scholarly journals The Prognostic Landscape of Tumor-Infiltrating Immune Cells and Immune Checkpoints in Glioblastoma

2019 ◽  
Vol 18 ◽  
pp. 153303381986994 ◽  
Author(s):  
Shiman Wu ◽  
Wenli Yang ◽  
Hua Zhang ◽  
Yan Ren ◽  
Ziwei Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Immune Checkpoint ◽  
Immunohistochemical Analysis ◽  
Response To Therapy ◽  
Expression Level ◽  
Immune Checkpoints ◽  
Tumor Escape ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Memory Cd4 T Cells

Tumor-infiltrating immune cells are part of a complex microenvironment and associated with improved clinical outcomes in a broad range of tumor types. However, a detailed map for the prognostic landscape of tumor-infiltrating immune cells and immune checkpoint modulators in glioblastoma is still lacking. Here, with the web-accessible resource, The Cancer Immunome Archive, 28 types of both adaptive and innate tumor-infiltrating immune cells were characterized in glioblastoma. Tumors lacking central memory CD4 T cells or natural killer cells were associated with better prognosis in glioblastoma, as verified by immunohistochemical analysis. Moreover, Kaplan-Meier analysis for a total of 71 key immune checkpoint molecules revealed that the expression level of inducible T cell costimulators, tumor necrosis factor superfamily member 14, and UL16 binding protein 1 were negatively correlated with the clinical outcome of patients with glioblastoma. In addition, there was a significant difference between nontumor and glioblastoma samples of several immune checkpoint modulators based on the expression level of their corresponding gene. Collectively, the annotation of tumor-infiltrating immune cells and immune checkpoint modulators in glioblastoma provides a valuable resource for identifying their involvement in tumor escape mechanisms and response to therapy.

scholarly journals From Oncogenic Signaling Pathways to Single-Cell Sequencing of Immune Cells: Changing the Landscape of Cancer Immunotherapy

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2278
Author(s):  
Afshin Derakhshani ◽  
Zeinab Rostami ◽  
Hossein Safarpour ◽  
Mahdi Abdoli Shadbad ◽  
Niloufar Sadat Nourbakhsh ◽  
...  
Keyword(s):  
Single Cell ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cancer Development ◽  
Immune Checkpoints ◽  
Single Cell Sequencing ◽  
Increased Risk

Over the past decade, there have been remarkable advances in understanding the signaling pathways involved in cancer development. It is well-established that cancer is caused by the dysregulation of cellular pathways involved in proliferation, cell cycle, apoptosis, cell metabolism, migration, cell polarity, and differentiation. Besides, growing evidence indicates that extracellular matrix signaling, cell surface proteoglycans, and angiogenesis can contribute to cancer development. Given the genetic instability and vast intra-tumoral heterogeneity revealed by the single-cell sequencing of tumoral cells, the current approaches cannot eliminate the mutating cancer cells. Besides, the polyclonal expansion of tumor-infiltrated lymphocytes in response to tumoral neoantigens cannot elicit anti-tumoral immune responses due to the immunosuppressive tumor microenvironment. Nevertheless, the data from the single-cell sequencing of immune cells can provide valuable insights regarding the expression of inhibitory immune checkpoints/related signaling factors in immune cells, which can be used to select immune checkpoint inhibitors and adjust their dosage. Indeed, the integration of the data obtained from the single-cell sequencing of immune cells with immune checkpoint inhibitors can increase the response rate of immune checkpoint inhibitors, decrease the immune-related adverse events, and facilitate tumoral cell elimination. This study aims to review key pathways involved in tumor development and shed light on single-cell sequencing. It also intends to address the shortcomings of immune checkpoint inhibitors, i.e., their varied response rates among cancer patients and increased risk of autoimmunity development, via applying the data from the single-cell sequencing of immune cells.

scholarly journals The Immune Landscape of Thyroid Cancer in the Context of Immune Checkpoint Inhibition

