Physics·Technique·Biology
Carbon ion (12C6+) inhibits JAK2/STAT3 pathway and promotes CD8+ T cell infiltration in lung cancer
Wang Jiangtao, Dai Ziying, Miao Yandong, Zhao Ting, Zhao Da, Guan Quanlin, Li Qiang, Ran Juntao
Published 2022-09-15
Cite as Chin J Radiat Oncol, 2022, 31(9): 823-827. DOI: 10.3760/cma.j.cn113030-20210727-00273
Abstract
ObjectiveTo explore the alteration of JAK2/STAT3 pathway after carbon ion (12C6+) irradiation and the difference in the infiltration of CD8+ T cells in lung cancer regulated by downstream protein FOXP3.
MethodsSignificantly altered JAK2/STAT3 pathway and related differentially-expressed genes and proteins such as FOXP3 in lung cancer after carbon ion irradiation were screened based on RNA sequencing analysis in the Lewis tumor model of C57BL/6 mice. The correlation between FOXP3 and major immune cell infiltration in the immune microenvironment of lung cancer was analyzed using the ssGSEA immune infiltration algorithm in the R software "GSVA" and CD8+ T cell infiltration in the immune microenvironment of lung cancer was evaluated based on the carbon ion combined with STAT3 inhibition pathway (niclosamide).
ResultsThe JAK2/STAT3 pathway was inhibited and the expression of related genes and proteins was downregulated in lung cancer after carbon ion irradiation. Immune scoring based on the ssGSEA algorithm showed that FOXP3 expression was significantly negatively correlated with CD8+ T cell infiltration in the immune microenvironment of lung cancer. The role of targeting the JAK2/STAT3 pathway in increasing CD8+ T cell infiltration in lung cancer was further clarified by carbon ion irradiation combined with STAT3 inhibition (niclosamide).
ConclusionCarbon ion irradiation (12C6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.
Key words:
Carbon ions; Lung neoplasms; Tumor microenvironment; Immunity; JAK2/STAT3 pathway
Contributor Information
Wang Jiangtao
Department of Radiotherapy, First Hospital of Lanzhou University, Lanzhou 730000, China
The first Clinical Medical College of Lanzhou University, Lanzhou 730000, China
Dai Ziying
Department of Radiotherapy, First Hospital of Lanzhou University, Lanzhou 730000, China
Miao Yandong
The first Clinical Medical College of Lanzhou University, Lanzhou 730000, China
Zhao Ting
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
Zhao Da
Department of Oncology, First Hospital of Lanzhou University, Lanzhou 730000, China
Guan Quanlin
The first Clinical Medical College of Lanzhou University, Lanzhou 730000, China
Department of Surgical Oncology, First Hospital of Lanzhou University, Lanzhou 730000, China
Li Qiang
Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China
Ran Juntao
Department of Radiotherapy, First Hospital of Lanzhou University, Lanzhou 730000, China
The first Clinical Medical College of Lanzhou University, Lanzhou 730000, China
