, X., Ding, S., Jiang, H., et al. (2021) Roles of Macrophages in the Development and Treatment of Gut Inflammation. Fron-tiers in Cell and Developmental Biology, 9, Article ID: 625423. [Google Scholar] [CrossRef] [PubMed]
[6] Mishima, Y. and Sartor, R.B. (2020) Manipulating Resident Micro-biota to Enhance Regulatory Immune Function to Treat Inflammatory Bowel Diseases. Journal of Gastroenterology, 55, 4-14. [Google Scholar] [CrossRef] [PubMed]
[7] Omenetti, S. and Pizarro, T.T. (2015) The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome. Frontiers in Immunology, 6, Article No. 639. [Google Scholar] [CrossRef] [PubMed]
[8] Chaudhry, A., Samstein, R.M., Treuting, P., et al. (2011) Interleu-kin-10 Signaling in Regulatory T Cells Is Required for Suppression of Th17 Cell-Mediated Inflammation. Immunity, 34, 566-578. [Google Scholar] [CrossRef] [PubMed]
[9] Sasson, S.C., Zaunders, J.J., Nahar, K., et al. (2020) Muco-sal-Associated Invariant T (MAIT) Cells Are Activated in the Gastrointestinal Tissue of Patients with Combination Ipilimumab and Nivolumab Therapy-Related Colitis in a Pathology Distinct from Ulcerative Colitis. Clinical & Experi-mental Immunology, 202, 335-352. [Google Scholar] [CrossRef] [PubMed]
[10] Belkaid, Y. and Hand, T.W. (2014) Role of the Microbiota in Immunity and Inflammation. Cell, 157, 121-141. [Google Scholar] [CrossRef] [PubMed]
[11] Abu-Sbeih, H., Herrera, L.N., Tang, T., et al. (2019) Correction to: Impact of Antibiotic Therapy on the Development and Response to Treatment of Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis. Journal for ImmunoTherapy of Cancer, 7, Article No. 352. [Google Scholar] [CrossRef] [PubMed]
[12] Sun, S., Luo, L., Liang, W., et al. (2020) Bifidobacterium Alters the Gut Microbiota and Modulates the Functional Metabolism of T Regulatory Cells in the Context of Immune Check-point Blockade. Proceedings of the National Academy of Sciences of the United States of America, 117, 27509-27515. [Google Scholar] [CrossRef] [PubMed]
[13] Wang, T., Zheng, N., Luo, Q., et al. (2019) Probiotics Lactobacillus reuteri Abrogates Immune Checkpoint Blockade-Associated Colitis by Inhibiting Group 3 Innate Lymphoid Cells. Fron-tiers in Immunology, 10, Article No. 1235. [Google Scholar] [CrossRef] [PubMed]
[14] Wang, F., Yin, Q., Chen, L., et al. (2018) Bifidobacterium Can Mitigate Intestinal Immunopathology in the Context of CTLA-4 Blockade. Proceedings of the National Academy of Sci-ences of the United States of America, 115, 157-161. [Google Scholar] [CrossRef] [PubMed]
[15] Jinnohara, T., Kanaya, T., Hase, K., et al. (2017) IL-22BP Dictates Characteristics of Peyer’s Patch Follicle-Associated Epithelium for Antigen Uptake. Journal of Experimental Medicine, 214, 1607-1618. [Google Scholar] [CrossRef] [PubMed]
[16] Park, H.J., Lee, S.W., Van Kaer, L., et al. (2021) CD1d-Dependent iNKT Cells Control DSS-Induced Colitis in a Mouse Model of IFNγ-Mediated Hyperinflammation by Increasing IL22-Secreting ILC3 Cells. International Journal of Molecular Sciences, 22, Article No. 1250. [Google Scholar] [CrossRef] [PubMed]
[17] Mortha, A., Chudnovskiy, A., Hashimoto, D., et al. (2014) Microbio-ta-Dependent Crosstalk between Macrophages and ILC3 Promotes Intestinal Homeostasis. Science, 343, Article ID: 1249288. [Google Scholar] [CrossRef] [PubMed]
[18] Fasanello, M.K., Robillard, K.T., Boland, P.M., et al. (2020) Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis. ACG Case Reports Journal, 7, e00360. [Google Scholar] [CrossRef] [PubMed]
