Effects of Klebsiella pneumoniae on lung cancer progression and potential mechanisms
JING Lin
YU Xiran
WANG Dan
CHEN Zhinan
JIANG Jianli
Abstract：Objective To clarify the impact of intratumoral Klebsiella pneumoniae(KP)on lung cancer progression and preliminarily explore the underlying mechanisms.Methods C57BL/6J mice were used to construct Lewis lung carcinoma subcutaneous tumor model and KP was colonized in the tumor tissues by intratumoral injection.Mice were randomly assigned to the control group(Vehicle group,n=8;intratumoral injection of phosphate-buffered saline)and the experimental group(KP group,n=8).The colonization effect was validated by qRT-PCR and FISH,and the impact of KP on tumor growth was observed.After the animal experiments,tumor tissues were collected for further analysis.Flow cytometry and immunofluorescence staining were employed to detect the quantity and function of different immune cell subsets in the tumor tissues.Additionally,RNA-seq,qRT-PCR,and ELISA were performed to detect changes in gene or protein expression levels in the tumor tissues.Results Compared with the Vehicle group,the volume of the subcutaneous tumor was larger(P＜0.01)and the tumor mass was higher in the KP group(P＜0.05).Compared with the Vehicle group,the KP group had decreased proportions of CD8+T cells(P＜0.05),Perforin+CD8+T cells(P＜0.05),and CD4+T cells(P＜0.01)in tumor tissues.Besides,the proportion of polymorphonuclear myeloid-derived suppressor cells was increased in tumor tissues of the KP group(P＜0.01),while no significant changes were observed in the proportion of macrophages and monocytic myeloid-derived suppressor cells.Compared with the Vehicle group,the upregulation of CD274,ARG2,ARG1,NOS2,IL-6,IL-1β,CXCL2,and CXCL5 gene expression could be observed in tumor tissues of the KP group(P＜0.05).Compared with the Vehicle group,the IL-1β concentration was higher in tumor tissues of the KP group(P＜0.05).Conclusion By recruiting myeloid-derived suppressor cells to inhibit the number and function of CD8+T cells,intratumoral KP reshapes the immune microenvironment to accelerate lung cancer progression.
Keywords：lung neoplasmsKlebsiella pneumoniaetumor microenvironmentmyeloid-derived suppressor cellsCD8+T lymphocytesneoplasm progressionimmune toleranceC57BL mice
Publication Date：2025-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 906-912 )