Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang University, 1 Minde Road, Nanchang, 330006, China.
Departments of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100032, China.
J Hematol Oncol. 2023 Mar 21;16(1):28. doi: 10.1186/s13045-023-01426-4.
The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated secretory phenotype (SASP). On the one hand, the SASP promotes antitumor immunity, which enhances treatment efficacy; on the other hand, the SASP increases immunosuppressive cell infiltration, including myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), M2 macrophages, and N2 neutrophils, contributing to TIME suppression. Therefore, a deeper understanding of the regulation of the SASP and components contributing to robust antitumor immunity in elderly individuals with different cancer types and the available therapies is necessary to control tumor cell senescence and provide greater clinical benefits to patients. In this review, we summarize the key biological functions mediated by cytokines and intercellular interactions and significant components of the TME landscape, which influence the immunotherapy response in geriatric oncology. Furthermore, we summarize recent advances in clinical practices targeting TME components and discuss potential senescent TME targets.
肿瘤微环境（TME）已经得到了广泛的研究；然而，它非常复杂，目前仍不清楚，尤其是在老年患者中。衰老（senescence）是细胞对多种应激信号的反应，其特征是细胞周期稳定停滞和细胞形态及生理学的重大变化。据我们所知，衰老通过激活一组多效细胞因子、趋化因子、生长因子和蛋白酶，导致肿瘤细胞持续停滞并重塑肿瘤免疫微环境（TIME），从而构成衰老相关分泌表型（SASP）。一方面，SASP 促进抗肿瘤免疫，增强治疗效果；另一方面，SASP 增加了免疫抑制性细胞浸润，包括髓源性抑制细胞（MDSCs）、调节性 T 细胞（Tregs）、M2 巨噬细胞和 N2 中性粒细胞，导致 TIME 抑制。因此，需要更深入地了解 SASP 的调节以及不同癌症类型和现有治疗方法中与老年个体中强大抗肿瘤免疫相关的成分，以控制肿瘤细胞衰老并为患者提供更大的临床获益。在这篇综述中，我们总结了细胞因子和细胞间相互作用介导的关键生物学功能以及 TME 景观的重要组成部分，这些功能和组成部分影响老年肿瘤学中的免疫治疗反应。此外，我们总结了靶向 TME 成分的最新临床实践进展，并讨论了潜在的衰老 TME 靶点。
