Division of Gynecologic Oncology, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
Leuven Cancer Institute (LKI), 3000 Leuven, Belgium.
Int J Mol Sci. 2019 Jul 23;20(14):3586. doi: 10.3390/ijms20143586.
Cancer immunotherapy has entered the forefront of cancer treatment, but major challenges still exist, such as the limited proportion of patients that respond to treatment and treatment-related toxicity. Therefore, biomarkers to predict which patients will benefit from therapy without major side effects are of the utmost importance. Moreover, novel therapeutic targets to increase the proportion of responding patients on a given immunotherapy or to alleviate immunotherapy-induced toxicity could be a valuable adjunct to immunotherapy treatment. Host factors such as age, obesity, and the composition of the gut microbiome have considerable effects on immune responses and, hence, could have a large impact on the outcome of immunotherapies. Moreover, since these host factors differ considerably between preclinical mouse models and human cancer patients, it might be possible that these host factors account, in part, for the observed discrepancies in outcomes between mice experiments and clinical trials. In this review, we discuss the latest data on the influence of aging, obesity, and the gut microbiome on the anti-tumor immune response and immunotherapy and propose avenues to increase our knowledge on this topic in order to improve patient selection for cancer immunotherapy treatment.
癌症免疫疗法已成为癌症治疗的前沿领域，但仍存在重大挑战，例如接受治疗的患者比例有限，以及与治疗相关的毒性。因此，预测哪些患者将受益于无重大副作用的治疗而无重大副作用的生物标志物至关重要。此外，增加特定免疫疗法反应患者比例或减轻免疫疗法诱导毒性的新型治疗靶点可能是免疫疗法治疗的有益辅助手段。宿主因素，如年龄、肥胖和肠道微生物组的组成，对免疫反应有很大影响，因此可能对免疫疗法的结果有很大影响。此外，由于这些宿主因素在临床前小鼠模型和人类癌症患者之间存在很大差异，因此这些宿主因素可能部分解释了在小鼠实验和临床试验之间观察到的结果差异。在这篇综述中，我们讨论了衰老、肥胖和肠道微生物组对抗肿瘤免疫反应和免疫疗法的最新影响数据，并提出了增加这一主题知识的途径，以改善癌症免疫疗法治疗的患者选择。
