Radiation therapy enhanced therapeutic efficacy of anti-PD1 against gastric cancer

Autor: Zhenkun Yan, Haiyao Yu, Sen Hong, Helei Wang, Miaomiao Bi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Health
Toxicology and Mutagenesis
medicine.medical_treatment
T-Lymphocytes
Programmed Cell Death 1 Receptor
immunotherapy
intratumor T cells
Lymphocyte Activation
radiation therapy
Chemokine CXCL9
Mice
0302 clinical medicine
Regular Paper
Tumor Microenvironment
0303 health sciences
Radiation
biology
medicine.diagnostic_test
Chemistry
Immunohistochemistry
030220 oncology & carcinogenesis
Tumor necrosis factor alpha
Female
Immunotherapy
Antibody
Signal Transduction
Real-Time Polymerase Chain Reaction
Flow cytometry
03 medical and health sciences
Stomach Neoplasms
Cell Line
Tumor
medicine
Animals
Radiology
Nuclear Medicine and imaging
anti-PD1
Clonogenic assay
030304 developmental biology
Cell Proliferation
Tumor microenvironment
Radiotherapy
Tumor Necrosis Factor-alpha
gastric cancer
Cancer
Dose-Response Relationship
Radiation
Dendritic Cells
Interferon-beta
medicine.disease
Radiation therapy
Immune System
Cancer research
biology.protein
AcademicSubjects/SCI00960
AcademicSubjects/MED00870
Zdroj: Journal of Radiation Research
ISSN: 1349-9157
0449-3060
Popis: Radiation therapy is an important method in tumor treatment with distinct responses. This study aimed to investigate the immune effects of radiation therapy on the syngeneic gastric tumor model. Mouse forestomach carcinoma (MFC) cells were irradiated with different X-ray doses. Cell proliferation was determined by clonogenic assay. Gene and protein expression were determined by real-time quantitative PCR and western blot, respectively. The tumor model was established by subcutaneously injecting tumor cells in 615-(H-2 K) mice. Levels of immune-related factors in tumor tissues were determined by immunohistochemistry and flow cytometry. 5 Gy × 3 (three subfractions with 4 h interval) treatment significantly inhibited cell proliferation. Protein expression of stimulator of interferon genes (Sting) and gene expression of IFNB1, TNFα as well as CXCL-9 significantly increased in MFC cells after irradiation. In the MFC mouse model, no obvious tumor regression was observed after irradiation treatment. Further studies showed Sting protein expression, infiltration of dendritic cells and T cells, and significantly increased PD-1/PD-L1 expression in tumor tissues. Moreover, the irradiation treatment activated T cells and enhanced the therapeutic effects of anti-PD1 antibody against MFC tumor. Our data demonstrated that although the MFC tumor was not sensitive to radiation therapy, the tumor microenvironment could be primed after irradiation. Radiation therapy combined with immunotherapy can greatly improve anti-tumor activities in radiation therapy-insensitive tumor models.
Databáze: OpenAIRE
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