scholarly journals FGL2 is positively correlated with enhanced antitumor responses mediated by T cells in lung adenocarcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8654
Author(s):  
Kai Yuan ◽  
Yanyan Feng ◽  
Hesong Wang ◽  
Lu Zhao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Lung Adenocarcinoma ◽  
T Cell Activation ◽  
Genetic Alterations ◽  
Functional Enrichment ◽  
High Expression ◽  
Expression Level ◽  
High Expression Level

Lung cancer is the most common malignant tumor, accounting for 25% of cancer-related deaths and 14% of new cancers worldwide. Lung adenocarcinoma is the most common type of pulmonary cancer. Although there have been some improvements in the traditional therapy of lung cancer, the outcome and prognosis of patients remain poor. Lung cancer is the leading cause of cancer-related deaths worldwide, with 1.8 million new cases being diagnosed each year. Precision medicine based on genetic alterations is considered a new strategy of lung cancer treatment that requires highly specific biomarkers for precision diagnosis and treatment. Fibrinogen-like protein 2 (FGL2) plays important roles in both innate and adaptive immunity. However, the diagnostic value of FGL2 in lung cancer is largely unknown. In this study, we systematically investigated the expression profile and potential functions of FGL2 in lung adenocarcinoma. We used the TCGA and Oncomine datasets to compare the FGL2 expression levels between lung adenocarcinoma and adjacent normal tissues. We utilized the GEPIA, PrognoScan and Kaplan-Meier plotter databases to analyze the relationship between FGL2 expression and the survival of lung adenocarcinoma patients. Then, we investigated the potential roles of FGL2 in lung adenocarcinoma with the TIMER database and functional enrichment analyses. We found that FGL2 expression was significantly lower in lung adenocarcinoma tissue compared with adjacent normal tissue. A high expression level of FGL2 was correlated with better prognostic outcomes of lung adenocarcinoma patients, including overall survival and progression-free survival. FGL2 was positively correlated with the infiltration of immune cells, including dendritic cells, CD8+ T cells, macrophages, B cells, and CD4+ T cells, in lung adenocarcinoma. Functional enrichment analyses also showed that a high expression level of FGL2 was positively correlated with enhanced T cell activities, especially CD8+ T cell activation. Thus, we propose that high FGL2 expression, which is positively associated with enhanced antitumor activities mediated by T cells, is a beneficial marker for lung adenocarcinoma treatment outcomes.

scholarly journals Immunogenomic Gene Signature of Cell-Death Associated Genes with Prognostic Implications in Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 155
Author(s):  
Pankaj Ahluwalia ◽  
Meenakshi Ahluwalia ◽  
Ashis K. Mondal ◽  
Nikhil Sahajpal ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Risk Group ◽  
High Risk Group ◽  
Free Survival ◽  
Cell Death Pathways

Lung cancer is one of the leading causes of death worldwide. Cell death pathways such as autophagy, apoptosis, and necrosis can provide useful clinical and immunological insights that can assist in the design of personalized therapeutics. In this study, variations in the expression of genes involved in cell death pathways and resulting infiltration of immune cells were explored in lung adenocarcinoma (The Cancer Genome Atlas: TCGA, lung adenocarcinoma (LUAD), 510 patients). Firstly, genes involved in autophagy (n = 34 genes), apoptosis (n = 66 genes), and necrosis (n = 32 genes) were analyzed to assess the prognostic significance in lung cancer. The significant genes were used to develop the cell death index (CDI) of 21 genes which clustered patients based on high risk (high CDI) and low risk (low CDI). The survival analysis using the Kaplan–Meier curve differentiated patients based on overall survival (40.4 months vs. 76.2 months), progression-free survival (26.2 months vs. 48.6 months), and disease-free survival (62.2 months vs. 158.2 months) (Log-rank test, p < 0.01). Cox proportional hazard model significantly associated patients in high CDI group with a higher risk of mortality (Hazard Ratio: H.R 1.75, 95% CI: 1.28–2.45, p < 0.001). Differential gene expression analysis using principal component analysis (PCA) identified genes with the highest fold change forming distinct clusters. To analyze the immune parameters in two risk groups, cytokines expression (n = 265 genes) analysis revealed the highest association of IL-15RA and IL 15 (> 1.5-fold, p < 0.01) with the high-risk group. The microenvironment cell-population (MCP)-counter algorithm identified the higher infiltration of CD8+ T cells, macrophages, and lower infiltration of neutrophils with the high-risk group. Interestingly, this group also showed a higher expression of immune checkpoint molecules CD-274 (PD-L1), CTLA-4, and T cell exhaustion genes (HAVCR2, TIGIT, LAG3, PDCD1, CXCL13, and LYN) (p < 0.01). Furthermore, functional enrichment analysis identified significant perturbations in immune pathways in the higher risk group. This study highlights the presence of an immunocompromised microenvironment indicated by the higher infiltration of cytotoxic T cells along with the presence of checkpoint molecules and T cell exhaustion genes. These patients at higher risk might be more suitable to benefit from PD-L1 blockade or other checkpoint blockade immunotherapies.

