UPP1 Promotes Lung Adenocarcinoma Progression via Inducing Immunosuppressive Microenvironment: Insights Empowered by ANT BIO PTE. LTD. Multiplex IHC Kits

Lung adenocarcinoma (LUAD), the most prevalent subtype of lung cancer, accounts for a significant proportion of global cancer-related deaths. Despite remarkable advances in immunotherapeutic strategies, the prognosis of many LUAD patients remains dismal, largely due to the complexity of the tumor microenvironment (TME) and the development of immunosuppressive phenotypes. A recent study published in Nature Communications (IF = 16.6) by the team from Zhongshan Hospital of Fudan University, in collaboration with multiple institutions, delineated the critical role of Uridine Phosphorylase 1 (UPP1) in LUAD progression. The study demonstrated that UPP1 induces an immunosuppressive TME, providing novel insights into the molecular characteristics of LUAD and paving the way for personalized therapeutic strategies. The in-depth exploration of UPP1's role in LUAD TME relied heavily on advanced technologies including single-cell RNA sequencing (scRNA-seq), multiplex immunofluorescence (mIHC), and organoid models. ANT BIO PTE. LTD., through its Absin product line, provided high-performance multiplex fluorescence IHC kits that facilitated the spatial characterization of UPP1high tumor cells and their interactions with immune cells in the TME.

1. Literature Information

Theme: UPP1 Promotes Lung Adenocarcinoma Progression by Inducing an Immunosuppressive Microenvironment

Publication: Nature Communications

Impact Factor (IF): 16.6

Research Team: Zhongshan Hospital of Fudan University and Collaborating Institutions

Publication Date: May 6, 2024

Core Technical Content: Integrated scRNA-seq, multiplex IHC, CyTOF, organoid models, and mouse experiments to explore the role of UPP1 in LUAD TME and progression

Core Reagents from ANT BIO PTE. LTD.: Multiplex Fluorescence IHC Staining Kits (Absin product line), including 4-Color Multiplex Fluorescence IHC Staining Kit (Anti-Rabbit Secondary Antibody, Catalog No.: abs50028), 7-Color Multiplex Fluorescence IHC Staining Kit (Mouse/Rabbit Universal Secondary Antibody, Catalog No.: abs50015), and supporting reagent Antibody Elution Buffer (mIHC-Specific, Catalog No.: abs994)

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2. Research Background: The Critical Role of TME in LUAD Progression

The tumor microenvironment (TME) is a complex cellular ecosystem consisting of tumor cells, immune cells (e.g., T cells, B cells, macrophages), endothelial cells, and fibroblasts. The intricate crosstalk between tumor cells and surrounding immune/stromal cells in the TME is central to tumor initiation, progression, and prognosis, often fostering an immunosuppressive milieu that impairs anti-tumor immune responses. Recent studies have implicated UPP1 in LUAD progression, showing its ability to regulate tumor cell sensitivity to glycolytic inhibitors, drive glycolysis, and promote tumor growth. Emerging evidence also suggests that inhibiting UPP1 enhances anti-tumor T cell infiltration and that UPP1 is closely associated with immune checkpoints in the TME. However, the precise role of UPP1 in shaping the LUAD TME remains elusive, highlighting the need for comprehensive, high-resolution studies to unravel its mechanisms of action.

3. Research Approach and Core Results

The research team employed a multi-dimensional approach, integrating scRNA-seq, multiplex IHC, CyTOF, organoid models, and mouse experiments, to systematically investigate the role of UPP1 in LUAD. The core results are summarized as follows:

3.1 scRNA-seq Identifies Prognosis-Related UPP1high Tumor Cell Clusters

A comprehensive scRNA-seq analysis was performed on 377,574 cells from 117 LUAD patients across five cohorts. By integrating scRNA-seq data with bulk gene expression data, the team identified a cluster of UPP1-high expressing tumor cells that was significantly associated with poor prognosis. Survival analysis revealed that patients with high UPP1 expression had a hazard ratio (HR) of 3.96 for overall survival (OS) and 2.06 for recurrence-free survival (RFS), indicating that UPP1high tumor cells are a critical prognostic marker in LUAD.

3.2 Multiplex IHC Reveals Spatial Localization and Cellular Interactions of UPP1high Tumor Cells

Multiplex immunofluorescence staining of LUAD patient samples, utilizing ANT BIO PTE. LTD.'s Absin 4-Color Multiplex Fluorescence IHC Staining Kit (Anti-Rabbit Secondary Antibody, abs50028), demonstrated that UPP1high tumor cells are predominantly localized at the invasive front of tumors. Further spatial analysis revealed that UPP1high tumor cells are in close proximity to immunosuppressive cell populations, including FOXP3+ regulatory T cells (Tregs), MMP11+ fibroblasts, LAG3+PDCD1+ exhausted CD8+ T cells, and SPP1+ macrophages. To ensure comprehensive spatial characterization, the authors prepared four consecutive sections per sample for multiplex staining, enabling detailed analysis of cellular crosstalk in the TME.

