Carbon ion radiotherapy boosts anti-tumour immune responses by inhibiting myeloid-derived suppressor cells in melanoma-bearing mice.
Heng ZhouPengfei YangHaining LiLiying ZhangJin LiTianyi ZhangChengyan ShengJufang WangPublished in: Cell death discovery (2021)
Numerous studies have shown that carbon ion radiotherapy (CIRT) induces anti-cancer immune responses in melanoma patients, yet the mechanism remains elusive. The abundance of myeloid-derived suppressor cells (MDSC) in the tumour microenvironment is associated with therapeutic efficacy and disease outcome. This study analysed the changes in the immune contexture in response to the carbon ion treatment. The murine melanoma B16, MelanA, and S91 tumour models were established in syngeneic immunocompetent mice. Then, the tumours were irradiated with carbon ion beams, and flow cytometry was utilised to observe the immune contexture changes in the bone marrow, peripheral blood, spleen, and tumours. The immune infiltrates in the tumour tissues were further assessed using haematoxylin/eosin staining and immunohistochemistry. The immunoblot detected the expression of proteins associated with the JAK/STAT signalling pathway. The secretion of immune-related cytokines was examined using ELISA. Compared to conventional radiotherapy, particle beams have distinct advantages in cancer therapy. Here, the use of carbon ion beams (5 GyE) for melanoma-bearing mice was found to reduce the population of MDSC in the bone marrow, peripheral blood, and spleen of the animals via a JAK2/STAT3-dependent mechanism. The percentage of CD3+, CD4+, CD8+ T cells, macrophages, and natural killer cells increased after radiation, resulting in reduced tumour growth and prolonged overall survival in the three different mouse models of melanoma. This study, therefore, substantiated that CIRT boosts anti-tumour immune responses via the inhibition of MDSC.
Keyphrases
- immune response
- peripheral blood
- bone marrow
- flow cytometry
- early stage
- induced apoptosis
- cancer therapy
- high fat diet induced
- radiation induced
- locally advanced
- end stage renal disease
- cell cycle arrest
- radiation therapy
- mesenchymal stem cells
- mouse model
- toll like receptor
- dendritic cells
- newly diagnosed
- natural killer cells
- type diabetes
- signaling pathway
- chronic kidney disease
- gene expression
- poor prognosis
- drug delivery
- basal cell carcinoma
- peritoneal dialysis
- adipose tissue
- cell proliferation
- metabolic syndrome
- patient reported outcomes
- inflammatory response
- oxidative stress
- microbial community
- long non coding rna
- combination therapy