Carbon ion (12C6+) inhibits JAK2/STAT3 pathway and promotes CD8+ T cell infiltration in lung cancer
Wang Jiangtao1,2, Dai Ziying1, Miao Yandong2, Zhao Ting3, Zhao Da4, Guan Quanlin2,5, Li Qiang3, Ran Juntao1,2
1Department of Radiotherapy, First Hospital of Lanzhou University, Lanzhou 730000, China; 2The first Clinical Medical College of Lanzhou University, Lanzhou 730000, China; 3Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China; 4Department of Oncology, First Hospital of Lanzhou University, Lanzhou 730000, China; 5Department of Surgical Oncology, First Hospital of Lanzhou University, Lanzhou 730000, China
Abstract：Objective To 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. Methods Significantly 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). Results The 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). Conclusion Carbon ion irradiation (12C6+) can play a synergistic role with immunotherapy by targeting the JAK2/STAT3 pathway.
Wang Jiangtao,Dai Ziying,Miao Yandong et al. Carbon ion (12C6+) inhibits JAK2/STAT3 pathway and promotes CD8+ T cell infiltration in lung cancer[J]. Chinese Journal of Radiation Oncology, 2022, 31(9): 823-827.
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