XBP1 impacts lung adenocarcinoma progression by promoting plasma cell adaptation to the tumor microenvironment

Zhong, Zhaoqian; Wang, Junhao; Han, Qizheng; Lin, Hong; Luo, Haihua; Guo, Danyan; Liu, Aihua

doi:10.3389/fgene.2022.969536

Cited by 4 publications

(3 citation statements)

References 73 publications

(78 reference statements)

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“…Xbp1 regulon displayed the highest activity in MGUS EC ( Figure 3F; Figure S7B-C ). Xbp1 is a stress-inducible transcription factor, whose role in deregulation of the immune microenvironment of various cancers 26 has been described. Xbp1 has also been reported to promote endothelial proliferation and angiogenesis through VEGF signaling in EC 27 .…”

Section: Resultsmentioning

confidence: 99%

Transcriptional Remodeling of the Stromal and Endothelial Microenvironment in MGUS to Multiple Myeloma Progression

Cenzano,

Cócera,

Bantan

et al. 2024

Preprint

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Despite therapeutic advancements, Multiple Myeloma (MM) remains an incurable disease. To characterize the role that deregulation of the Bone Marrow (BM) microenvironment may have in the transition from healthy to Monoclonal Gammopathy of Undetermined Significance (MGUS), and from MGUS to MM, we performed single-cell RNA sequencing (scRNA-seq) of mesenchymal stromal cells (MSC) and endothelial cells (EC) from two mouse models, BIcgamma and MIcgamma, that recapitulate the principal clinical, genetic, and immunological characteristics of MGUS and MM patients. Our results identify distinct transcriptional dynamics between MSC and EC. While EC acquires a stress state during MGUS, a proliferating and angiogenic profile characterizes MM. On the other hand, MSC compromised their differentiation potential, exhibiting a more inflammatory profile that initiates from the MGUS stage. Interestingly, we identified interferon (IFN)-related myeloma signature in malignant EC of the BIcgamma model, which is also expressed in MSC but not observed in the most aggressive MIcgamma model and can be identified in a subgroup of MM patients. The analysis of the MSC and EC interactions with PC revealed stage-specific interactions of relevance for angiogenesis, immunomodulation, and MM extravasation. Finally, the translational relevance of our results in humans was confirmed on MSC from newly diagnosed patients at different stages of the disease. In summary, these results indicate a remodeling of the non-hematopoietic BM microenvironment in myeloma progression, providing potential targets at the tumor-niche interface that may hold clinical significance and complement existing immunotherapies.

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Section: Resultsmentioning

confidence: 99%

Transcriptional Remodeling of the Stromal and Endothelial Microenvironment in MGUS to Multiple Myeloma Progression

Cenzano,

Cócera,

Bantan

et al. 2024

Preprint

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“…The prognostic markers and the indications for prognosis in these studies are summarized in Table 2 . 36 , 44 , 45 , 47 – 49 , 55 – 89 DEGs and their combined prognostic model were the most common types of prognostic markers in these studies. For example, one study identified nine cancer-specific DEGs (CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6) and established a prognostic risk model in combination with clinical factors.…”

Section: The Prognostic Time Markers For Luadmentioning

confidence: 91%

Unraveling the tumor immune microenvironment of lung adenocarcinoma using single-cell RNA sequencing

