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Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis.

ABSTRACT: It is still a big puzzle how ovarian cancer cells and the tumor microenvironment (TME) attract lymphocytes infiltration for facilitating metastasis, a leading cause of death from gynecological malignancies. Using genome-wide LncRNA microarray assay, here we report that a LncRNA associated with ovarian cancer metastasis (LncOVM) is highly correlated with poor prognosis and survival. LncOVM interacts with and stabilizes PPIP5K2 by suppressing ubiquitinated degradation to promote complement C5 secretion from ovarian cancer cells. The TME-enriched complement C5 attracts myeloid-derived suppressor cells (MDSCs) infiltration in TME to facilitate metastasis. Knockdown of LncOVM or PPIP5K2 inhibits tumor progression in xenograft models. Application of C5aR antibody or inhibitor (CCX168) inhibits MDSC recruitment and restores the suppression of tumorigenesis and metastasis in vivo. Our study reveals that suppression of ovarian cancer metastasis can be achieved by targeting MDSC infiltration in TME through disrupting LncOVM-PPIP5K2-complement axis, providing an option for treating ovarian cancer patients.

SUBMITTER: Li Y

PROVIDER: S-EPMC9254473 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis.

Li Yichen Y Zhang Qian Q Wu Mandi M Zhang Peidong P Huang Liang L Ai Xiaolin X Yang Zhengnan Z Shen Qiuhong Q Wang Yiran Y Wang Ping P Zhou Shengtao S He Ming-Liang ML

International journal of biological sciences 20220521 9

It is still a big puzzle how ovarian cancer cells and the tumor microenvironment (TME) attract lymphocytes infiltration for facilitating metastasis, a leading cause of death from gynecological malignancies. Using genome-wide LncRNA microarray assay, here we report that a LncRNA associated with ovarian cancer metastasis (LncOVM) is highly correlated with poor prognosis and survival. LncOVM interacts with and stabilizes PPIP5K2 by suppressing ubiquitinated degradation to promote complement C5 secr ...[more]

PMID: 35813475

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Project description:Objective: Because of the modest immunotherapeutic response among ovarian carcinoma (OC) patients, it is significant to evaluate antitumor immune response and develop more effective precision immunotherapeutic regimens. Here, this study aimed to determine diverse immune subtypes of OC. Methods: This study curated the expression profiles of prognostic immunologically relevant genes and conducted consensus clustering analyses for determining immune subtypes among OC patients in TCGA cohort. With Boruta algorithm, characteristic genes were screened for conducting an immune scoring system through principal component analysis algorithm. The single-sample gene set enrichment analysis and ESTIAMTE methods were adopted for quantifying the immune infiltrates and responses to chemotherapeutic agents were estimated with pRRophetic algorithm. Two immunotherapeutic cohorts were used for investigating the efficacy of immune score in predicting therapeutic benefits. Results: Two immune subtypes were conducted among 377 OC patients. Immune subtype 2 was characterized by worse clinical prognosis, more frequent genetic variations and mutations, enhanced immune infiltrates, and increased expression of MHC molecules and programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1). In total, 30 prognosis-relevant characteristic immune subtype-derived genes were identified for constructing the immune score of OC patients. High immune score was linked with more dismal prognosis, decreased immune infiltrations, and expression of MHC molecules. High immune score presented favorable sensitivity to doxorubicin and vinorelbine and reduced sensitivity to cisplatin. In addition, immune score possessed the potential in predicting benefits from anti-PD-1/PD-L1 therapy. Conclusion: Collectively, our findings propose two complex and diverse immune subtypes of OC. Quantitative assessment of immune subtypes in individual patients strengthens the understanding of tumor microenvironment features and promotes more effective immunotherapeutic regimens.

Dataset Information

Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis.

Publications

Suppressing MDSC Infiltration in Tumor Microenvironment Serves as an Option for Treating Ovarian Cancer Metastasis.

Similar Datasets

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