scholarly journals Prognostic value of trafficking of regulatory T cells to tumors in head and neck cancer patients.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 104-104
Author(s):  
Hyun Chang ◽  
Hyun Jun Hong ◽  
Yongho Kim
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Head And Neck ◽  
Prognostic Value ◽  
Cox Regression ◽  
Progression Free Survival ◽  
The Cancer Genome Atlas ◽  
Significant Prognostic Factor ◽  
Immune Activity ◽  
Prognostic Effect

104 Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.

scholarly journals Identification of Novel Biomarkers for Predicting Prognosis and Immunotherapy Response in Head and Neck Squamous Cell Carcinoma Based on ceRNA Network and Immune Infiltration Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-42
Author(s):  
Ya Guo ◽  
Wei Kang Pan ◽  
Zhong Wei Wang ◽  
Wang Hui Su ◽  
Kun Xu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Regulatory T Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Cerna Network

Objectives. Patients with head and neck squamous cell carcinoma (HNSCC) have poor prognosis and show poor responses to immune checkpoint (IC) inhibitor (ICI) therapy. Competing endogenous RNA (ceRNA) networks, tumor-infiltrating immune cells (TIICs), and ICIs may influence tumor prognosis and response rates to ICI therapy. This study is aimed at identifying prognostic and IC-related biomarkers and key TIIC signatures to improve prognosis and ICI therapy response in HNSCC patients. Methods and Results. Ninety-five long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and 1746 mRNAs were identified using three independent methods. We constructed a ceRNA network and estimated the proportions of 22 immune cell subtypes. Ten ceRNAs were related to prognosis according to Kaplan–Meier analysis. Two risk signatures based, respectively, on nine ceRNAs (ANLN, CFL2, ITGA5, KDELC1, KIF23, NFIA, PTX3, RELT, and TMC7) and three immune cell types (naïve B cells, neutrophils, and regulatory T cells) via univariate Cox regression, least absolute shrinkage and selection operator, and multivariate Cox regression analyses could accurately and independently predict the prognosis of HNSCC patients. Key mRNAs in the ceRNA network were significantly correlated with naïve B cells and regulatory T cells and with stage, grade, and immune and molecular subtype. Eight IC genes exhibited higher expression in tumor tissues and were correlated with eight key mRNAs in the ceRNA network in HNSCC patients with different HPV statuses according to coexpression and TIMER 2.0 analyses. Most drugs were effective in association with expression of these key signatures (ANLN, CFL2, ITGA5, KIF23, NFIA, PTX3, RELT, and TMC7) based on GSCALite analysis. The prognostic value of key biomarkers and associations between key ceRNAs and IC genes were validated using online databases. Eight key ceRNAs were confirmed to predict response to ICI in other cancers based on TIDE analysis. Conclusions. We constructed two risk signatures to accurately predict prognosis in HNSCC. Key IC-related signatures may be associated with response to ICI therapy. Combinations of ICIs with inhibitors of eight key mRNAs may improve survival outcomes of HNSCC patients.

scholarly journals Expression Profile and Prognostic Value of CXCR Family Members in Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Yiming Shen ◽  
Chongchang Zhou ◽  
Yujie Cao ◽  
Qun Li ◽  
Hongxia Deng ◽  
...  
Keyword(s):  
Head And Neck ◽  
Expression Profile ◽  
Prognostic Value ◽  
Inflammatory Responses ◽  
Receptor Gene ◽  
Family Members ◽  
Enrichment Analysis ◽  
Progression Free Survival ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas

Abstract Background: CXC chemokine receptor gene family consists of seven well-established members which are broadly involved in biological functions of various cancers. Currently, limited studies have shed light on the expression profile of CXCR family members (CXCRs), as well as their prognostic value, in head and neck squamous cells carcinoma (HNSCC). Methods: The data for this study were retrieved from the Cancer Genome Atlas database and other publicly available databases, including gene expression, methylation profiles, clinical information, immunological features and prognoses. The expression pattern and prognostic values of CXCRs were identified, and the potential mechanism underlying CXCRs function in HNSCC was investigated by gene set enrichment analysis (GSEA). Results: CXCRs were differentially expressed in HNSCC. As shown by Kaplan Meier analysis, high CXCR3-6 expression was significantly associated with better prognostic outcomes of HNSCC patients, including overall survival and progression-free survival. According to the results of univariate and multivariate Cox proportional risk regression analysis, it was demonstrated that upregulation of CXCR3-6 was an independent factor for better prognosis, while the two other clinical features, age and stage, were factors for worse prognosis. A significant positive correlation between CXCR3-6 and tumor-infiltrated immune cells was revealed by results from Tumor Immune Estimation Resource and CIBERSORT analysis database. The main involvement of CXCRs in immune and inflammatory responses was further confirmed by GSEA. Conclusions: Overall, this study provided a rationale for targeting CXCRs as a promising therapeutic strategy of HNSCC.

