Lnc-17Rik promotes the immunosuppressive function of Myeloid-Derived suppressive cells in esophageal cancer

Wen, Jiexia; Xuan, Bin; Gao, Yuan; Liu, Yang; Wang, Liwei; Li, He; Meng, Xiangying; Zhou, Tao; Yang, Tao; Guo, Kening; Wang, Yimin

doi:10.1016/j.cellimm.2023.104676

Cited by 6 publications

(3 citation statements)

References 60 publications

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“…Recently, COX2 has become the hotspot in anti-cancer research, and it has been demonstrated that COX2 could play an important role in tumor promotion and the sensitivity of immunotherapy [27][28][29]. High expression of COX2 can promote the proliferation, angiogenesis, invasiveness, metastasis, and also the inhibition of apoptosis and immuno-surveillance [27,30].…”

Section: Discussionmentioning

confidence: 99%

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up

Jiang,

Tian,

Guo

et al. 2024

Cancer Cell Int

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Objective This study aimed to construct a model based on 23 enrolled molecules to evaluate prognoses of pT2/3N0M0 esophageal squamous cell carcinoma (ESCC) patients with up to 20 years of follow-up. Methods The lasso-Cox model was used to identify the candidate molecule. A nomogram was conducted to develop the survival model (molecular score, MS) based on the molecular features. Cox regression and Kaplan-Meier analysis were used in this study. The concordance index (C-index) was measured to compare the predicted ability between different models. The primary endpoint was overall survival (OS). Results A total of 226 patients and 23 proteins were enrolled in this study. Patients were classified into high-risk (MS-H) and low-risk (MS-L) groups based on the MS score of 227. The survival curves showed that the MS-L cohort had better 5-year and 10-year survival rates than the MS-H group (5-year OS: 51.0% vs. 8.0%; 10-year OS: 45.0% vs. 5.0%, all p < 0.001). Furthermore, multivariable analysis confirmed MS as an independent prognostic factor after eliminating the confounding factors (Hazard ratio 3.220, p < 0.001). The pT classification was confirmed to differentiate ESCC patients’ prognosis (Log-rank: p = 0.029). However, the combination of pT and MS could classify survival curves evidently (overall p < 0.001), which showed that the prognostic prediction efficiency was improved significantly by the combination of the pT and MS than by the classical pT classification (C-index: 0.656 vs. 0.539, p < 0.001). Conclusions Our study suggested an MS for significant clinical stratification of T2/3N0M0 ESCC patients to screen out subgroups with poor prognoses. Besides, the combination of pT staging and MS could predict survival more accurately for this cohort than the pT staging system alone.

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Section: Discussionmentioning

confidence: 99%

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up

Jiang,

Tian,

Guo

et al. 2024

Cancer Cell Int

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“…However, the depletion of Gr1 + MDSCs may reduce the number of MDSCs, decrease the expression levels of immune checkpoint molecules, and inhibit tumor growth, suggesting the potential roles of MDSCs in the immunosuppression and progression of ESCC[ 103 ]. Furthermore, another fundamental study reported higher levels of lnc-17Rik in MDSCs derived from the peripheral blood of EC patients, and indicated that lnc-17Rik may enhance tumor immunosuppression by increasing the expression and enhancing the activation of certain key genes involved in MDSC differentiation, such as arginase 1, cyclooxygenase 2, NOS2, and NADPH oxidase 2[ 104 ]. These findings highlight the significance of elucidating the functions of MDSCs in the TIME, and suggest potential targets for therapeutic interventions aimed at overcoming immunosuppression and improving therapeutic efficacy in patients with EC.…”

Section: Dysfunction Of Immune Cellsmentioning

confidence: 99%

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

Zhang,

Yu,

Zhao

et al. 2024

World J Gastroenterol

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As a highly invasive malignancy, esophageal cancer (EC) is a global health issue, and was the eighth most prevalent cancer and the sixth leading cause of cancer-related death worldwide in 2020. Due to its highly immunogenic nature, emer-ging immunotherapy approaches, such as immune checkpoint blockade, have demonstrated promising efficacy in treating EC; however, certain limitations and challenges still exist. In addition, tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment (TIME); thus, understanding the TIME is urgent and crucial, especially given the im-portance of an immunosuppressive microenvironment in tumor progression. The aim of this review was to better elucidate the mechanisms of the suppressive TIME, including cell infiltration, immune cell subsets, cytokines and signaling pathways in the tumor microenvironment of EC patients, as well as the downregulated expression of major histocompatibility complex molecules in tumor cells, to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies. Therefore, personalized treatments could be developed to maximize the advantages of immunotherapy.

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“…Similarly, Lnc57Rik can not only bind with the C/EBPβ isoform LAP to activate C/EBPβ but also with the WDR5 that enables the enrichment of H3K4 on the promoter regions of Arg-1, NOS2, NOX2, and COX2, eventually resulting in their transcriptional activation in tumor ( 96 ). In esophageal cancer, Lnc-17Rik could act as decoy to dissociate C/EBPβ isoform LAP to activate C/EBPβ and as a scaffold to guide WDR5 transfer to the promoter region of MDSC-specific molecules, ultimately promoting the immunosuppressive function of MDSCs ( 97 ). The knockdown of Pvt1 significantly suppressed MDSC-mediated immunosuppression on T cells in vitro by decreasing the level of ROS and Arg1 ( 98 ).…”

Section: Lncrnas and Local Immunosuppressive Tumor Microenvironmentmentioning

confidence: 99%

Exploring the regulatory role of lncRNA in cancer immunity

Zhan,

Xian

2023

Front. Oncol.

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Imbalanced immune homeostasis in cancer microenvironment is a hallmark of cancer. Increasing evidence demonstrated that long non-coding RNAs (lncRNAs) have emerged as key regulatory molecules in directly blocking the cancer immunity cycle, apart from activating negative regulatory pathways for restraining tumor immunity. lncRNAs reshape the tumor microenvironment via the recruitment and activation of innate and adaptive lymphoid cells. In this review, we summarized the versatile mechanisms of lncRNAs implicated in cancer immunity cycle, including the inhibition of antitumor T cell activation, blockade of effector T cell recruitment, disruption of T cell homing, recruitment of immunosuppressive cells, and inducing an imbalance between antitumor effector cells (cytotoxic T lymphocytes, M1 macrophages, and T helper type 1 cells) versus immunosuppressive cells (M2 macrophages, T helper type 2 cells, myeloid derived suppressor cells, and regulatory T cells) that infiltrate in the tumor. As such, we would highlight the potential of lncRNAs as novel targets for immunotherapy.

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Lnc-17Rik promotes the immunosuppressive function of Myeloid-Derived suppressive cells in esophageal cancer

Cited by 6 publications

References 60 publications

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up

The molecular characteristics could supplement the staging system of pT2/T3N0M0 esophageal squamous cell carcinoma: a translational study based on a cohort with over 20 years of follow-up

Mechanisms of tumor immunosuppressive microenvironment formation in esophageal cancer

Exploring the regulatory role of lncRNA in cancer immunity

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