Open Access

ARTICLE

CD103⁺ Cell Growth Factor Flt3L Enhances the Efficacy of Immune Checkpoint Blockades in Murine Glioblastoma Model

Xiaolin Miao^*1, Yiqi Chen^*1, Ke Hao^†1, Meiqin Zheng^‡, Bingyu Chen^†, Kaiqiang Li^†, Ying Wang^†, Wei Zhang^§, Yu Zhang^§, Xiaozhou Mou^§, Shanshan Jiang^¶, Zhen Wang^‡§

* Eye Hospital of Wenzhou Medical University, Zhejiang, P.R. China
† Research Center of Blood Transfusion Medicine, Education Ministry Key Laboratory of Laboratory Medicine, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
‡ School of Laboratory Medicine and Life Science, Wenzhou Medical University, Zhejiang, P.R. China
§ Clinical Research Institute, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
¶ Department of Gynecology, Zhejiang Provincial People’s Hospital, Zhejiang, P.R. China
1 These authors provided equal contribution to this work.

Oncology Research 2018, 26(2), 173-182. https://doi.org/10.3727/096504017X14841698396865

Abstract

Glioblastoma is a lethal disease featuring a high proliferation of tumor cells, excessive angiogenesis, and heavy drug resistance. The overall survival of glioblastoma patients has been dismal, even with an intensive standard of care. Recent advances in immune checkpoint blockades are changing the treatment of cancers. However, the efficacy of immune checkpoint blockades in glioblastoma is still unclear. Here we investigated the roles of CD103⁺ cells in regulating the effect of immune checkpoint blockades in glioblastoma mouse models. Our findings indicated that the murine glioblastoma model was not sensitive to immune checkpoint blockades. Flt3L, a growth factor for CD103⁺ cells, could significantly increase the number of CD103⁺ dendritic cells in the murine glioblastoma model and, thus, sensitize murine glioblastoma to immune checkpoint blockades. Downstream analysis indicated that the Flt3L and immune checkpoint blockade combination increased the number of tumor-infiltrating CD8⁺ cells, decreased immune checkpoint expression, and therefore enhanced the antitumor immune response in the murine glioblastoma model. These findings suggested that Flt3L could enhance the efficacy of immune checkpoint blockades in glioblastoma via expanding CD103⁺ dendritic cells and downstream antitumor immune response.

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