Cancer-cell-intrinsic mechanisms regulate MDSCs through cytokine networks

Zhang, Yuting; Murphy, Seán; Lü, Xin

doi:10.1016/bs.ircmb.2022.09.001

Cited by 2 publications

(3 citation statements)

References 119 publications

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Section: Introductionmentioning

confidence: 99%

“…Immunomodulators includes immunoinhibitors and immunostimulators, More and more studies had shown that different immune phenotypes in solid tumors are closely related to gene types. 9,10 A Protein-coding gene, Leucyl-tRNA synthetase 1 (LARS1), also named LARS, is a member of the aminoacyl-tRNA synthetase class I family. L-leucine ligation to tRNA is catalyzed by the encoded enzyme.…”

Section: Introductionmentioning

confidence: 99%

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LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma

Fan,

Qin,

et al. 2024

IJGM

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Purpose To study the relationship between LARS1 expression and immune infiltration and prognosis in hepatocellular carcinoma (HCC). Patients and Methods The clinical characteristics together with LARS1 expression levels were obtained from the TCGA database. Immunohistochemistry confirmed LARS1 expression levels in paraneoplastic and tumor tissues. To investigate LARS1-related downstream molecules, a network of protein-protein interactions (PPIs) and the Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) were built. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathways associated with LARS1 expression, whereas Single-sample GSEA (ssGSEA) was applied to perform an association study between immune infiltration and LARS1 gene expression. The TISCH Database and the TISIDB database were used to compare the difference of LARS1 expression in hepatocellular carcinoma and immunomodulators. Results In comparison to that in normal tissues, the LARS1 expression level was elevated in tumor tissues. LARS1 expression exhibited substantial correlation with AFP, Histologic grade, pathologic stage, Residual tumor, and Vascular invasion in HCC. Higher LARS1 expression in HCC was linked to lower progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS). According to the GO/KEGG study, the important biological process (neutral lipid metabolic process), cellular component (triglyceride-rich plasma lipoprotein), molecular functions (lipase inhibitor activity), and KEGG pathway (cholesterol metabolism) could be a probable function mechanism in promoting HCC. Various pathways as per GSEA revealed that they were enriched in samples with elevated LARS1 expression. The expression level of LARS1 in malignant tumor cells after immunotherapy was significantly higher than that before immunotherapy. LARS1 was also remarkably linked to the infiltration level and the immunomodulators. Conclusion LARS1 can be used as a biomarker of HCC, which is associated to immune infiltration of HCC.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma

Fan,

Qin,

et al. 2024

IJGM

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“…Certain cancers, such as prostate cancer, exhibit notable de novo resistance to immunotherapy [2]. Myeloid-derived suppressor cells (MDSCs) have been identified as a critical contributor to immunosuppression in the tumor microenvironment [3,4]. Extensive studies have revealed MDSCs to be a heterogeneous population of cells that expand during cancer and other diseases and are characterized by their ability to suppress T cell responses and promote tumor growth [5].…”

Section: Introductionmentioning

confidence: 99%

Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling

Zhang,

Hu,

Zhang

et al. 2024

Cells

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Myeloid-derived suppressor cells (MDSCs) play an essential role in suppressing the antitumor activity of T lymphocytes in solid tumors, thus representing an attractive therapeutic target to enhance the efficacy of immunotherapy. However, the differences in protein expression between MDSCs and their physiological counterparts, particularly polymorphonuclear neutrophils (PMNs), remain inadequately characterized, making the specific identification and targeting of MDSCs difficult. PMNs and PMN-MDSCs share markers such as CD11b+CD14−CD15+/CD66b+, and some MDSC-enriched markers are emerging, such as LOX-1 and CD84. More proteomics studies are needed to identify the signature and markers for MDSCs. Recently, we reported the induced differentiation of isogenic PMNs or MDSCs (referred to as iPMNs and iMDSCs, respectively) from the human promyelocytic cell line HL60. Here, we profiled the global proteomics and membrane proteomics of these cells with quantitative mass spectrometry, which identified a 41-protein signature (“cluster 6”) that was upregulated in iMDSCs compared with HL60 and iPMN. We further integrated our cell line-based proteomics data with a published proteomics dataset of normal human primary monocytes and monocyte-derived MDSCs induced by cancer-associated fibroblasts. The analysis identified a 38-protein signature that exhibits an upregulated expression pattern in MDSCs compared with normal monocytes or PMNs. These signatures may provide a hypothesis-generating platform to identify protein biomarkers that phenotypically distinguish MDSCs from their healthy counterparts, as well as potential therapeutic targets that impair MDSCs without harming normal myeloid cells.

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Cancer-cell-intrinsic mechanisms regulate MDSCs through cytokine networks

Cited by 2 publications

References 119 publications

LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma

LARS1 is a Prognostic Biomarker and Exhibits a Correlation with Immune Infiltrates in Hepatocellular Carcinoma

Protein Signature Differentiating Neutrophils and Myeloid-Derived Suppressor Cells Determined Using a Human Isogenic Cell Line Model and Protein Profiling

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