Department of Medicine, University of Texas Health San Antonio, TX 78229, USA.
Department of Urology, University of Texas Health San Antonio, TX 78229, USA; The UT Health Cancer Center, University of Texas Health San Antonio, TX 78229, USA.
Exp Gerontol. 2018 Jul 1;107:27-36. doi: 10.1016/j.exger.2017.10.002. Epub 2017 Oct 4.
Improvements in understanding cancer immunopathogenesis have now led to unprecedented successes in immunotherapy to treat numerous cancers. Although aging is the most important risk factor for cancer, most pre-clinical cancer immunotherapy studies are undertaken in young hosts. This review covers age-related immune changes as they affect cancer immune surveillance, immunopathogenesis and immune therapy responses. Declining T cell function with age can impede efficacy of age-related cancer immunotherapies, but examples of successful approaches to breach this barrier have been reported. It is further recognized now that immune functions with age do not simply decline, but that they change in potentially detrimental ways. For example, detrimental immune cell populations can become predominant during aging (notably pro-inflammatory cells), the prevalence or function of suppressive cells can increase (notably myeloid derived suppressor cells), drugs can have age-specific effects on immune cells, and attributes of the aged microenvironment can impede or subvert immunity. Key advances in these and related areas will be reviewed as they pertain to cancer immunotherapy in the aged, and areas requiring additional study and some speculations on future research directions will be addressed. We prefer the term Age Related Immune Dysfunction (ARID) as most encompassing the totality of age-associated immune changes.
对癌症免疫发病机制的理解的提高，现在已经导致免疫疗法在治疗众多癌症方面取得了前所未有的成功。尽管衰老是癌症的最重要危险因素，但大多数临床前癌症免疫治疗研究都是在年轻宿主中进行的。这篇综述涵盖了与年龄相关的免疫变化，因为它们会影响癌症的免疫监视、免疫发病机制和免疫治疗反应。随着年龄的增长，T 细胞功能的下降会影响与年龄相关的癌症免疫疗法的疗效，但已经有报道成功地克服了这一障碍的方法。现在人们进一步认识到，随着年龄的增长，免疫功能并非简单地下降，而是以潜在有害的方式发生变化。例如，有害的免疫细胞群在衰老过程中可能变得占主导地位（特别是促炎细胞），抑制性细胞的流行或功能可能增加（特别是髓源性抑制细胞），药物对免疫细胞具有年龄特异性的影响，以及衰老微环境的特征可能会阻碍或破坏免疫。将重点讨论这些和相关领域的关键进展，因为它们与老年癌症免疫疗法有关，并将讨论需要进一步研究的领域以及对未来研究方向的一些推测。我们更喜欢使用“与年龄相关的免疫功能障碍（ARID）”一词，因为它最全面地涵盖了与年龄相关的免疫变化的全部内容。