scholarly journals Regulatory T cells and their prognostic value for patients with squamous cell carcinoma of the head and neck

2009 ◽  
Vol 14 (1-2) ◽  
pp. 426-433 ◽  
Author(s):  
Jan Boucek ◽  
Tomas Mrkvan ◽  
Martin Chovanec ◽  
Martin Kuchar ◽  
Jaroslav Betka ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Regulatory T Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value

scholarly journals Identification of Three Autophagy-Related Long Non-Coding RNAs as a Novel Head and Neck Squamous Cell Carcinoma Prognostic Signature

2021 ◽  
Vol 10 ◽  
Author(s):  
Ya Guo ◽  
Peng Tao Yang ◽  
Zhong Wei Wang ◽  
Kun Xu ◽  
Wei Hua Kou ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Cox Regression ◽  
Neck Squamous Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cox Regression Analysis ◽  
Non Coding Rnas

Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis. Considerable evidence indicates that autophagy and non-coding RNA play essential roles in the biological processes involved in cancers, but associations between autophagy-related long non-coding RNAs (lncRNAs) and HNSCC remain unclear. In the present study, HNSCC RNA sequences and autophagy-related gene data were extracted from The Cancer Genome Atlas database and the Human Autophagy Database. A total of 1,153 autophagy-related lncRNAs were selected via calculating Pearson’s correlation coefficient. Three prognosis-related autophagy lncRNAs were identified via univariate Cox regression, least absolute shrinkage and selection operator analysis, and multivariate Cox regression analysis. We also constructed a prognostic model based on these autophagy-related lncRNAs and evaluated its ability to accurately and independently predict the prognosis of HNSCC patients. The area under the curve (AUC) was 0.864 (3-year) and 0.836 (5-year), and our model can independently predict the prognosis of HNSCC. The prognostic value of the three autophagy lncRNAs was confirmed via analysis of samples from five databases. To further identify the functions of the three lncRNAs, a co-expression network was constructed and pathway analysis was performed. In that analysis the lncRNAs were correlated with 189 related genes and 20 autophagy-related genes, and these lncRNAs mainly involved homologous recombination, the Fanconi anemia pathway, the autophagy-related pathway, and immune-related pathways. In addition, we validated the expression levels of three lncRNAs and autophagy markers (ATG12, BECN1, and MAP1LC3B) based on TIMER, Oncomine, and HPA database analysis. Our results indicated that TTTY15 was increased in HPV positive and HPV negative HNSCC patients, and three autophagy markers were up-regulated in all HNSCCC patients. Lastly, association between three lncRNAs and autophagy markers was performed, and our results showed that TTTY15 and MIF-AS1 were associated with autophagy markers. Collectively, these results suggested that three autophagy-related lncRNAs have prognostic value in HNSCC patients.

scholarly journals Alterations in regulatory T cells and immune checkpoint molecules in pancreatic cancer patients receiving FOLFIRINOX or gemcitabine plus nab-paclitaxel

2021 ◽  
Author(s):  
L. Sams ◽  
S. Kruger ◽  
V. Heinemann ◽  
D. Bararia ◽  
S. Haebe ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Immune Checkpoints ◽  
Prognostic Information ◽  
Peripheral Blood Mononuclear

