Computational approaches for characterizing the tumor immune microenvironment

Liu, Candace C.; Steen, Chloé B.; Newman, Aaron M.

doi:10.1111/imm.13101

Cited by 32 publications

(29 citation statements)

References 162 publications

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“…Bioinformatics approaches can directly extract cell-type specific information using sophisticated computational approaches [13]. Studies of the tumor immune microenvironment increasingly involve complex datasets which mainly depend on sophisticated computational methods [14]. The bioinformatics approaches were used in our study to investigate the immune microenvironment and the genes involved in different stages of LUAD and LUSC.…”

Section: Ivyspringmentioning

confidence: 99%

Identification of the key genes and characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC)

et al. 2020

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This study aimed to investigate the key genes and immune microenvironment involved in different TNM stages of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The gene expression and clinical characteristics data were downloaded from the genomic data commons (GDC) database. After initial data processing, the characteristics of the immune microenvironment were analyzed. The differentially expressed genes (DEGs) in tumor vs. normal, and in early vs. advanced stages were screened, followed by Spearman correlation test for tumor infiltrating immune cells (TIICs) to identify immune-related genes. Finally, functional enrichment, protein-protein interaction, and survival analyses were performed. In LUAD, early stage was with higher immune scores, greater number of memory B cells and M0 macrophages compared to advanced stage. M0 and M2 macrophages, and resting memory CD4+ T cells accounted for a large proportion of TIICs in LUAD. The abundance of M0 macrophage infiltration was significantly correlated with the TNM stage and survival. In LUSC, early stage was with higher cytolytic activity and neoantigen burden compared to advanced stage. M0 and M2 macrophages, and plasma cells accounted for a large proportion of TIICs in LUSC. The abundance of resting and activated mast cells was significantly correlated with TNM stage, while resting dendritic cells, eosinophils, activated memory CD4 T cells, and mast cells were significantly correlated with prognosis. Tumor mutation burden analysis revealed that the median of variants per sample decreased from stage I to IV in LUAD, while it increased in LUSC. Further, 83 and 9 immune-related DEGs were identified in LUAD and LUSC, respectively, of which 23 genes in LUAD and 2 genes in LUSC correlated with survival. In conclusion, we identified the key genes, and characterized the tumor immune microenvironment in LUAD and LUSC which may provide therapeutic targets for the treatment of NSCLC.

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Section: Ivyspringmentioning

confidence: 99%

Identification of the key genes and characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC)

et al. 2020

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“…MIBI is compatible with formalin-fixed paraffin-embedded (FFPE) tissue samples, the foremost preservation method of solid tissue in routine clinical pathology. MIBI enables in-depth analysis of the interactions of the TIME, measuring the expression of more than 40 proteins simultaneously while preserving spatial information 26 and avoiding spectral overlap 27 and autofluorescence 28 .…”

Section: Introductionmentioning

confidence: 99%

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

Patwa

Yamashita

Jin

et al. 2021

Preprint

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Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.

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“…In recent years, the intratumoral infiltration of immune cells has attracted increasing attention as an important factor of the tumor microenvironment (TME) ( 40 , 41 ). Immunohistochemical staining was used to analyze the correlation between GLI2 expression and tumor infiltrating lymphocytes (TILs) in GBC specimens.…”

Section: Resultsmentioning

confidence: 99%

GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer

et al. 2021

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We previously reported that Hedgehog (Hh) signal was enhanced in gallbladder cancer (GBC) and was involved in the induction of malignant phenotype of GBC. In recent years, therapeutics that target Hh signaling have focused on molecules downstream of smoothened (SMO). The three transcription factors in the Hh signal pathway, glioma-associated oncogene homolog 1 (GLI1), GLI2, and GLI3, function downstream of SMO, but their biological role in GBC remains unclear. In the present study, the biological significance of GLI1, GLI2, and GLI3 were analyzed with the aim of developing novel treatments for GBC. It was revealed that GLI2, but not GLI1 or GLI3, was involved in the cell cycle-mediated proliferative capacity in GBC and that GLI2, but not GLI1 or GLI3, was involved in the enhanced invasive capacity through epithelial-mesenchymal transition. Further analyses revealed that GLI2 may function in mediating gemcitabine sensitivity and that GLI2 was involved in the promotion of fibrosis in a mouse xenograft model. Immunohistochemical staining of 66 surgically resected GBC tissues revealed that GLI2-high expression patients had fewer numbers of CD3 + and CD8 + tumor-infiltrating lymphocytes (TILs) and increased programmed cell death ligand 1 (PD-L1) expression in cancer cells. These results suggest that GLI2, but not GLI1 or GLI3, is involved in proliferation, invasion, fibrosis, PD-L1 expression, and TILs in GBC and could be a novel therapeutic target. The results of this study provide a significant contribution to the development of a new treatment for refractory GBC, which has few therapeutic options.

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Computational approaches for characterizing the tumor immune microenvironment

Cited by 32 publications

References 162 publications

Identification of the key genes and characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC)

Identification of the key genes and characterizations of Tumor Immune Microenvironment in Lung Adenocarcinoma (LUAD) and Lung Squamous Cell Carcinoma (LUSC)

Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

GLI2 but not GLI1/GLI3 plays a central role in the induction of malignant phenotype of gallbladder cancer

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