scholarly journals The immune-suppressive landscape in lepromatous leprosy revealed by single-cell RNA sequencing

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Zihao Mi ◽  
Zhenzhen Wang ◽  
Xiaotong Xue ◽  
Tingting Liu ◽  
Chuan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Lepromatous Leprosy ◽  
High Expression ◽  
Expression Level ◽  
Intracellular Bacteria ◽  
Monocyte Subset ◽  
Single Cell Rna Sequencing ◽  
High Expression Level

AbstractLepromatous leprosy (L-LEP), caused by the massive proliferation of Mycobacterium leprae primarily in macrophages, is an ideal disease model for investigating the molecular mechanism of intracellular bacteria evading or modulating host immune response. Here, we performed single-cell RNA sequencing of both skin biopsies and peripheral blood mononuclear cells (PBMCs) of L-LEP patients and healthy controls. In L-LEP lesions, we revealed remarkable upregulation of APOE expression that showed a negative correlation with the major histocompatibility complex II gene HLA-DQB2 and MIF, which encodes a pro-inflammatory and anti-microbial cytokine, in the subset of macrophages exhibiting a high expression level of LIPA. The exhaustion of CD8+ T cells featured by the high expression of TIGIT and LAG3 in L-LEP lesions was demonstrated. Moreover, remarkable enhancement of inhibitory immune receptors mediated crosstalk between skin immune cells was observed in L-LEP lesions. For PBMCs, a high expression level of APOE in the HLA-DRhighFBP1high monocyte subset and the expansion of regulatory T cells were found to be associated with L-LEP. These findings revealed the primary suppressive landscape in the L-LEP patients, providing potential targets for the intervention of intracellular bacteria caused persistent infections.

scholarly journals COL1A1 is a prognostic biomarker and correlated with immune infiltrates in lung cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11145
Author(s):  
Qishun Geng ◽  
Zhibo Shen ◽  
Lifeng Li ◽  
Jie Zhao
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
Dendritic Cell ◽  
Cd4 T Cells ◽  
Malignant Tumors ◽  
Functional Enrichment ◽  
Expression Level ◽  
Normal Lung ◽  
Hub Genes ◽  
Clinical Prognosis

