Cueto Francisco J, Sancho David
Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
Cancers (Basel). 2021 Mar 26;13(7):1525. doi: 10.3390/cancers13071525.
Dendritic cells (DCs) prime anti-tumor T cell responses in tumor-draining lymph nodes and can restimulate T effector responses in the tumor site. Thus, in addition to unleashing T cell effector activity, current immunotherapies should be directed to boost DC function. Herein, we review the potential function of Flt3L as a tool for cancer immunotherapy. Flt3L is a growth factor that acts in Flt3-expressing multipotent progenitors and common lymphoid progenitors. Despite the broad expression of Flt3 in the hematopoietic progenitors, the main effect of the Flt3/Flt3L axis, revealed by the characterization of mice deficient in these genes, is the generation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs). However, Flt3 signaling through PI3K and mTOR may also affect the function of mature DCs. We recapitulate the use of Flt3L in preclinical studies either as a single agent or in combination with other cancer therapies. We also analyze the use of Flt3L in clinical trials. The strong correlation between type 1 cDC (cDC1) infiltration of human cancers with overall survival in many cancer types suggests the potential use of Flt3L to boost expansion of this DC subset. However, this may need the combination of Flt3L with other immunomodulatory agents to boost cancer immunotherapy.
树突状细胞（DCs）在肿瘤引流淋巴结中启动抗肿瘤T细胞反应，并可在肿瘤部位重新刺激T效应细胞反应。因此，除了释放T细胞效应活性外，当前的免疫疗法还应致力于增强DC功能。在此，我们综述了Flt3L作为癌症免疫治疗工具的潜在功能。Flt3L是一种生长因子，作用于表达Flt3的多能祖细胞和常见淋巴祖细胞。尽管Flt3在造血祖细胞中广泛表达，但通过对这些基因缺陷小鼠的特征分析发现，Flt3/Flt3L轴的主要作用是产生常规DCs（cDCs）和浆细胞样DCs（pDCs）。然而，通过PI3K和mTOR的Flt3信号传导也可能影响成熟DCs的功能。我们总结了Flt3L在临床前研究中作为单一药物或与其他癌症治疗联合使用的情况。我们还分析了Flt3L在临床试验中的应用。在许多癌症类型中，人类癌症的1型cDC（cDC1）浸润与总生存期之间的强相关性表明，Flt3L可能有潜力促进该DC亚群的扩增。然而，这可能需要将Flt3L与其他免疫调节药物联合使用，以增强癌症免疫治疗效果。
