The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy.
The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy.
复制标题
DOI：
10.3390/cancers13071525
复制
发表时间：
2021-03-26
期刊：
影响因子：
5.2
通讯作者：
Sancho D
中科院分区：
文献类型：
--
作者：
Cueto FJ;Sancho D
癌症免疫治疗目前主要集中在增强T细胞的效应功能上。然而，需要树突状细胞（DC）来引发T细胞，这表明DC可以是免疫治疗的有吸引力的靶点。Flt 3L/Flt 3是DC发育和功能的重要途径，尽管其在癌症免疫治疗中的潜力尚未明确。在此，我们将回顾目前的证据表明，通过Flt 3/Flt 3L轴刺激DC可能有助于改善癌症免疫治疗。树突状细胞（DC）在肿瘤引流淋巴结中引发抗肿瘤T细胞应答，并且可以再刺激肿瘤部位中的T效应子应答。因此，除了释放T细胞效应子活性之外，当前的免疫疗法应该针对增强DC功能。本文就Flt 3L作为肿瘤免疫治疗工具的潜在功能进行综述。Flt 3L是在表达Flt 3的多能祖细胞和普通淋巴祖细胞中起作用的生长因子。尽管Flt 3在造血祖细胞中广泛表达，但通过表征这些基因缺陷的小鼠所揭示的Flt 3/Flt 3L轴的主要作用是产生常规DC（cDC）和浆细胞样DC（pDC）。然而，Flt 3信号通过PI 3 K和mTOR也可能影响成熟DC的功能。我们概括了Flt 3L在临床前研究中作为单一药物或与其他癌症疗法联合使用的情况。我们还分析了Flt 3L在临床试验中的使用。人类癌症的1型cDC（cDC 1）浸润与许多癌症类型中的总存活率之间的强相关性表明Flt 3L促进该DC亚群的扩增的潜在用途。然而，这可能需要Flt 3L与其他免疫调节剂的组合来加强癌症免疫治疗。
Cancer immunotherapy is currently focused mainly on the enhancement of the effector function of T cells. However, dendritic cells (DCs) are needed to prime T cells, suggesting that DCs can be an attractive target for immunotherapy. Flt3L/Flt3 is an essential pathway for DC development and function, although its potential in cancer immunotherapy is not yet clearly established. Herein, we will review the current evidence which suggests that the stimulation of DCs through the Flt3/Flt3L axis may contribute to improved cancer immunotherapy. 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.
登录
查看更多内容
DOI：
10.1084/jem.20141441
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Breton G;Lee J;Zhou YJ;Schreiber JJ;Keler T;Puhr S;Anandasabapathy N;Schlesinger S;Caskey M;Liu K;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
64.5
作者：
Binnewies, Mikhail;Mujal, Adriana M.;Krummel, Matthew F.
通讯作者：
Krummel, Matthew F.
增强的抗肿瘤免疫力需要常驻记忆CD8+T细胞和循环记忆CD8+T细胞之间的相互作用。
影响因子：
16.6
作者：
Enamorado M;Iborra S;Priego E;Cueto FJ;Quintana JA;Martínez-Cano S;Mejías-Pérez E;Esteban M;Melero I;Hidalgo A;Sancho D
通讯作者：
Sancho D
影响因子：
18.4
作者：
Böttcher JP;Reis e Sousa C
通讯作者：
Reis e Sousa C
影响因子：
5.3
作者：
DOSIL, M;WANG, SL;LEMISCHKA, IR
通讯作者：
LEMISCHKA, IR