Kähkönen Tiina E, Halleen Jussi M, Bernoulli Jenni
OncoBone Ltd., Kalimenojankuja 3 C 4, FI-90810 Kiviniemi, Finland.
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FI-20520 Turku, Finland.
Cancers (Basel). 2020 Jun 18;12(6):1615. doi: 10.3390/cancers12061615.
Metastases cause high mortality in several cancers and immunotherapies are expected to be effective in the prevention and treatment of metastatic disease. However, only a minority of patients benefit from immunotherapies. This creates a need for novel therapies that are efficacious regardless of the cancer types and metastatic environments they are growing in. Preclinical immuno-oncology models for studying metastases have long been limited to syngeneic or carcinogenesis-inducible models that have murine cancer and immune cells. However, the translational power of these models has been questioned. Interactions between tumor and immune cells are often species-specific and regulated by different cytokines in mice and humans. For increased translational power, mice engrafted with functional parts of human immune system have been developed. These humanized mice are utilized to advance understanding the role of immune cells in the metastatic process, but increasingly also to study the efficacy and safety of novel immunotherapies. From these aspects, this review will discuss the role of immune cells in the metastatic process and the utility of humanized mouse models in immuno-oncology research for metastatic cancers, covering several models from the perspective of efficacy and safety of immunotherapies.
转移在多种癌症中导致高死亡率，免疫疗法有望有效预防和治疗转移性疾病。然而，只有少数患者能从免疫疗法中获益。这就需要开发新型疗法，无论癌症类型及其生长的转移环境如何，都能有效发挥作用。长期以来，用于研究转移的临床前免疫肿瘤学模型仅限于具有小鼠癌症和免疫细胞的同基因或致癌诱导模型。然而，这些模型的转化能力受到了质疑。肿瘤与免疫细胞之间的相互作用通常具有物种特异性，并且在小鼠和人类中受不同细胞因子的调节。为了提高转化能力，已开发出植入人类免疫系统功能部分的小鼠。这些人源化小鼠被用于增进对免疫细胞在转移过程中作用的理解，但越来越多地也用于研究新型免疫疗法的疗效和安全性。从这些方面来看，本综述将讨论免疫细胞在转移过程中的作用以及人源化小鼠模型在转移性癌症免疫肿瘤学研究中的应用，从免疫疗法的疗效和安全性角度涵盖多种模型。