2019 ◽  
Vol 20 (16) ◽  
pp. 3934 ◽  
Author(s):  
Gilda Varricchi ◽  
Stefania Loffredo ◽  
Giancarlo Marone ◽  
Luca Modestino ◽  
Poupak Fallahi ◽  
...  
Keyword(s):  
Cell Death ◽  
Thyroid Cancer ◽  
Programmed Cell Death ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Lymphatic Vessels ◽  
The United States ◽  
Immune Checkpoints ◽  
Antitumor Effects

Immune cells play critical roles in tumor prevention as well as initiation and progression. However, immune-resistant cancer cells can evade the immune system and proceed to form tumors. The normal microenvironment (immune cells, fibroblasts, blood and lymphatic vessels, and interstitial extracellular matrix (ECM)) maintains tissue homeostasis and prevents tumor initiation. Inflammatory mediators, reactive oxygen species, cytokines, and chemokines from an altered microenvironment promote tumor growth. During the last decade, thyroid cancer, the most frequent cancer of the endocrine system, has emerged as the fifth most incident cancer in the United States (USA), and its incidence is steadily growing. Inflammation has long been associated with thyroid cancer, raising critical questions about the role of immune cells in its pathogenesis. A plethora of immune cells and their mediators are present in the thyroid cancer ecosystem. Monoclonal antibodies (mAbs) targeting immune checkpoints, such as mAbs anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA-4) and anti-programmed cell death protein-1/programmed cell death ligand-1 (anti-PD-1/PD-L1), have revolutionized the treatment of many malignancies, but they induce thyroid dysfunction in up to 10% of patients, presumably by enhancing autoimmunity. Combination strategies involving immune checkpoint inhibitors (ICIs) with tyrosine kinase (TK) or serine/threonine protein kinase B-raf (BRAF) inhibitors are showing considerable promise in the treatment of advanced thyroid cancer. This review illustrates how different immune cells contribute to thyroid cancer development and the rationale for the antitumor effects of ICIs in combination with BRAF/TK inhibitors.

scholarly journals Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract Background Breast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.Methods At first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.Results The results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC. conclusions In summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

scholarly journals Prognostic Gene Expression Signature in Patients With Distinct Glioma Grades

2021 ◽  
Vol 12 ◽  
Author(s):  
Saadia Ait Ssi ◽  
Dounia Chraa ◽  
Khadija El Azhary ◽  
Souha Sahraoui ◽  
Daniel Olive ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Cells ◽  
Cox Regression ◽  
Gene Expression Signature ◽  
The Cancer Genome Atlas ◽  
Immune Checkpoints ◽  
Tumor Escape ◽  
Cox Regression Analysis ◽  
Patient Prognosis ◽  
Cluster 2

BackgroundGlioma is the most common type of primary brain tumor in adults. Patients with the most malignant form have an overall survival time of <16 months. Although considerable progress has been made in defining the adapted therapeutic strategies, measures to counteract tumor escape have not kept pace, due to the developed resistance of malignant glioma. In fact, identifying the nature and role of distinct tumor-infiltrating immune cells in glioma patients would decipher potential mechanisms behind therapy failure.MethodsWe integrated into our study glioma transcriptomic datasets from the Cancer Genome Atlas (TCGA) cohort (154 GBM and 516 LGG patients). LM22 immune signature was built using CIBERSORT. Hierarchical clustering and UMAP dimensional reduction algorithms were applied to identify clusters among glioma patients either in an unsupervised or supervised way. Furthermore, differential gene expression (DGE) has been performed to unravel the top expressed genes among the identified clusters. Besides, we used the least absolute shrinkage and selection operator (LASSO) and Cox regression algorithm to set up the most valuable prognostic factor.ResultsOur study revealed, following gene enrichment analysis, the presence of two distinct groups of patients. The first group, defined as cluster 1, was characterized by the presence of immune cells known to exert efficient antitumoral immune response and was associated with better patient survival, whereas the second group, cluster 2, which exhibited a poor survival, was enriched with cells and molecules, known to set an immunosuppressive pro-tumoral microenvironment. Interestingly, we revealed that gene expression signatures were also consistent with each immune cluster function. A strong presence of activated NK cells was revealed in cluster 1. In contrast, potent immunosuppressive components such as regulatory T cells, neutrophils, and M0/M1/M2 macrophages were detected in cluster 2, where, in addition, inhibitory immune checkpoints, such as PD-1, CTLA-4, and TIM-3, were also significantly upregulated. Finally, Cox regression analysis further corroborated that tumor-infiltrating cells from cluster 2 exerted a significant impact on patient prognosis.ConclusionOur work brings to light the tight implication of immune components on glioma patient prognosis. This would contribute to potentially developing better immune-based therapeutic approaches.

