Disrupting Siglec-mediated interactions to develop immunotherapies for cancer treatment.

IF 4.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

Expert Opinion on Therapeutic Targets Pub Date : 2025-09-01 Epub Date: 2025-09-09 DOI:10.1080/14728222.2025.2557281

Heinz Läubli, Ajit Varki

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引用次数: 0

Abstract

Introduction: Recent advances in cancer immunotherapy have improved patient outcomes, even in advanced stages of the disease. However, the effectiveness of current cancer immunotherapies remains limited to a small subset of patients because of resistance and an immunosuppressive tumor microenvironment.

Areas covered: Research performed during the last years have identified immunosuppressive interactions between sialic acid-containing glycans and sialic acid-binding immunoglobulin-like lectin (Siglec) receptors as a potential new, targetable pathway to overcome resistance to immunotherapy. In addition, activatory Siglecs could be engaged to enhance anti-tumor immunity. In this review, we summarize accumulating preclinical evidence demonstrating the immunosuppressive role of sialoglycan-Siglec interactions in cancer. Additionally, we provide an overview of potential therapeutic strategies aimed at disrupting this immunosuppressive axis, including interventions currently being evaluated in early-phase clinical trials.

Expert opinion: Preclinical data strongly suggests that disrupting sialic acid-Siglec interactions could significantly improve cancer immunotherapy, in particular by changing the immunosuppressive microenvironment. Further biological understanding is needed to successfully develop new therapeutics. First trials are running that target these interactions and will hopefully inform, which patients are benefitting from this treatment.

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破坏siglecl介导的相互作用以开发用于癌症治疗的免疫疗法。

导读：癌症免疫治疗的最新进展改善了患者的预后，即使是在疾病的晚期。然而，由于耐药和免疫抑制肿瘤微环境，目前癌症免疫疗法的有效性仍然局限于一小部分患者。涵盖领域：过去几年进行的研究已经确定了含唾液酸聚糖和唾液酸结合免疫球蛋白样凝集素（Siglec）受体之间的免疫抑制相互作用，作为克服免疫治疗耐药的潜在新途径。此外，活化Siglecs可以增强抗肿瘤免疫。在这篇综述中，我们总结了涎聚糖- siglec相互作用在癌症中免疫抑制作用的临床前证据。此外，我们还概述了旨在破坏这种免疫抑制轴的潜在治疗策略，包括目前正在早期临床试验中评估的干预措施。专家意见：临床前数据强烈表明，破坏唾液酸- siglec相互作用可以显著改善癌症免疫治疗，特别是通过改变免疫抑制微环境。要成功开发新的治疗方法，需要进一步了解生物学。针对这些相互作用的第一次试验正在进行，并有望告知哪些患者将从这种治疗中受益。

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

Expert Opinion on Therapeutic Targets 医学-药学

CiteScore

8.90

自引率

1.70%

发文量

审稿时长

3 months

期刊介绍： The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.