Song,

Gong,

Wang

et al. 2024

Ther Adv Med Oncol

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Tumor immune microenvironment (TIME) and its indications for lung cancer patient prognosis and therapeutic response have become new hotspots in cancer research in recent years. Tumor cells, immune cells, various regulatory factors, and their interactions in the TIME have been suggested to commonly influence lung cancer development and therapeutic outcome. The heterogeneity of TIME is composed of dynamic immune-related components, including various cancer cells, immune cells, cytokine/chemokine environments, cytotoxic activity, or immunosuppressive factors. The specific composition of cell subtypes may facilitate or hamper the response to immunotherapy and influence patient prognosis. Various markers have been found to stratify the patient prognosis or predict the therapeutic outcome. In this article, we systematically reviewed the recent advancement of TIME studies in lung adenocarcinoma (LUAD) using single-cell RNA sequencing (scRNA-seq) techniques, with specific focuses on the roles of TIME in LUAD development, TIME heterogeneity, indications of TIME in patient prognosis and therapeutic response during immunotherapy and drug resistance. The main findings in TIME heterogeneity and relevant markers or models for prognosis stratification and response prediction have been summarized. We hope that this review provides an overview of TIME status in LUAD and an inspiration for future development of strategies and biomarkers in LUAD treatment.

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“…Lung adenocarcinoma (LUAD) is a malignant tumor with the highest mortality rate worldwide. Non-small cell lung carcinoma (NSCLC) accounts for about 85% of all lung carcinoma, and adenocarcinoma is the main pathological type of NSCLC, accounting for about 60% of NSCLC (1). Most LUAD patients are diagnosed at a late stage, and therefore, lose the opportunity for treatment.…”

Section: Introductionmentioning

confidence: 99%

The relationship between tumor infiltrating immune cells and the prognosis of patients with lung adenocarcinoma

Tong¹,

Wang²,

Liu³

et al. 2023

J Thorac Dis

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Background: To depict the immune infiltration characteristics of tumor cells in patients with lung adenocarcinoma (LUAD) and evaluate the predictive value and significance of tumor immune cells on the prognosis of LUAD patients. Methods:The clinical characteristics and transcriptome of LUAD patients were obtained from The Cancer Genome Atlas (TCGA), and the immune cell abundance in LUAD tissue was evaluated using the CIBERSORT algorithm. We created a simplified immune cell-based Cox regression model according to the survival status of patients and clarified the correlation between the survival status of patients and seven types of immune cells. An immune cell-based risk prediction model was created by Cox proportional hazards regression. Subsequently, the gene expression profile of LUAD patients was obtained from the Gene Expression Omnibus (GEO) database to validate the tumor immune infiltration and patient prognosis prediction model attained using the CIBERSORT algorithm.Results: The abundance of 22 tumor-infiltrating immune cells in these patients was detected using the CIBERSORT algorithm. According to Pearson correlation analysis, the immune cells appeared to be closely related to each other. The immune cell composition was remarkably different between the LUAD tumor tissue and paracancerous tissue. The simplified COX model showed that seven kinds of immune cells have predictive value for the prognosis and survival status of LUAD. The receiver operating characteristic curve (ROC) curve confirmed that the prediction model performed well for 1-, 3-, and 5-year survival status. The calibration curve suggested that the prediction model was consistent with the clinical results. Correlation analysis revealed that the clinical features were significantly related to immune cell infiltration. A total of 246 LUAD specimens were from the GEO database, and the risk score model suggested that high risk scores were indicative of a poor prognosis. Finally, enzyme-linked immunosorbent assay (ELISA) revealed that the expressions of tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), IL-6, and interferon-γ (IFN-γ) in tumor tissues were remarkably higher compared with those in adjacent tissues.Conclusions: There is a close correlation between the tumor-infiltrating immune cells and the prognosis and clinical characteristics of LUAD patients. The risk score model based on TCGA and GEO designed in this study can be applied in clinical practice.

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XBP1 impacts lung adenocarcinoma progression by promoting plasma cell adaptation to the tumor microenvironment

Cited by 4 publications

References 73 publications

Transcriptional Remodeling of the Stromal and Endothelial Microenvironment in MGUS to Multiple Myeloma Progression

Transcriptional Remodeling of the Stromal and Endothelial Microenvironment in MGUS to Multiple Myeloma Progression

Unraveling the tumor immune microenvironment of lung adenocarcinoma using single-cell RNA sequencing

The relationship between tumor infiltrating immune cells and the prognosis of patients with lung adenocarcinoma

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