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JAK-STAT通路作为免疫检查点抑制剂诱导的结肠炎癌症患者的治疗策略:一项叙述性综述。

The JAK-STAT Pathway as a Therapeutic Strategy in Cancer Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Narrative Review.

作者信息

Gravina Antonietta Gerarda, Pellegrino Raffaele, Esposito Alfonso, Cipullo Marina, Romeo Mario, Palladino Giovanna, Iodice Patrizia, Federico Alessandro, Troiani Teresa

机构信息

Hepatogastroenterology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, Italy.

Oncology Division, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Via L. de Crecchio, 80138 Naples, Italy.

出版信息

Cancers (Basel). 2024 Jan 31;16(3):611. doi: 10.3390/cancers16030611.

Abstract

Immunotherapy has emerged as a pivotal component in the treatment of various malignancies, encompassing lung, skin, gastrointestinal, and head and neck cancers. The foundation of this therapeutic approach lies in immune checkpoint inhibitors (ICI). While ICIs have demonstrated remarkable efficacy in impeding the neoplastic progression of these tumours, their use may give rise to substantial toxicity, notably in the gastrointestinal domain, where ICI colitis constitutes a significant aspect. The optimal positioning of Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway inhibitors in the therapeutic management of ICI colitis remains unclear. Numerous reports have highlighted notable improvements in ICI colitis through the application of pan-JAK-STAT inhibitors, with tofacitinib, in particular, reporting evident clinical remission of colitis. The precise mechanism by which JAK-STAT inhibitors may impact the pathogenetic process of ICI colitis remains inadequately understood. However, there is speculation regarding their potential role in modulating memory resident CD8 T lymphocytes. The elucidation of this mechanism requires further extensive and robust evidence, and ongoing JAK-STAT-based trials are anticipated to contribute valuable insights.

摘要

免疫疗法已成为治疗各种恶性肿瘤的关键组成部分,包括肺癌、皮肤癌、胃肠道癌和头颈癌。这种治疗方法的基础是免疫检查点抑制剂(ICI)。虽然ICI在阻碍这些肿瘤的肿瘤进展方面已显示出显著疗效,但其使用可能会引起严重毒性,特别是在胃肠道领域,其中ICI结肠炎是一个重要方面。Janus激酶(JAK)-信号转导和转录激活因子(STAT)途径抑制剂在ICI结肠炎治疗管理中的最佳定位仍不清楚。许多报告强调了通过应用泛JAK-STAT抑制剂,特别是托法替布,ICI结肠炎有显著改善,报告显示结肠炎明显临床缓解。JAK-STAT抑制剂可能影响ICI结肠炎发病过程的确切机制仍未得到充分理解。然而,有人推测它们在调节记忆驻留CD8 T淋巴细胞方面的潜在作用。这一机制的阐明需要进一步广泛而有力的证据,预计正在进行的基于JAK-STAT的试验将提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1804/10854551/82e7cc1f095a/cancers-16-00611-g001.jpg

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