Wang Leihan, Tang Dong
Clinical Medical College, Yangzhou University, Yangzhou, People's Republic of China.
Department of General Surgery, Institute of General Surgery, Northern Jiangsu People's Hospital Affiliated to Yangzhou University; Northern Jiangsu People's Hospital; The Yangzhou Clinical Medical College of Xuzhou Medical University; The Yangzhou School of Clinical Medicine of Dalian Medical University; The Yangzhou School of Clinical Medicine of Nanjing Medical University; Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, 225000, China.
Cell Commun Signal. 2025 Mar 10;23(1):128. doi: 10.1186/s12964-025-02082-6.
The body's innate immune system plays a pivotal role in identifying and eliminating cancer cells. However, as the immune system ages, its functionality can deteriorate, becoming dysfunctional, inefficient, or even inactive-a condition referred to as immunosenescence. This decline significantly increases the risk of malignancies. While the pro-cancer effects of T-cell aging have been widely explored, there remains a notable gap in the literature regarding the impact of aging on innate immune cells, such as macrophages and neutrophils. This review seeks to address this gap, with emphasis on these cell types. Furthermore, although certain cancer immunotherapies, including immune checkpoint inhibitors (ICIs), have demonstrated efficacy across a broad spectrum of cancers, elderly patients are less likely to derive clinical benefit from these treatments. In some cases, they may even experience immune-related adverse events (irAEs). While senolytic strategies have shown promise in exerting anti-cancer effects, their adverse reactions and potential off-target effects present significant challenges. This review aims to elucidate the pro-cancer effects of immunosenescence, its implications for the efficacy and safety of ICIs, and potential anti-aging treatment strategies. In addition, optimizing anti-aging therapies to minimize adverse reactions and enhance therapeutic outcomes remains a critical focus for future research endeavors.
人体的固有免疫系统在识别和清除癌细胞方面发挥着关键作用。然而，随着免疫系统的老化，其功能可能会恶化，变得功能失调、效率低下甚至不活跃——这种情况被称为免疫衰老。这种衰退显著增加了患恶性肿瘤的风险。虽然T细胞衰老的促癌作用已得到广泛研究，但关于衰老对巨噬细胞和中性粒细胞等固有免疫细胞的影响，文献中仍存在明显空白。本综述旨在填补这一空白，重点关注这些细胞类型。此外，尽管某些癌症免疫疗法，包括免疫检查点抑制剂（ICIs），已在多种癌症中显示出疗效，但老年患者从这些治疗中获得临床益处的可能性较小。在某些情况下，他们甚至可能会经历免疫相关的不良事件（irAEs）。虽然衰老细胞溶解策略在发挥抗癌作用方面显示出前景，但其不良反应和潜在的脱靶效应带来了重大挑战。本综述旨在阐明免疫衰老的促癌作用、其对ICIs疗效和安全性的影响以及潜在的抗衰老治疗策略。此外，优化抗衰老疗法以尽量减少不良反应并提高治疗效果仍然是未来研究努力的关键重点。