Abstract Purpose This pilot study aimed on generating insight on alterations in circulating immune cells during the use of FOLFIRINOX and gemcitabine/nab-paclitaxel in pancreatic ductal adenocarcinoma (PDAC). Patients and methods Peripheral blood mononuclear cells were isolated before and 30 days after initiation of chemotherapy from 20 patients with advanced PDAC. Regulatory T cells (FoxP3+) and immune checkpoints (PD-1 and TIM-3) were analyzed by flow cytometry and immunological changes were correlated with clinical outcome. Results Heterogeneous changes during chemotherapy were observed in circulating T-cell subpopulations with a pronounced effect on PD-1+ CD4+/CD8+ T cells. An increase in FoxP3+ or PD-1+ T cells had no significant effect on survival. An increase in TIM3+/CD8+ (but not TIM3+/CD4+) T cells was associated with a significant inferior outcome: median progression-free survival in the subgroup with an increase of TIM-3+/CD8+ T cells was 6.0 compared to 14.0 months in patients with a decrease/no change (p = 0.026); corresponding median overall survival was 13.0 and 20.0 months (p = 0.011), respectively. Conclusions Chemotherapy with FOLFIRNOX or gemcitabine/nab-paclitaxel induces variable changes in circulating T-cell populations that may provide prognostic information in PDAC.

scholarly journals Tumor hypoxia is associated with resistance to PD-1 blockade in squamous cell carcinoma of the head and neck

2021 ◽  
Vol 9 (5) ◽  
pp. e002088
Author(s):  
Dan P Zandberg ◽  
Ashley V Menk ◽  
Maria Velez ◽  
Daniel Normolle ◽  
Kristin DePeaux ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Cd8 T Cells ◽  
Oxidative Metabolism ◽  
Cox Regression ◽  
Tumor Hypoxia ◽  
Parental Line

The majority of patients with recurrent/metastatic squamous cell carcinoma of the head and neck (HNSCC) (R/M) do not benefit from anti-PD-1 therapy. Hypoxia induced immunosuppression may be a barrier to immunotherapy. Therefore, we examined the metabolic effect of anti-PD-1 therapy in a murine MEER HNSCC model as well as intratumoral hypoxia in R/M patients. In order to characterize the tumor microenvironment in PD-1 resistance, a MEER cell line was created from the parental line that are completely resistant to anti-PD-1. These cell lines were then metabolically profiled using seahorse technology and injected into C57/BL6 mice. After tumor growth, mice were pulsed with pimonidazole and immunofluorescent imaging was performed to analyze hypoxia and T cell infiltration. To validate the preclinical results, we analyzed tissues from R/M patients (n=36) treated with anti-PD-1 mAb, via immunofluorescent imaging for number of CD8+ T cells (CD8), Tregs and the percent area (CAIX) and mean intensity (I) of carbonic anhydrase IX in tumor. We analyzed disease control rate (DCR), progression free survival (PFS), and overall survival (OS) using proportional odds and proportional hazards (Cox) regression. We found that anti-PD-1 resistant MEER has significantly higher oxidative metabolism, while there was no difference in glycolytic metabolism. Intratumoral hypoxia was significantly increased and CD8+ T cells decreased in anti-PD-1 resistant tumors compared with parental tumors in the same mouse. In R/M patients, lower tumor hypoxia by CAIX/I was significantly associated with DCR (p=0.007), PFS, and OS, and independently associated with response (p=0.028) and PFS (p=0.04) in a multivariate model including other significant immune factors. During PD-1 resistance, tumor cells developed increased oxidative metabolism leading to increased intratumoral hypoxia and a decrease in CD8+ T cells. Lower tumor hypoxia was independently associated with increased efficacy of anti-PD-1 therapy in patients with R/M HNSCC. To our knowledge this is the first analysis of the effect of hypoxia in this patient population and highlights its importance not only as a predictive biomarker but also as a potential target for therapeutic intervention.

Prognostic value of peripheral naive CD8+ T cells in oligometastatic non-small-cell lung cancer

2021 ◽  
Author(s):  
Xin Zhao ◽  
Yan Zhang ◽  
Zhenlin Gao ◽  
Yaguang Han
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
T Cells ◽  
Small Cell Lung Cancer ◽  
Immune Cells ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival

Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.