scholarly journals Immune Checkpoint Expression on Immune Cells of HNSCC Patients and Modulation by Chemo- and Immunotherapy

2020 ◽  
Vol 21 (15) ◽  
pp. 5181
Author(s):  
Lisa K. Puntigam ◽  
Sandra S. Jeske ◽  
Marlies Götz ◽  
Jochen Greiner ◽  
Simon Laban ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Necrosis Factor ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Receptor ◽  
Immune Checkpoints ◽  
Healthy Donors ◽  
Necrosis Factor

Endogenous control mechanisms, including immune checkpoints and immunosuppressive cells, are exploited in the process of tumorigenesis to weaken the anti-tumor immune response. Cancer treatment by chemotherapy or immune checkpoint inhibition can lead to changes of checkpoint expression, which influences therapy success. Peripheral blood lymphocytes (PBL) and tumor-infiltrating lymphocytes (TIL) were isolated from head and neck squamous cell carcinoma (HNSCC) patients (n = 23) and compared to healthy donors (n = 23). Immune checkpoint expression (programmed cell death ligand 1 (PD-1), tumor necrosis factor receptor (TNFR)-related (GITR), CD137, tumor necrosis factor receptor superfamily member 4 (TNFRSF4) (OX40), t-cell immunoglobulin and mucin-domain containing-3 (TIM3), B- and T-lymphocyte attenuator (BTLA), lymphocyte-activation gene 3 (LAG3)) was determined on immune cells by flow cytometry. PD-L1 expression was detected on tumor tissue by immunohistochemistry. Immune cells were treated with immuno- and chemotherapeutics to investigate treatment-specific change in immune checkpoint expression, in vitro. Specific changes of immune checkpoint expression were identified on PBL and TIL of HNSCC patients compared to healthy donors. Various chemotherapeutics acted differently on the expression of immune checkpoints. Changes of checkpoint expression were significantly less pronounced on regulatory T cells compared to other lymphocyte populations. Nivolumab treatment significantly reduced the receptor PD-1 on all analyzed T cell populations, in vitro. The specific immune checkpoint expression patterns in HNSCC patients and the investigated effects of immunomodulatory agents may improve the development and efficacy of targeted immunotherapy.

scholarly journals Analysis of Intra-Tumoral Macrophages and T Cells in Non-Small Cell Lung Cancer (NSCLC) Indicates a Role for Immune Checkpoint and CD200-CD200R Interactions

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1788
Author(s):  
Anders Tøndell ◽  
Yashwanth Subbannayya ◽  
Sissel Gyrid Freim Wahl ◽  
Arnar Flatberg ◽  
Sveinung Sørhaug ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Immune Checkpoint ◽  
Expression Profiles ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Cell Immune Response ◽  
Small Cell Lung ◽  
Tumor Associated Macrophages ◽  
Cell Lung Carcinoma

Non-small cell lung carcinoma (NSCLC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related deaths. Immunotherapy with immune checkpoint inhibitors shows beneficial responses, but only in a proportion of patients. To improve immunotherapy in NSCLC, we need to map the immune checkpoints that contribute immunosuppression in NSCLC-associated immune cells and to identify novel pathways that regulate immunosuppression. Here, we investigated the gene expression profiles of intra-tumoral immune cells isolated from NSCLC patients and compared them to the expression profiles of their counterparts in adjacent healthy tissue. Transcriptome analysis was performed on macrophages, CD4+ and CD8+ T cells. The data was subjected to Gene Ontology (GO) term enrichment and weighted correlation network analysis in order to identify mediators of immunosuppression in the tumor microenvironment in NSCLC. Immune cells from NSCLC revealed a consistent differential expression of genes involved in interactions between myeloid cells and lymphocytes. We further identified several immunosuppressive molecules and pathways that may be activated in tumor-associated macrophages in NSCLC. Importantly, we report novel data on immune cell expression of the newly described CD200/CD200R1 pathway, and the leukocyte immunoglobulin-like receptors (LILRs), which may represent novel innate immune checkpoints, dampening the anti-tumor T cell immune response in NSCLC. Our study substantiates the importance of tumor-associated macrophages as a mediator of immunosuppression and a promising target for immunotherapy.

