Serum and Glucocorticoid-Inducible Kinase 1 (SGK1) in NSCLC Therapy

Abstract Background Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631. Methods In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis. Results In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003). Conclusions Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

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Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis

10.21203/rs.3.rs-32312/v3 ◽

2020 ◽

Author(s):

Yang Li ◽

Ji Na Zheng ◽

Chan Juan Gong ◽

Keng Fu Lan ◽

Yu Qing Shen ◽

...

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Profile Data ◽

Immune Microenvironment ◽

Normal Tissues ◽

Cerna Network ◽

Inflammatory Damage ◽

Competing Endogenous Rnas ◽

Immune Related Genes ◽

Important Significance

Abstract Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631.Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis.Results: In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003).Conclusions: Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

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Development of An Immunogenomic Landscape For The Competing Endogenous RNAs Network of Peri-Implantitis

10.21203/rs.3.rs-32312/v1 ◽

2020 ◽

Author(s):

Yang Li ◽

Ji-Na Zheng ◽

Chan-Juan Gong ◽

Keng-Fu Lan ◽

XiaoJun Ding

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Noncoding Rnas ◽

Profile Data ◽

Immune Microenvironment ◽

Normal Tissues ◽

Cerna Network ◽

Inflammatory Damage ◽

Competing Endogenous Rnas ◽

Important Significance

Abstract Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631.Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis.Results: In the analysis, the corresponding lncRNAs, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network constructed and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, which needs to be further proved by later experiments. Conclusions: Through immune-related ceRNA network, IRGs and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.One-sentences summary: GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis.

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Development of an immunogenomic landscape for the competing endogenous RNAs network of peri-implantitis

10.21203/rs.3.rs-32312/v2 ◽

2020 ◽

Author(s):

Yang Li ◽

Ji-Na Zheng ◽

Chan-Juan Gong ◽

Keng-Fu Lan ◽

Yuqing Shen Yuqing ◽

...

Keyword(s):

Immune Cells ◽

Immune Cell ◽

Profile Data ◽

Immune Microenvironment ◽

Normal Tissues ◽

Cerna Network ◽

Inflammatory Damage ◽

Competing Endogenous Rnas ◽

Immune Related Genes ◽

Important Significance

Abstract Background: Peri-implantitis is an inflammation that occurs around the implant, resulting in varying degrees of inflammatory damage to the soft and hard tissues. The characteristic criterion is the loss of the supporting bone in an inflammatory environment. However, the specific mechanisms and biomarkers involved in peri-implantitis remain to be further studied. Recently, competing endogenous RNAs (ceRNA) and immune microenvironment have been found to play a more important role in the inflammatory process. In our study, we analyzed the expression of immune related microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in peri-implantitis by analyzing GSE33774 and GSE57631.Methods: In this study, we explored the expression profile data of immune-related lncRNAs, miRNAs and mRNAs, and constructed immune-related ceRNA network involved in the pathogenesis of peri-implantitis. In addition, the CIBERSORT was used to evaluate the content of immune cells in normal tissues and peri-implantitis to detect the immune microenvironment of peri-implantitis.Results: In the analysis, 14 DElncRNAs, 16 DEmiRNAs, and 18 DEmRNAs were used to establish an immune related ceRNA network and the immune infiltration patterns associated with peri-implantitis was discovered. Through the mutual verification of the two datasets, we found that GSK3B and miR-1297 may have important significance in the immune microenvironment and pathogenesis of peri-implantitis and GSK3B was closely related to four types of immune cells, especially with the highest correlation with resting mast cells (P = 0.0003).Conclusions: Through immune-related ceRNA network, immune-related genes (IRGs) and immune cell infiltration can further comprehensively understand the pathogenesis of peri-implantitis, which built up an immunogenomic landscape with clinical significance for peri-implantitis.