[19] Coutzac, C., Adam, J., Soularue, E., et al. (2017) Colon Im-mune-Related Adverse Events: Anti-CTLA-4 and Anti-PD-1 Blockade Induce Distinct Immunopathological Entities. Journal of Crohn’s and Colitis, 11, 1238-1246. [Google Scholar] [CrossRef] [PubMed]
[20] Zhou, C.B., Zhou, Y.L. and Fang, J.Y. (2021) Gut Microbiota in Can-cer Immune Response and Immunotherapy. Trends in Cancer, 7, 647-660. [Google Scholar] [CrossRef] [PubMed]
[21] Kurki, M., Gilbert, S., Mishina, K., et al. (2021) Digital Mental Health Literacy-Program for the First-Year Medical Students’ Wellbeing: A One Group Quasi-Experimental Study. BMC Medical Education, 21, Article No. 563. [Google Scholar] [CrossRef] [PubMed]
[22] Ding, S.M., Lu, A.L., Zhang, W., et al. (2018) The Role of Cancer-Associated Fibroblast MRC-5 in Pancreatic Cancer. Journal of Cancer, 9, 614-628. [Google Scholar] [CrossRef] [PubMed]
[23] Zhang, S., Wang, L., Li, M., et al. (2021) The PD-1/PD-L Pathway in Rheumatic Diseases. Journal of the Formosan Medical Association, 120, 48-59. [Google Scholar] [CrossRef] [PubMed]
[24] Prakhar, P., Alvarez-DelValle, J., Keller, H., et al. (2021) The Small Intestine Epithelium Exempts Foxp3+ Tregs from Their IL-2 Requirement for Homeostasis and Effector Function. JCI Insight, 6, e149656. [Google Scholar] [CrossRef] [PubMed]
[25] Danylesko, I., Bukauskas, A., Paulson, M., et al. (2019) Anti-α4β7 Integrin Monoclonal Antibody (Vedolizumab) for the Treatment of Steroid-Resistant Severe Intestinal Acute Graft-versus-Host Disease. Bone Marrow Transplantation, 54, 987-993. [Google Scholar] [CrossRef] [PubMed]
[26] Zou, F., Faleck, D., Thomas, A., et al. (2021) Efficacy and Safety of Vedolizumab and Infliximab Treatment for Immune-Mediated Diarrhea and Colitis in Patients with Cancer: A Two-Center Observational Study. Journal for ImmunoTherapy of Cancer, 9, e003277. [Google Scholar] [CrossRef] [PubMed]
[27] Uemura, M., Trinh, V.A., Haymaker, C., et al. (2016) Selective In-hibition of Autoimmune Exacerbation while Preserving the Anti-Tumor Clinical Benefit Using IL-6 Blockade in a Patient with Advanced Melanoma and Crohn’s Disease: A Case Report. Journal of Hematology & Oncology, 9, Article No. 81. [Google Scholar] [CrossRef] [PubMed]
[28] Johnson, D., Patel, A.B., Uemura, M.I., et al. (2019) IL17A Blockade Successfully Treated Psoriasiform Dermatologic Toxicity from Immunotherapy. Cancer Immunology Research, 7, 860-865. [Google Scholar] [CrossRef] 
[29] Eksin, M.A., Erden, A., Güven, S.C., et al. (2022) Secuki-numab in the Treatment of Psoriatic Arthritis or Ankylosing Spondyloarthritis with Multiple Sclerosis: A Case Series with Literature Review. Immunotherapy, 14, 401-408. [Google Scholar] [CrossRef] [PubMed]
[30] Shaffer, S.R., Traboulsi, C., Krugliak Cleveland, N., et al. (2021) Combining Cyclosporine with Ustekinumab in Acute Severe Ulcerative Colitis. ACG Case Reports Journal, 8, e00604. [Google Scholar] [CrossRef] [PubMed]
[31] Nguyen, T.T., Ramsay, L., Ahanfeshar-Adams, M., et al. (2021) Mutations in the IFNγ-JAK-STAT Pathway Causing Resistance to Immune Checkpoint Inhibitors in Melanoma Increase Sensitivity to Oncolytic Virus Treatment. Clinical Cancer Research, 27, 3432-3442. [Google Scholar] [CrossRef] 
[32] Que, J., Van Oerle, R., Albersheim, S., et al. (2021) The Effect of Daily Probiotics on the Incidence and Severity of Necrotizing Enterocolitis in Infants with Very Low Birth Weight. Canadian Journal of Surgery, 64, E644-E649. [Google Scholar] [CrossRef] [PubMed]
[33] Routy, B., Le Chatelier, E., Derosa, L., et al. (2018) Gut Microbiome In-fluences Efficacy of PD-1-Based Immunotherapy against Epithelial Tumors. Science, 359, 91-97. [Google Scholar] [CrossRef] [PubMed]

为你推荐