Disrupting neuro-immune feedback loops: novel targets to amplify cancer immunotherapy.

IF 2.3 4区医学 Q3 IMMUNOLOGY

Immunotherapy Pub Date : 2026-04-01 Epub Date: 2026-05-27 DOI:10.1080/1750743X.2026.2676456

Abbas Jafari, Kovsar Mohammadnezhadharmileh, Maryam Majidinia, Soheil Vazifedust, Ebrahim Mazloomi

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Abstract

Nervous system and immune system have tight interactions that modulate both nerves and immune cells' activities. The interplay between the nervous and immune systems within the tumor microenvironment is a critical yet underexplored determinant of cancer immunotherapy efficacy. This review presents a new model called the Neuro-Immune Feedback Loop, which suggests that two-way communication (like the immunosuppressive effects of norepinephrine and the influence of cytokines on nerve activity) creates self-perpetuating cycles that tumors use to avoid immune responses. We compile evidence regarding neurotransmitters (such as dopamine), neuropeptides (like CGRP) to suggest innovative strategies to disrupt the immune-nerve loops. The current review proposes that context-sensitive neuro-immune switches (for instance, the dual functions of GABA) and multi-target therapies (such as CRISPR-modified neurons combined with immune checkpoint inhibitors (ICIs) could enhance immunotherapy effectiveness. By connecting neuroscience with immunology and oncology, this review aims to provide a roadmap for overcoming resistance to immunotherapies, presenting testable ideas and a new approach for precision cancer treatment. Literature search: PubMed, Scopus, and Web of Science were searched for relevant studies published between January 2000 and March 2026, with emphasis on recent publications (2024-2026) related to neuro-immune interactions in cancer.

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破坏神经免疫反馈回路：扩大癌症免疫治疗的新靶点。

神经系统和免疫系统有密切的相互作用，调节神经和免疫细胞的活动。肿瘤微环境中神经系统和免疫系统之间的相互作用是影响肿瘤免疫治疗效果的关键因素，但尚未得到充分的研究。这篇综述提出了一个叫做神经-免疫反馈回路的新模型，该模型表明双向交流（如去甲肾上腺素的免疫抑制作用和细胞因子对神经活动的影响）创造了自我延续的循环，肿瘤利用这种循环来避免免疫反应。我们收集了有关神经递质（如多巴胺），神经肽（如CGRP）的证据，以提出创新的策略来破坏免疫-神经回路。目前的综述提出，上下文敏感的神经免疫开关（例如，GABA的双重功能）和多靶点治疗（例如crispr修饰的神经元与免疫检查点抑制剂（ICIs）联合）可以增强免疫治疗的有效性。通过将神经科学与免疫学和肿瘤学相结合，本综述旨在为克服免疫疗法的耐药性提供路线图，提出可测试的想法和精确治疗癌症的新方法。文献检索：检索PubMed、Scopus和Web of Science在2000年1月至2026年3月期间发表的相关研究，重点是最近发表的（2024-2026）与癌症中神经免疫相互作用相关的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunotherapy 医学-免疫学

CiteScore

5.00

自引率

3.60%

发文量

113

审稿时长

6-12 weeks

期刊介绍： Many aspects of the immune system and mechanisms of immunomodulatory therapies remain to be elucidated in order to exploit fully the emerging opportunities. Those involved in the research and clinical applications of immunotherapy are challenged by the huge and intricate volumes of knowledge arising from this fast-evolving field. The journal Immunotherapy offers the scientific community an interdisciplinary forum, providing them with information on the most recent advances of various aspects of immunotherapies, in a concise format to aid navigation of this complex field. Immunotherapy delivers essential information in concise, at-a-glance article formats. Key advances in the field are reported and analyzed by international experts, providing an authoritative but accessible forum for this vitally important area of research. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.