Targeting senescence-associated secretory phenotypes to remodel the tumour microenvironment and modulate tumour outcomes

IF 7.9 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Clinical and Translational Medicine Pub Date : 2024-09-13 DOI:10.1002/ctm2.1772

Jiaqiang Xiong, Lu Dong, Qiongying Lv, Yutong Yin, Jiahui Zhao, Youning Ke, Shixuan Wang, Wei Zhang, Meng Wu

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Abstract

Tumour cell senescence can be induced by various factors, including DNA damage, inflammatory signals, genetic toxins, ionising radiation and nutrient metabolism. The senescence-associated secretory phenotype (SASP), secreted by senescent tumour cells, possesses the capacity to modulate various immune cells, including macrophages, T cells, natural killer cells and myeloid-derived suppressor cells, as well as vascular endothelial cells and fibroblasts within the tumour microenvironment (TME), and this modulation can result in either the promotion or suppression of tumorigenesis and progression. Exploring the impact of SASP on the TME could identify potential therapeutic targets, yet limited studies have dissected its functions. In this review, we delve into the causes and mechanisms of tumour cell senescence. We then concentrate on the influence of SASP on the tumour immune microenvironment, angiogenesis, extracellular matrix and the reprogramming of cancer stem cells, along with their associated tumour outcomes. Last, we present a comprehensive overview of the diverse array of senotherapeutics, highlighting their prospective advantages and challenge for the treatment of cancer patients.

Key points

Senescence-associated secretory phenotype (SASP) secretion from senescent tumour cells significantly impacts cancer progression and biology.
SASP is involved in regulating the remodelling of the tumour microenvironment, including immune microenvironment, vascular, extracellular matrix and cancer stem cells.
Senotherapeutics, such as senolytic, senomorphic, nanotherapy and senolytic vaccines, hold promise for enhancing cancer treatment efficacy.

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以衰老相关分泌表型为靶点，重塑肿瘤微环境并调节肿瘤结局

肿瘤细胞衰老可由多种因素诱发，包括 DNA 损伤、炎症信号、遗传毒素、电离辐射和营养代谢。衰老肿瘤细胞分泌的衰老相关分泌表型（SASP）有能力调节各种免疫细胞，包括巨噬细胞、T细胞、自然杀伤细胞和髓源性抑制细胞，以及肿瘤微环境（TME）中的血管内皮细胞和成纤维细胞，这种调节可以促进或抑制肿瘤的发生和发展。探索 SASP 对肿瘤微环境的影响可以确定潜在的治疗靶点，但对其功能的研究还很有限。在本综述中，我们将深入探讨肿瘤细胞衰老的原因和机制。然后，我们集中讨论 SASP 对肿瘤免疫微环境、血管生成、细胞外基质和癌症干细胞重编程的影响，以及与之相关的肿瘤结局。最后，我们全面概述了各种衰老治疗药物，强调了它们在治疗癌症患者方面的优势和挑战。要点衰老肿瘤细胞分泌的衰老相关分泌表型（SASP）对癌症的进展和生物学有重大影响。 SASP 参与调节肿瘤微环境的重塑，包括免疫微环境、血管、细胞外基质和癌症干细胞。衰老疗法，如衰老溶解疗法、衰老形态疗法、纳米疗法和衰老溶解疫苗，有望提高癌症治疗效果。

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来源期刊

Clinical and Translational Medicine Multiple-

CiteScore

15.90

自引率

1.90%

发文量

450

审稿时长

4 weeks

期刊介绍： Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.