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Tumour-infiltrating cytotoxic T lymphocytes in somatotroph pituitary neuroendocrine tumours

Endocrine ◽

10.1007/s12020-019-02145-y ◽

2019 ◽

Vol 67 (3) ◽

pp. 651-658 ◽

Cited By ~ 3

Author(s):

Donato Iacovazzo ◽

Sabrina Chiloiro ◽

Eivind Carlsen ◽

Antonio Bianchi ◽

Antonella Giampietro ◽

...

Keyword(s):

Cavernous Sinus ◽

First Generation ◽

Immune Cell ◽

Neuroendocrine Tumour ◽

Tumour Size ◽

Somatostatin Analogues ◽

Pituitary Tumours ◽

Immune Microenvironment ◽

Cavernous Sinus Invasion

Abstract Introduction Somatotroph pituitary tumours are often resistant to first-generation somatostatin analogues and can invade the surrounding structures, limiting the chances of curative surgery. Recent studies suggested that the immune microenvironment and pro-angiogenic factors can influence neuroendocrine tumour prognosis. In this study, we aimed to investigate the prognostic role of immune cell-specific markers and endocan, a proteoglycan involved in neoangiogenesis and cell adhesion, in a cohort of acromegaly patients who underwent pituitary surgery as first-line treatment. Subjects and methods Sixty four eligible subjects were identified. CD4+, CD8+ and CD68+ cells and endocan expression were evaluated by immunohistochemistry and results correlated with clinical and neuroradiological findings. Responsiveness to somatostatin analogues was assessed in patients with persistent disease following surgery. Results The number of CD8+ lymphocytes was significantly lower in tumours with cavernous sinus invasion (median 0.2/HPF, IQR: 2.2) compared with those without cavernous sinus invasion (median 2.4/HPF, IQR: 2.3; P = 0.04). Tumours resistant to first-generation somatostatin analogues had lower CD8+ lymphocytes (median 1/HPF, IQR: 2.4) compared with responders (median 2.4/HPF, IQR: 2.9; P = 0.005). CD4+ lymphocytes were observed sporadically. The number of CD68+ macrophages and the endothelial or tumour cell endocan expression did not differ based on tumour size, cavernous sinus invasion or treatment responsiveness. Conclusions Our study suggests that a lower number of CD8+ lymphocytes is associated with cavernous sinus invasion and resistance to treatment with first-generation somatostatin analogues in acromegaly patients. These results highlight a potential role of the tumour immune microenvironment in determining the prognosis of somatotroph pituitary tumours.

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Utilization of redox modulating small molecules that selectively act as pro-oxidants in cancer cells to open a therapeutic window for improving cancer therapy

Redox Biology ◽

10.1016/j.redox.2021.101864 ◽

2021 ◽

pp. 101864

Author(s):

M.S. Petronek ◽

J.M. Stolwijk ◽

S.D. Murray ◽

E.J. Steinbach ◽

Y. Zakharia ◽

...

Keyword(s):

Cancer Therapy ◽

Small Molecules ◽

Cancer Cells ◽

Therapeutic Window

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747 Evaluation of immune microenvironment of primary lung cancer and synchronous liver metastasis with multispectral imaging system

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-sitc2020.0747 ◽

2020 ◽

Vol 8 (Suppl 3) ◽

pp. A795-A795

Author(s):

Hyeonbin Cho ◽

Jae-Hwan Kim ◽

Ji-Hyun Kim

Keyword(s):