Objective Lung cancer (LC) is one of the top ten malignant tumors and the first leading cause of cancer-related death among both men and women worldwide. It is imperative to identify immune-related biomarkers for early LC diagnosis and treatment. Methods Three Gene Expression Omnibus (GEO) datasets were selected to acquire the differentially expressed genes(DEGs) between LC and normal lung samples through GEO2R tools of NCBI. To identify hub genes, the DEGs were performed functional enrichment analysis, the protein–protein interaction (PPI) network construction, and Lasso regression. Then, a nomogram was constructed to predict the prognosis of patients with carcinoma based on hub genes. We further evaluated the influence of COL1A1 on clinical prognosis using GSE3141, GSE31210, and TCGA database. Also, the correlations between COL1A1 and cancer immune infiltrates and the B7-CD28 family was investigated via TIMER and GEPIA. Further analysis of immunohistochemistry shown that the COL1A1 expression level is positively correlated with CD276 expression level. Results By difference analysis, there were 340 DEGs between LC and normal lung samples. Then, we picked out seven hub genes, which were identified as components of the risk signature to divide LC into low and high-risk groups. Among them, the expression of COL1A1 is highly correlated with overall survival(OS) and progression-free survival (PFS) (p < 0.05). Importantly, there is a moderate to strong positive relationships between COL1A1 expression level and infiltration level of CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level. Conclusion These findings suggest that COL1A1 is correlated with prognosis and immune infiltrating levels, including CD4+ T cells, Macrophage, Neutrophil, and Dendritic cell, as well as CD276 expression level, indicating COL1A1 can be a potential immunity-related biomarker and therapeutic target in LC.

scholarly journals A Role of Suppressor of Cytokine Signaling 3 (SOCS3/CIS3/SSI3) in CD28-mediated Interleukin 2 Production

2003 ◽  
Vol 197 (4) ◽  
pp. 425-436 ◽  
Author(s):  
Akira Matsumoto ◽  
Yoh-ichi Seki ◽  
Ryosuke Watanabe ◽  
Katsuhiko Hayashi ◽  
James A. Johnston ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Interleukin 2 ◽  
Sh2 Domain ◽  
Janus Kinase ◽  
Expression Level ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Cd28 Costimulation

Suppressor of cytokine signaling (SOCS)3 has been characterized as a negative feedback regulator in cytokine-mediated Janus kinase signal transducer and activator of transcription signaling. However, this study shows that T cells from transgenic mice expressing SOCS3 exhibit a significant reduction in interleukin (IL)-2 production induced by T cell receptor cross-linking when T cells are costimulated with CD28. Decreased protein expression in SOCS3+/− mice enhanced CD28-mediated IL-2 production, clearly indicating the correlation between expression level of SOCS3 and IL-2 production ability. The SOCS3 protein interacted with phosphorylated CD28 through its SH2 domain but not the kinase inhibitory region. In addition, a point mutation in the SOCS3 SH2 domain attenuated the inhibition of CD28 function in IL-2 promoter activation. Committed T helper (Th)2 cells exclusively expressed SOCS3 and production of Th2 cytokines, such as IL-4 and IL-5, was much less dependent on CD28 costimulation compared with interferon γ and IL-2 production in Th1 cells. Consistent with this notion, the expression level of SOCS3 in early T cell activation influenced the ability of IL-2 production induced by CD28 costimulation. Therefore, the SOCS3 may play an alternative role in prohibiting excessive progression of CD28-mediated IL-2 production.

CD56+ T-cell Prolymphocytic Leukemia Showing a High Expression Level ofTCL1Oncogene: A Case Report with a Review of the Literature

2006 ◽  
Vol 41 (2) ◽  
pp. 129
Author(s):  
Hyeong-Kee Yun ◽  
Myung-Geun Shin ◽  
Hyeoung-Joon Kim ◽  
Hye-Ran Kim ◽  
Ji-Young Park ◽  
...  
Keyword(s):  
Case Report ◽  
T Cell ◽  
High Expression ◽  
Expression Level ◽  
Review Of The Literature ◽  
Prolymphocytic Leukemia ◽  
High Expression Level

scholarly journals Epigenetic modulation of immune synaptic-cytoskeletal networks potentiates γδ T cell-mediated cytotoxicity in lung cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rueyhung R. Weng ◽  
Hsuan-Hsuan Lu ◽  
Chien-Ting Lin ◽  
Chia-Chi Fan ◽  
Rong-Shan Lin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Cancer Cells ◽  
T Cell Activation ◽  
Actin Polymerization ◽  
Γδ T Cells ◽  
Human Lung Cancer ◽  
Γδ T Cell ◽  
Cancer Management

