Dumbrava Ecaterina Elena, Ben Haj Frej Khaoula, Sharon Elad, Tawbi Hussein
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA; email:
University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Annu Rev Med. 2025 Jan;76(1):189-205. doi: 10.1146/annurev-med-080222-100847. Epub 2025 Jan 16.
Immune checkpoint blockade targeting the novel targets of the lymphocyte activation gene 3 (LAG3) and the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) has marked a significant advancement in oncology, offering new therapeutic opportunities to fight diverse malignancies. This review covers the biological basis and clinical application of LAG3 and TIGIT inhibitors, highlighting pivotal trials and therapeutic outcomes. We underscore the use of dual therapy immune checkpoint blockade in enhancing antitumor immunity, particularly in settings where monotherapy has shown limited efficacy. Additionally, we address the emerging challenges such as treatment resistance and adverse effects. We explore the strategic integration of LAG3 and TIGIT blockade within the broader immunotherapy landscape, emphasizing innovative combinations and the quest for predictive biomarkers to optimize patient selection and treatment efficacy.
针对淋巴细胞激活基因3（LAG3）和具有Ig及基于免疫受体酪氨酸抑制基序结构域的T细胞免疫受体（TIGIT）这些新靶点的免疫检查点阻断疗法，在肿瘤学领域取得了重大进展，为对抗多种恶性肿瘤提供了新的治疗机会。本综述涵盖了LAG3和TIGIT抑制剂的生物学基础及临床应用，重点介绍了关键试验和治疗结果。我们强调使用双重免疫检查点阻断疗法来增强抗肿瘤免疫力，尤其是在单药治疗疗效有限的情况下。此外，我们还讨论了诸如治疗耐药性和不良反应等新出现的挑战。我们探讨了在更广泛的免疫治疗格局中LAG3和TIGIT阻断的策略性整合，强调创新组合以及寻找预测性生物标志物以优化患者选择和治疗效果。