T Cells ◽

Liver Metastasis ◽

Multispectral Imaging ◽

Immune Cell ◽

Imaging System ◽

Cytotoxic T Cells ◽

Primary Lung Cancer ◽

Helper T Cells ◽

Synchronous Liver Metastasis ◽

Immune Microenvironment

BackgroundCancer immunotherapy (CIT) has substantially improved the survival of cancer patients. However, according to recent studies, liver metastasis was reported to predict worse outcomes for CIT. The main objective of the study is to evaluate the differences in the immune microenvironment (IME) between the primary lung cancer (PL) and synchronous liver metastasis (LM) using a multispectral imaging system.MethodsSix immune markers (CD4, CD8, CTLA-4, granzyme B (GZB), Foxp3 and PD-L1) were analyzed using a multiplex IHC system and inForm program (Akoya) on paired lung-liver samples of 10 patients. Cells were categorized into tumor nest and stroma, and cell counts per unit area were measured for comparison.ResultsThe number of tumor-infiltrating cytotoxic T cells (TIL) in PL (262.5 cells/mm2) was higher than that of LM (113.3 cells/mm2). Additionally, the ratio between the number of TIL and non-TIL was greater in PL (0.31) compared to that of LM (0.26). A similar trend appeared for Helper T cells and regulatory T cells (Treg), as PL consisted of higher numbers of T cells (791.8 Helper T cells/mm2, 195.7 Treg/mm2) than LM (626.3 Helper T cells/mm2, 121.3 Treg/mm2). However, cytotoxic T cells exhibiting GZB+ and CTLA-4- were fewer in PL (140.2 cells/mm2) than in LM (203.3 cells/mm2), and the ratio is 0.69. The mean number of GZB+ TIL in PL (32.5 cells/mm2) was lower than in LM (35.3 cells/mm2), and their proportions among total TIL counts were 0.12 and 0.31, respectively. In PL, GZB+: GZB- ratio is 0.16 while the ratio is 1.91 for LM. A fewer number of TILs exhibiting GZB suggests that PL has lower efficiency in immune response than LM. Another crucial checkpoint receptor that inhibits immune response, CTLA-4, was more prevalent in PL, with CTLA-4+: CTLA-4- ratio in Treg being 0.36 in PL, compared to 0.11 in LM. The tumor proportion score (TPS) of PD-L1 was higher in PL than LM (40.0 vs. 6.6).ConclusionsIn our study, we showed the differences in the numbers of TIL or regulatory T cells and expressions of immune checkpoint receptors (PD-L1, CTLA-4), which significantly influence outcomes for CIT. The study is ongoing to confirm different IME between the PL and LM groups in a larger tumor cohort.ReferencesPeng, Jianhong, et al., Immune Cell Infiltration in the Microenvironment of Liver Oligometastasis from Colorectal Cancer: Intratumoural CD8/CD3 Ratio Is a Valuable Prognostic Index for Patients Undergoing Liver Metastasectomy. Cancers 2019 Dec; 11(12): 1922. https://doi.org/10.3390/cancers11121922Tumeh, Paul C., et al., Liver Metastasis and treatment outcome with Anti-PD-1 monoclonal antibody in patients with melanoma and NSCLC. Cancer Immunol Res 2017 May; 5(5): 417–424. doi: 10.1158/2326-6066.CIR-16-0325Parra, E.R., Immune Cell Profiling in Cancer Using Multiplex Immunofluorescence and Digital Analysis Approaches; Streckfus, C.F., Ed.; IntechOpen: London, UK, 2018; pp. 1–13. doi: 10.5772/intechopen.80380Ribas, A., Hu-Lieskovan, S., What does PD-L1 positive or negative mean?. The Journal of Experimental Medicine 2016;213(13):2835–2840. https://doi.org/10.1084/jem.20161462

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Autophagic Markers in Chordomas: Immunohistochemical Analysis and Comparison with the Immune Microenvironment of Chordoma Tissues

Cancers ◽

10.3390/cancers13092169 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2169

Author(s):

Georgia Karpathiou ◽

Maroa Dridi ◽

Lila Krebs-Drouot ◽

François Vassal ◽

Emmanuel Jouanneau ◽

...