Abstractγδ T cells are a distinct subgroup of T cells that bridge the innate and adaptive immune system and can attack cancer cells in an MHC-unrestricted manner. Trials of adoptive γδ T cell transfer in solid tumors have had limited success. Here, we show that DNA methyltransferase inhibitors (DNMTis) upregulate surface molecules on cancer cells related to γδ T cell activation using quantitative surface proteomics. DNMTi treatment of human lung cancer potentiates tumor lysis by ex vivo-expanded Vδ1-enriched γδ T cells. Mechanistically, DNMTi enhances immune synapse formation and mediates cytoskeletal reorganization via coordinated alterations of DNA methylation and chromatin accessibility. Genetic depletion of adhesion molecules or pharmacological inhibition of actin polymerization abolishes the potentiating effect of DNMTi. Clinically, the DNMTi-associated cytoskeleton signature stratifies lung cancer patients prognostically. These results support a combinatorial strategy of DNMTis and γδ T cell-based immunotherapy in lung cancer management.

scholarly journals Antitumour effect of neoantigen-reactive T cells induced by RNA mutanome vaccine in mouse lung cancer

2021 ◽  
Author(s):  
Jiaxing Sun ◽  
Jing Zhang ◽  
Haiyan Hu ◽  
Huan Qin ◽  
Ximing Liao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Therapeutic Approach ◽  
Tumour Progression ◽  
T Cell Response ◽  
Mouse Lung ◽  
In Vivo Model ◽  
Antitumour Effect

Abstract Purpose Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the antitumour effect of neoantigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer. Methods We predicted candidate neoantigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neoantigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments. Results We identified 10 nonsynonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8–24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression. Conclusions NRT cells induced by RNA mutanome vaccine exert a significant antitumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.

scholarly journals Lysophosphatidic Acid Receptor 6 (LPAR6) Is a Potential Biomarker Associated with Lung Adenocarcinoma

2021 ◽  
Vol 18 (21) ◽  
pp. 11038
Author(s):  
Jian He ◽  
Rui Gao ◽  
Mei Meng ◽  
Miao Yu ◽  
Chengrong Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cell ◽  
Lung Adenocarcinoma ◽  
Mrna Expression ◽  
Lysophosphatidic Acid ◽  
Expression Level ◽  
Mrna Expression Level ◽  
Acid Receptor ◽  
Lysophosphatidic Acid Receptor

LPAR6 is the most recently determined G-protein-coupled receptor of the lysophosphatidic acid receptor, and very few of studies have demonstrated the performance of LPAR6 in cancers. Moreover, the relationship of LPAR6 to the potential of prognosis and tumor infiltration immune cells in different types of cancer are still unclarified. In this study, the mRNA expression of LPAR6 and its clinical characteristics were evaluated on various databases. The association between LPAR6 and immune infiltrates of various types of cancer were investigated via TIMER. Immunohistochemistry (IHC) for LPAR6 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tissue microarray with patients’ information was detected. We constructed a systematic prognostic landscape in a variety of types of cancer base on the expression level of mRNA. We enclosed that higher LPAR6 mRNA expression level was associated with better overall survival in some types of malignancy. Moreover, LPAR6 significantly affects the prognostic potential of various cancers in The Cancer Genome Atlas Program (TCGA), especially in lung cancer. Tissue microarrays of lung cancer patient cohorts demonstrated that a higher protein level of LPAR6 was correlated to better overall survival of LUAD rather than LUSC cohorts. Further research indicated that the underlying mechanism of this phenome might be the mRNA expression level of LPAR6 was positively associated to infiltrating statuses of devious immunocytes in LUAD rather than in LUSC, that is, LPAR6 expression potentially contributes to the activation and recruiting of T cells (CD8+ T, naive T, effector T cell) and NK cells and inactivates Tregs, decreases T cell exhaustion and regulates T-helper (Th) cells in LUAD. Our discovery implies that LPAR6 is associated with prognostic potential and immune-infiltrating levels in LUAD. These discoveries imply that LPAR6 could be a promising novel biomarker for indicating the prognosis potential of LUAD patients.

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