De Padova Silvia, Urbini Milena, Schepisi Giuseppe, Virga Alessandra, Meggiolaro Elena, Rossi Lorena, Fabbri Francesco, Bertelli Tatiana, Ulivi Paola, Ruffilli Federica, Casadei Chiara, Gurioli Giorgia, Rosti Giovanni, Grassi Luigi, De Giorgi Ugo
Psycho-Oncology Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Front Oncol. 2021 Jan 15;10:564346. doi: 10.3389/fonc.2020.564346. eCollection 2020.
Testicular cancer (TC) is the most frequent solid tumor diagnosed in young adult males. Although it is a curable tumor, it is frequently associated with considerable short-term and long-term morbidity. Both biological and psychological stress experienced during cancer therapy may be responsible for stimulating molecular processes that induce premature aging and deterioration of immune system (immunosenescence) in TC survivors, leading to an increased susceptibility to infections, cancer, and autoimmune diseases. Immunosenescence is a remodeling of immune cell populations with inversion of the CD4:CD8 ratio, accumulation of highly differentiated memory cells, shrinkage of telomeres, shift of T-cell response to Th2 type, and release of pro-inflammatory signals. TC survivors exposed to chemotherapy show features of immunological aging, including an increase in memory T-cells (CD4+ and CD8+) and high expression of the senescence biomarker p16INK4a in CD3+ lymphocytes. However, the plethora of factors involved in the premature aging of TC survivors make the situation more complex if we also take into account the psychological stress and hormonal changes experienced by patients, as well as the high-dose chemotherapy and hematopoietic stem cell transplantation that some individuals may be required to undergo. The relatively young age and the long life expectancy of TC patients bear witness to the importance of improving quality of life and of alleviating long-term side-effects of cancer treatments. Within this context, the present review takes an in-depth look at the molecular mechanisms of immunosenescence, describing experimental evidence of cancer survivor aging and highlighting the interconnected relationship between the many factors modulating the aging of the immune system of TC survivors.
睾丸癌（TC）是年轻成年男性中最常见的实体瘤。尽管它是一种可治愈的肿瘤，但它常常伴随着相当程度的短期和长期发病率。癌症治疗期间经历的生物和心理压力都可能刺激分子过程，从而导致TC幸存者过早衰老和免疫系统恶化（免疫衰老），进而增加对感染、癌症和自身免疫性疾病的易感性。免疫衰老是免疫细胞群体的重塑，表现为CD4:CD8比值倒置、高度分化的记忆细胞积累、端粒缩短、T细胞反应向Th2型转变以及促炎信号的释放。接受化疗的TC幸存者表现出免疫衰老的特征，包括记忆T细胞（CD4+和CD8+）增加以及CD3+淋巴细胞中衰老生物标志物p16INK4a的高表达。然而，如果我们还考虑到患者经历的心理压力和激素变化，以及一些个体可能需要接受的高剂量化疗和造血干细胞移植，那么涉及TC幸存者过早衰老的众多因素会使情况变得更加复杂。TC患者相对年轻的年龄和较长的预期寿命证明了改善生活质量和减轻癌症治疗长期副作用的重要性。在此背景下，本综述深入探讨了免疫衰老的分子机制，描述了癌症幸存者衰老的实验证据，并强调了调节TC幸存者免疫系统衰老的众多因素之间的相互关系。