scholarly journals The Heterogeneity of Infiltrating Macrophages in Metastatic Osteosarcoma and Its Correlation with Immunotherapy

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Zhanchao Wang ◽  
Huiqiao Wu ◽  
Yu Chen ◽  
Huajiang Chen ◽  
Wen Yuan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Risk Model ◽  
Disease Free Survival ◽  
Immune Checkpoints ◽  
Free Survival ◽  
Primary Osteosarcoma ◽  
Kaplan Meier ◽  
Metastatic Osteosarcoma ◽  
Related Risk ◽  
Disease Free

Background. Metastatic osteosarcoma is a common and fatal bone tumor. Several studies have found that tumor-infiltrating immune cells play pivotal roles in the progression of metastatic osteosarcoma. However, the heterogeneity of infiltrating immune cells across metastatic and primary osteosarcoma remains unclear. Methods. Immune infiltration analysis was carried out via the “ESTIMATE” and “xCell” algorithms in primary and metastatic osteosarcoma. Then, we evaluated the prognostic value of infiltrating immune cells in 85 osteosarcomas through the Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curve. Infiltrations of macrophage M1 and M2 were evaluated in metastatic osteosarcoma, as well as their correlation with immune checkpoints. Macrophage-related prognostic genes were identified through Weighted Gene Coexpression Network Analysis (WGCNA), Lasso analysis, and Random Forest algorithm. Finally, a macrophage-related risk model had been constructed and validated. Results. Macrophages, especially the macrophage M1, sparingly infiltrated in metastatic compared with the primary osteosarcoma and predicted the worse overall survival (OS) and disease-free survival (DFS). Macrophage M1 was positively correlated with immune checkpoints PDCD1, CD274 (PD-L1), PDCD1LG2, CTLA4, and TIGIT. In addition, four macrophage-related prognostic genes (IL10, VAV1, CD14, and CCL2) had been identified, and the macrophage-related risk model had been validated to be reliable for evaluating prognosis in osteosarcoma. Simultaneously, the risk score showed a strong correlation with several immune checkpoints. Conclusion. Macrophages potentially contribute to the regulation of osteosarcoma metastasis. It can be used as a candidate marker for metastatic osteosarcoma’ prognosis and immune checkpoints blockades (ICBs) therapy. We constructed a macrophage-related risk model through machine-learning, which might help us evaluate patients’ prognosis and response to ICBs therapy.

scholarly journals Immune checkpoint inhibitors in therapy of non-small cell lung cancer (a review)

2021 ◽  
Vol 23 (3) ◽  
pp. 417-424
Author(s):  
O. P. Kolesnik ◽  
V. V. Mykhailychenko
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Response To Therapy ◽  
Expression Level ◽  
Small Cell Lung

Aim. Based on scientific literature data, to evaluate the effectiveness of the use of immune checkpoint inhibitors (ICI) in the treatment of non-small cell lung cancer (NSCLC). Materials and methods. To analyze the results of clinical trials of NSCLC treatment with immune checkpoint inhibitors. Conclusions. Among the immune checkpoint inhibitors, PD-1/PD-L1 inhibitors, namely Nivolumab, Pembrolizumab and Atezolizumab, are most successful in the treatment of NSCLC. Their use significantly increases overall survival and progression-free survival with a lower profile of adverse events. They are prescribed as both second-line and first-line drugs in the NSCLC therapy. Such biomarkers as Teff gene expression level, tumor mutational load (TMB) level and interferon gamma (IFNG) mRNA expression level have also been identified. They allow to more accurately determine the group of patients who will show the best response to therapy with PD-1/ PD-L1 inhibitors.