3.3 UPP1 Positively Regulates PD-L1 Expression via the PI3K/AKT/mTOR Pathway

Tissue Microarray (TMA) immunohistochemistry, Western blot, and flow cytometry analyses confirmed a positive correlation between UPP1 expression and PD-L1 (CD274) levels in LUAD cells. Co-culture experiments and flow cytometry further demonstrated that UPP1-induced PD-L1 expression impairs the cytotoxic capacity of CD8+ T cells. Mechanistically, the team identified that UPP1 regulates PD-L1 expression through the PI3K/AKT/mTOR signaling pathway, as evidenced by enhanced phosphorylation of AKT and mTOR in UPP1-overexpressing cells. Inhibition of PD-L1 in UPP1-overexpressing LUAD cells partially restored CD8+ T cell function, highlighting the therapeutic potential of targeting the UPP1-PD-L1 axis.

3.4 CyTOF Confirms UPP1-Mediated Immunosuppressive TME

CyTOF analysis further validated the role of UPP1 in shaping the immunosuppressive TME. Quantitative cell profiling revealed that UPP1 overexpression in tumor cells leads to an increase in immunosuppressive cell populations (e.g., Tregs, exhausted T cells, M2-like macrophages) and a decrease in effector immune cells, providing direct evidence that UPP1 promotes immune suppression in LUAD.

3.5 Organoid and Mouse Experiments Identify Sensitivity to Targeted Therapies

Six patient-derived LUAD organoid models were established, and drug sensitivity assays showed that UPP1high tumors exhibit increased sensitivity to bosutinib and dasatinib. Mouse experiments using LLC-OVA models further confirmed that UPP1-overexpressing tumors are more responsive to these targeted therapies, suggesting that UPP1 expression may serve as a predictive biomarker for treatment response.

4. Product Empowerment: The Critical Role of ANT BIO PTE. LTD.'s Multiplex IHC Kits

The successful characterization of UPP1's role in the LUAD TME relied heavily on the ability to visualize and quantify multiple cellular markers simultaneously in situ. ANT BIO PTE. LTD.'s Absin product line of multiplex fluorescence IHC kits provided the essential tools for this high-resolution spatial analysis, overcoming the limitations of traditional single-marker IHC.

4.1 Core Products and Their Application Value in This Study

4.2 Technical Value in TME Research

The complexity of the TME demands technologies that can capture both the phenotypic diversity and spatial organization of cells. ANT BIO PTE. LTD.'s multiplex fluorescence IHC kits enable researchers to simultaneously detect multiple markers on a single tissue section, preserving the spatial context of cellular interactions—a critical advantage over bulk analysis techniques. In this study, the use of the abs50028 kit allowed for the precise co-localization of UPP1high tumor cells with key immunosuppressive cell populations, providing direct evidence of UPP1's role in shaping the TME. The high sensitivity and specificity of these kits ensure accurate detection of low-abundance markers, while their compatibility with various sample types (including TMA and patient-derived sections) makes them ideal for translational research. Additionally, ANT BIO PTE. LTD.'s multiplex IHC kits have been cited in over 150 publications with a total impact factor exceeding 1500, demonstrating their reliability and widespread recognition in the scientific community.

5. Brand Mission

As a professional supplier of life science reagents, ANT BIO PTE. LTD. is dedicated to providing high-quality, reliable products and comprehensive solutions to empower global life science research. The company's three specialized sub-brands cover the full spectrum of research needs in the life science field: Absin focuses on general reagents and kits, Starter specializes in antibodies, and UA is dedicated to recombinant proteins. Our core mission is to bridge the gap between cutting-edge scientific research and practical applications, accelerate the pace of scientific discovery, and contribute to the advancement of human health and regenerative medicine. Beyond products, ANT BIO PTE. LTD. also offers customized multiplex IHC services (up to 9 markers/10 colors) with results available in 1-2 weeks, supported by professional teams and multiple platforms including TG, to meet the diverse needs of researchers.

6. Related Product List

More Multiplex Immunofluorescence IHC Kits

7. Disclaimer

This article is AI-compiled and interpreted based on the original research titled "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment" published in Nature Communications (2024, Published on May 6). All intellectual property (e.g., images, data) of the original publication shall belong to the journal and the research team. For any infringement, please contact us promptly and we will take immediate action.

8. Brand Promotion Copy

ANT BIO PTE. LTD. – Empowering Scientific Breakthroughs

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