Keyword(s):

Tumor Cell ◽

Immune Cells ◽

Immune Cell ◽

Positive Association ◽

Immunohistochemical Analysis ◽

Vascular Density ◽

Immune Microenvironment ◽

Significant Positive Association ◽

Sequestosome 1 ◽

Cell Expression

Chordomas are notably resistant to chemotherapy. One of the cytoprotective mechanisms implicated in chemoresistance is autophagy. There are indirect data that autophagy could be implicated in chordomas, but its presence has not been studied in chordoma tissues. Sixty-one (61) chordomas were immunohistochemically studied for autophagic markers and their expression was compared with the expression in notochords, clinicopathological data, as well as the tumor immune microenvironment. All chordomas strongly and diffusely expressed cytoplasmic p62 (sequestosome 1, SQSTM1/p62), whereas 16 (26.2%) tumors also showed nuclear p62 expression. LC3B (Microtubule-associated protein 1A/1B-light chain 3B) tumor cell expression was found in 44 (72.1%) tumors. Autophagy-related 16‑like 1 (ATG16L1) was also expressed by most tumors. All tumors expressed mannose-6-phosphate/insulin-like growth factor 2 receptor (M6PR/IGF2R). LC3B tumor cell expression was negatively associated with tumor size, while no other parameters, such as age, sex, localization, or survival, were associated with the immunohistochemical factors studied. LC3B immune cell expression showed a significant positive association with programmed death-ligand 1 (PD-L1)+ immune cells and with a higher vascular density. ATG16L1 expression was also positively associated with higher vascular density. Notochords (n = 5) showed different immunostaining with a very weak LC3B and M6PR expression, and no p62 expression. In contrast to normal notochords, autophagic factors such as LC3B and ATG16L1 are often present in chordomas, associated with a strong and diffuse expression of p62, suggesting a blocked autophagic flow. Furthermore, PD-L1+ immune cells also express LC3B, suggesting the need for further investigations between autophagy and the immune microenvironment.

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Comprehensive Analysis of ESRRA in Endometrial Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821992083 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199208

Author(s):

Shufang Wang ◽

Xinlong Huo

Keyword(s):

Endometrial Cancer ◽

Protein Expression ◽

Immune Cell ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Operating Characteristics ◽

Protein Expression Level ◽

Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

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Pan-cancer characterization of lncRNA modifiers of immune microenvironment reveals clinically distinct de novo tumor subtypes

npj Genomic Medicine ◽

10.1038/s41525-021-00215-7 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Zicheng Zhang ◽

Congcong Yan ◽

Ke Li ◽

Siqi Bao ◽

Lei Li ◽

...

Keyword(s):

Noncoding Rna ◽

Immune Cell ◽

De Novo ◽

Solid Cancer ◽

Immune Microenvironment ◽

Cancer Subtypes ◽

Tumor Subtypes ◽

Cancer Immunity ◽

Systems Immunology ◽

Pan Cancer

AbstractThe emerging field of long noncoding RNA (lncRNA)-immunity has provided a new perspective on cancer immunity and immunotherapies. The lncRNA modifiers of infiltrating immune cells in the tumor immune microenvironment (TIME) and their impact on tumor behavior and disease prognosis remain largely uncharacterized. In the present study, a systems immunology framework integrating the noncoding transcriptome and immunogenomics profiles of 9549 tumor samples across 30 solid cancer types was used, and 36 lncRNAs were identified as modifier candidates underlying immune cell infiltration in the TIME at the pan-cancer level. These TIME lncRNA modifiers (TIL-lncRNAs) were able to subclassify various tumors into three de novo pan-cancer subtypes characterized by distinct immunological features, biological behaviors, and disease prognoses. Finally, a TIL-lncRNA-derived immune state index (TISI) that was reflective of immunological and oncogenic states but also predictive of patients’ prognosis was proposed. Furthermore, the TISI provided additional prognostic value for existing tumor immunological and molecular subtypes. By applying the TISI to tumors from different clinical immunotherapy cohorts, the TISI was found to be significantly negatively correlated with immune-checkpoint genes and to have the ability to predict the effectiveness of immunotherapy. In conclusion, the present study provided comprehensive resources and insights for future functional and mechanistic studies on lncRNA-mediated cancer immunity and highlighted the potential of the clinical application of lncRNA-based immunotherapeutic strategies in precision immunotherapy.

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