scholarly journals Upregulated CCNE1 Correlates with Poor Prognosis, Tumor Immune Infiltration and Escape in Breast Cancer

2021 ◽  
Author(s):  
Jiaxi Feng ◽  
Yanan Hu ◽  
Dan Liu ◽  
Shanshan Wang ◽  
Mengci Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Cells ◽  
Poor Prognosis ◽  
Immune Cell ◽  
High Expression ◽  
Expression Level ◽  
Immune Cell Infiltration ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Kaplan Meier Plotter

Abstract BackgroundBreast cancer (BC) is the most common malignant tumor in women and widely known for its poor prognosis. More and more research has discovered that cyclin E1 (CCNE1) plays an important role in progression of various types of cancer. But its specific mechanism in BC progression still needs further research to explore.MethodsAt first, we determined the expression and prognostic value of CCNE1 through The Cancer Genome Atlas (TCGA) database and The Genotype-Tissue Expression (GTEx) data. Then, we predicted the upstream non-coding RNAs of CCNE1 through StarBase, GEPIA, and Kaplan-Meier plotter database. We further studied the correlation of CCNE1 expression with BC immune cell infiltration, biomarkers of immune cells and immune checkpoints expression through TIMER and GEPIA databases.ResultsThe results suggested that CCNE1 was significantly upregulated in BC and its high expression was correlated with poor prognosis in BC patients. Next, we identified long noncoding RNA (lncRNA) LINC00511 / microRNA-195-5p (miR-195-5p) / CCNE1 axis as the most potential pathway that could regulate CCNE1 expression in BC through StarBase, GEPIA, and Kaplan-Meier plotter database. Furthermore, our in-depth research discovered that CCNE1 expression level was significantly correlated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression in BC.ConclusionIn summary, high expression level of CCNE1 was significantly correlated with poor prognosis, tumor immune infiltration and escape in BC.

scholarly journals Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells

2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ma-Yan Huang ◽  
Xiao-Yun Liu ◽  
Qiong Shao ◽  
Xu Zhang ◽  
Lei Miao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Expression Patterns ◽  
Immunohistochemical Analysis ◽  
Cancer Center ◽  
Phosphoserine Phosphatase ◽  
Kaplan Meier ◽  
Dismal Prognosis ◽  
Tcga Dataset ◽  
Cox Analysis

Abstract Background Because of dismal prognosis in gastric cancer, identifying relevant prognostic factors is necessary. Phosphoserine phosphatase (PSPH) exhibits different expression patterns in many cancers and has been reported to affect the prognosis of patients with cancer. In this study, we examined the prognostic role of metabolic gene PSPH in gastric cancer based on the TCGA dataset and our hospital–based cohort cases. Methods We collected and analysed RNA-seq data of Pan-cancer and gastric cancer in the TCGA dataset and PSPH expression data obtained from immunohistochemical analysis of 243 patients with gastric cancer from Sun Yat-sen University cancer center. Further, Kaplan–Meier survival analysis and Cox analysis were used to assess the effect of PSPH on prognosis. The ESTIMATE and Cibersort algorithms were used to elucidate the relationship between PSPH and the abundance of immune cells using the TCGA dataset. Results We observed that PSPH expression displayed considerably high in gastric cancer and it was significantly associated with inferior prognosis (P = 0.043). Surprisingly, there was a significant relationship between lower immune scores and high expression of PSPH (P < 0.05). Furthermore, patients with a low amount of immune cells exhibited poor prognosis (P = 0.046). The expression of PSPH significantly increased in activated memory CD4 T cells, resting NK cells and M0 macrophages (P = 0.037, < 0.001, and 0.005, respectively). Conclusions This study highlighted that PSPH influences the prognosis of patients with gastric cancer, and this is associated with the infiltration of tumour immune cells, indicating that PSPH may be a new immune-related target for treating gastric cancer.

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