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

Autor: Bingyu Chen, Shanshan Jiang, Ke Hao, Wei Zhang, Yiqi Chen, Yu Zhang, Xiaozhou Mou, Wang Zhen, Xiaolin Miao, Li Kaiqiang, Ying Wang, Mei-Qin Zheng
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Cancer Research
Angiogenesis
medicine.medical_treatment
chemical and pharmacologic phenomena
CD8-Positive T-Lymphocytes
Article
Mouse model
Immunomodulation
03 medical and health sciences
Mice
Immune system
Antineoplastic Agents
Immunological
Lymphocytes
Tumor-Infiltrating
Antigen
Antigens
CD
Cell Line
Tumor
medicine
Biomarkers
Tumor
Animals
Humans
Molecular Targeted Therapy
neoplasms
Cell growth
business.industry
Growth factor
Flt3L
Membrane Proteins
General Medicine
Dendritic Cells
biochemical phenomena
metabolism
and nutrition
Xenograft Model Antitumor Assays
Immune checkpoint
Blockade
nervous system diseases
Disease Models
Animal
030104 developmental biology
Oncology
Immunology
Cancer research
Immune checkpoints
CD103
bacteria
business
Glioblastoma
Integrin alpha Chains
CD8
Biomarkers
Zdroj: Oncology Research
ISSN: 1555-3906
0965-0407
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: