Compactness measures of tumor infiltrating lymphocytes in lung adenocarcinoma are associated with overall patient survival and immune scores

2020 ◽  
Author(s):  
Ruiwen Ding ◽  
Prateek Prasanna ◽  
Germán Corredor ◽  
Cheng Lu ◽  
Priya Velu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Patient Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Infiltrating Lymphocytes

scholarly journals Expression of Immune Checkpoint Regulators IDO, VISTA, LAG3, and TIM3 in Resected Pancreatic Ductal Adenocarcinoma

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2689
Author(s):  
Felix Popp ◽  
Ingracia Capino ◽  
Joana Bartels ◽  
Alexander Damanakis ◽  
Jiahui Li ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immune Checkpoint ◽  
Patient Survival ◽  
Checkpoint Inhibitors ◽  
Tumor Infiltrating Lymphocytes ◽  
Ductal Adenocarcinoma ◽  
Lymph Node Status ◽  
Clinicopathologic Parameters ◽  
Survival Differences ◽  
Infiltrating Lymphocytes

Pancreatic cancer features elaborate mechanisms of immune evasion. The potential of new immune molecules was explored to restore the antitumor immune response. If these immune molecules are associated with poor survival, specific drugs could take effect. Here, we analyze the expression of VISTA, LAG3, IDO, and TIM3 on tumor-infiltrating lymphocytes (TILs) and its impact on patient survival. We analyzed 153 pancreatic cancer patients from the prospectively managed database of the multicentered PANCALYZE study. Immunohistochemistry on a tissue microarray assessed VISTA, LAG3, IDO, and TIM3 expression of TILs from the patients undergoing primary resection. Complementarily, we analyzed publicly available transcriptomic data (n = 903). Successful completion of chemotherapy, and lymph node status were independent predictors of survival in the multivariate analysis of the clinicopathologic parameters. Fifteen tumors were exclusively VISTA-positive, thirteen tumors expressed VISTA together with TIM3, and ten tumors expressed VISTA together with IDO. Patients featuring tumors with high numbers of IDO-positive TILs had better patient survival (p = 0.037). VISTA, LAG3, and TIM3 expression did not correlate with survival. The analysis of publicly available data did not show survival differences. Tumors rarely co-express more than two immune molecules at the same time, and VISTA is most frequently co-expressed. Although IDO generally inhibits T-cell proliferation, a high expression of IDO was associated with improved survival. We expect immune checkpoint inhibitors against VISTA, LAG3, and TIM3 to be inefficient in a clinical application.

scholarly journals Immune checkpoint markers in gastroenteropancreatic neuroendocrine neoplasia

2019 ◽  
Vol 26 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Florian Bösch ◽  
Katharina Brüwer ◽  
Annelore Altendorf-Hofmann ◽  
Christoph J Auernhammer ◽  
Christine Spitzweg ◽  
...  
Keyword(s):  
Patient Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cell Surface Receptor ◽  
Clinicopathological Parameters ◽  
Term Survival ◽  
Programmed Death ◽  
Promising Therapeutic Approach ◽  
Surface Receptor ◽  
Programmed Death 1 ◽  
Infiltrating Lymphocytes

Cancer immunotherapy has evolved major breakthroughs in the last years. The cell-surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), have been detected in various cancer types. However, the analysis on gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor-infiltrating lymphocytes (TILs). On protein level, we examined TILs, PD-1 and PD-L1 expression in tumor tissue of 244 GEP-NENs using immunohistochemistry. Expression levels were correlated with clinicopathological parameters including long-term survival in an observational study. In total, 244 patients could be included. Most of the patients had a NEN of the small intestine (52.5%) or the pancreas (29.5%). All tumors could be graded by their morphology and Ki67 index, with 57.8% G1, 34% G2 and 8.2% G3 tumors. High TILs (19.6%) and high PD-1 (16.1%) expression showed a significant correlation with shorter patient survival (P < 0.05) and with a higher grading. Furthermore, expression of PD-L1 (8.7%) showed a trend to shorter patient survival. High TILs and PD-1 expression are significantly associated with shorter patient survival and higher grading in GEP-NENs. PD-L1 expression showed a trend to shorter patient survival. Immunotherapy might be a promising therapeutic approach in GEP-NENs especially in tumors with high TILs.

scholarly journals AURKA and FAM83A are prognostic biomarkers and correlated with Tumor-infiltrating Lymphocytes in smoking related Lung Adenocarcinoma

2021 ◽  
Vol 12 (6) ◽  
pp. 1742-1754
Author(s):  
Mengyu Zhang ◽  
Chen Huo ◽  
Yingxiao Jiang ◽  
Jianyu Liu ◽  
Yican Yang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Biomarkers ◽  
Infiltrating Lymphocytes

scholarly journals High expression of PD-L1 Predicts Worse Overall Survival in the Cavitary Lung Adenocarcinoma

2020 ◽  
Author(s):  
Jiangyong Liu ◽  
Mingming Gu ◽  
Yang Xue ◽  
Yong Ren ◽  
Wencai Huang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Prognostic Significance ◽  
Tumor Infiltrating Lymphocytes ◽  
Good Prognosis ◽  
High Expression ◽  
Quantitative Immunofluorescence ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

Abstract Objective Solitary cavitary lung cancer is one of the rare types of lung cancer. Generally, the relationship between cavitary lung adenocarcinoma and immunotherapy remains unknown. We aimed to assess programmed cell death ligand-1(PD-L1) expression and CD8-positive (CD8+) tumor infiltrating lymphocytes (TILs) density, and evaluate their prognostic significance of patients with cavitary lung adenocarcinoma (LUAD). Methods 65 patients diagnosed as solitary cavitary LUAD were included in this study, 30 cases of noncavitary LUAD patients were collected as controls, and their specimens from surgery or biopsy were obtained. Expression of PD-L1 protein and CD8+ TILs were detected by traditional immunohistochemistry and multiplex quantitative immunofluorescence technology. The correlations of PD-L1 expression and clinicopathological features, including overall survival in cavitary LUAD patients was evaluated based on the follow-up data. Results Overexpression of PD-L1 protein was detected in the tumor tissues of cavitary LUAD patients compared to the noncavitary LUAD controls. PD-L1 expression level was significantly related to the lymph node (P = 0.001), TNM stage (P = 0.024), and CD8+ TIL status (rs= -0.272, P = 0.025). High PD-L1 expression predicted high mortality rate (P < 0.001), but CD8+ TIL group showed better survival in cavitary LUAD patients (P = 0.011). This phenotype with high PD-L1 expression and low CD8 + TIL predicted poorer overall survival of the patients with cavitary LUAD, compared to the other phenotypes. Moreover, CD8+ TIL was an independent good prognosis factor. Conclusion We firstly demonstrated that PD-L1 is upregulated in the cavitary LUAD patients, and high expression of PD-L1 negatively correlated with CD8 T cell infiltrating status. High PD-L1 expression and low CD8 + TIL can predict poorer overall survival of the patients with cavitary LUAD.

scholarly journals Development and Validation of a Prognostic Autophagy-Related Gene Pair Index Related to Tumor-Infiltrating Lymphocytes in Early-Stage Lung Adenocarcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Zi-Hao Wang ◽  
Yu Li ◽  
Pei Zhang ◽  
Xuan Xiang ◽  
Xiao-Shan Wei ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Gene Pair ◽  
Early Stage ◽  
Tumor Infiltrating Lymphocytes ◽  
Related Gene ◽  
Tumor Immune Escape ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Infiltrating Lymphocytes

The role of autophagy in lung cancer is context-dependent and complex. Recent studies have reported the important role of autophagy in tumor immune escape. However, the association between autophagy and tumor-infiltrating lymphocytes (TILs) in early-stage lung adenocarcinoma (LUAD) remains unclear. In this study, we aimed to develop and validate the autophagy-related gene pair index (ATGPI) and autophagy clinical prognostic index (ACPI) in multiple LUAD cohorts, including The Cancer Genome Atlas (TCGA) cohort, Gene Expression Omnibus cohorts, and one cohort from Union Hospital, Wuhan (UH cohort), using a Cox proportional hazards regression model with the least absolute shrinkage and selection operator. Multivariate Cox regression analysis demonstrated that there was a significant difference in overall survival (OS) between patients with high and low ATGPI in the testing [hazard ratio (HR) = 1.97; P &lt; 0.001] and TCGA validation (HR = 2.25; P &lt; 0.001) cohorts. Time-dependent receiver operating characteristic curve analysis was also performed. We found that high ATGPI could accurately identify patients with early-stage LUAD with shorter OS, with the areas under the curve of 0.703 and 0.676 in the testing and TCGA validation cohorts, respectively. Concordance index (C-index) was used to evaluate the efficiency of ATGPI and ACPI. The C-index of ACPI was higher than that of ATGPI in the testing (0.71 vs. 0.66; P &lt; 0.001), TCGA validation (0.69 vs. 0.65; P = 0.028), and UH (0.80 vs. 0.70; P = 0.015) cohorts. TIL analysis demonstrated that the proportions of tumor-infiltrating CD4+ T cells were lower in the high-ATGPI group than in the low-ATGPI group in both the TCGA validation and UH cohorts. These results indicate the potential clinical use of ATG signatures which are associated with TILs, in identifying patients with early-stage LUAD with different OS.

Evaluation of tumor-infiltrating lymphocytes using routine H&E slides predicts patient survival in resected non–small cell lung cancer

2018 ◽  
Vol 79 ◽  
pp. 188-198 ◽  
Author(s):  
Mehrdad Rakaee ◽  
Thomas K. Kilvaer ◽  
Stig Manfred Dalen ◽  
Elin Richardsen ◽  
Erna-Elise Paulsen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Patient Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Small Cell ◽  
Small Cell Lung ◽  
Infiltrating Lymphocytes
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