Immune Characteristics-Related Typing of Colorectal Cancer and the Establishment of 14-Gene Prognostic Model

2021 ◽  
Author(s):  
Jianxing Ma ◽  
Chen Wang
Keyword(s):  
Colorectal Cancer ◽  
Risk Model ◽  
Cox Regression ◽  
Nonnegative Matrix ◽  
Test Group ◽  
Progression Free Survival ◽  
Risk Groups ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Immune Related Genes

Abstract This study is to establish NMF (nonnegative matrix factorization) typing related to the tumor microenvironment (TME) of colorectal cancer (CRC) and to construct a gene model related to prognosis to be able to more accurately estimate the prognosis of CRC patients. NMF algorithm was used to classify samples merged clinical data of differentially expressed genes (DEGs) of TCGA that are related to the TME shared in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, and survival differences between subtype groups were compared. By using createData Partition command, TCGA database samples were randomly divided into train group and test group. Then the univariate Cox analysis, Lasso regression and multivariate Cox regression models were used to obtain risk model formula, which is used to score the samples in the train group, test group and GEO database, and to divide the samples of each group into high-risk and low-risk groups, according to the median score of the train group. After that, the model was validated. Patients with CRC were divided into 2, 3, 5 subtypes respectively. The comparison of patients with overall survival (OS) and progression-free survival (PFS) showed that the method of typing with the rank set to 5 was the most statistically significant (p=0.007, p<0.001, respectively). Moreover, the model constructed containing 14 immune-related genes (PPARGC1A, CXCL11, PCOLCE2, GABRD, TRAF5, FOXD1, NXPH4, ALPK3, KCNJ11, NPR1, F2RL2, CD36, CCNF, DUSP14) can be used as an independent prognostic factor, which is superior to some previous models in terms of patient prognosis. The 5-type typing of CRC patients and the 14 immune-related genes model constructed by us can accurately estimate the prognosis of patients with CRC.

scholarly journals Ferroptosis-Related Long Non-Coding RNAs and the Roles of LASTR in Stomach Adenocarcinoma

2021 ◽  
Author(s):  
Gongjun Wang ◽  
Libin Sun ◽  
Shasha Wang ◽  
Jing Guo ◽  
Hui Li ◽  
...  
Keyword(s):  
Cox Regression ◽  
Comprehensive Evaluation ◽  
Progression Free Survival ◽  
High Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Sequencing Data ◽  
Regulatory Relationship ◽  
Data Resource ◽  
Stomach Adenocarcinoma

Abstract Background: Ferroptosis is a form of cell death involved in diverse physiological context. Increasing evidence suggests that there is a closely regulatory relationship between ferroptosis and long noncoding RNAs (lncRNAs).Method: RNA-sequencing data from The Cancer Genome Atlas (TCGA) data resource and ferroptosis-related genes from FerrDb (http://www.zhounan.org/ferrdb/) data resource were employed to select differentially expressed lncRNAs. We performed Univariate Cox regression and multivariate Cox analyses analysis on these differentially expressed lncRNAs to screen independent predictive factors. Subsequently, we established two signatures for predicting overall survival (OS) and progression-free survival (PFS). Finally, experiments were conducted to verify the roles of LASTR in gastric cancer (GC).Results: We identified 12 differentially expressed lncRNAs linked with OS and 13 associated with PFS. Kaplan-Meier(K-M) analyses exhibited that the high-risk group was related to a poor prognosis of stomach adenocarcinoma (STAD). The AUCs of the OS, as well as PFS signatures of lncRNAs were 0.734 and 0.771, respectively, indicating their excellent efficacy in predicting STAD prognosis. Our experimental results illustrated that the inhibition of LASTR inhibited tumor proliferation and migration in GC.Conclusion: This comprehensive evaluation of the ferroptosis-related lncRNA landscape in STAD unearthed novel lncRNAs related to carcinogenesis. In addition, we also experimentally confirmed the effects of LASTR on proliferation, migration and ferroptosis. These results provide potential novel targets for tumor treatment and promote personalized medicine.

scholarly journals In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Lygia Bertalha Yaegashi ◽  
Camila Machado Baldavira ◽  
Tabatha Gutierrez Prieto ◽  
Juliana Machado-Rugolo ◽  
Ana Paula Pereira Velosa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cox Regression ◽  
Cytotoxic T Cells ◽  
Small Cell ◽  
Malignant Cells ◽  
Pathological Stage ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors’ immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8+, Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers—the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III &gt; 24.89 fibers/mm². Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression &gt; 52.86 cells/mm² and CD3+ ≤ 278.5 cells/mm². We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.

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