A pan-cancer analysis of the human tumor coagulome and its link to the tumor immune microenvironment

2020 ◽  
Author(s):  
Zuzana Saidak ◽  
Simon Soudet ◽  
Marine Lottin ◽  
Valéry Salle ◽  
Marie-Antoinette Sevestre ◽  
...  
Keyword(s):  
Human Tumor ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

Comparing of pan-cancer tumor immune microenvironment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15100-e15100
Author(s):  
Jiaan Ye ◽  
Longgang Cui ◽  
Xiaochen Zhao ◽  
Guanghui Lan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Cancer Patients ◽  
Killer Cell ◽  
Immune Microenvironment ◽  
Hepatobiliary Cancer ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

e15100 Background: Cancer treatment has entered the era of immune checkpoint inhibitors (ICI), but different tumors have different responses to ICI drugs. For example, non-small cell lung cancer and melanoma have higher response rates to ICIs than colorectal cancer and liver cancer patients. Previous studies have shown that tumor immune microenvironment have a great impact on the efficacy of ICI. Methods: This study retrospectively included pan-cancer patient specimens, using multiple fluorescent labeling immunohistochemistry to explore the differences in the immune microenvironment of different tumors. Shapiro-Wilk was used for normality test, and ANOVA or Kruskal Wallis test was used according to the results. Two-sided P < 0.05 was considered a significant difference. Results: The study included 308 patients, including 119 (38.6%) NSCLC patients, 72 (23.4%) Colorectal cancer patients, 51 (16.6%) Hepatobiliary cancer patients and 66 (21.4%) Others types of cancer patients. Among them, there was 192 (62.3%) Male, and 116 (37.7%) Female, and the median age was 57 (50-66). The proportion of CD8+ T cells and natural killer cell in tumor was statistically different. The proportion of CD8+ T cells in NSCLC, Colorectal cancer, Hepatobiliary cancer and others was 2.16%, 1%, 1.77% and 2.63%, p < 0.01; the proportion of natural killer cell was 16.44 %, 4.91%, 5.58% and 3.29%, p < 0.01. Conclusions: Different tumor types have different immune microenvironments. These results may provide valuable clues for future ICI trail design.

scholarly journals Systematic pan-cancer landscape identifies CARM1 as a potential prognostic and immunological biomarker

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Yingqi Qiu ◽  
Hao Wang ◽  
Peiyun Liao ◽  
Binyan Xu ◽  
Rong Hu ◽  
...  
Keyword(s):  
Tumor Therapy ◽  
Integrated Analysis ◽  
Regulation Of Transcription ◽  
Immune Microenvironment ◽  
Arginine Methyltransferase ◽  
Clinical Prognosis ◽  
Tumor Immune Microenvironment ◽  
Arginine Residues ◽  
Pan Cancer

Abstract Background Belonging to the protein arginine methyltransferase (PRMT) family, the enzyme encoded by coactivator associated arginine methyltransferase 1 (CARM1) catalyzes the methylation of protein arginine residues, especially acts on histones and other chromatin related proteins, which is essential in regulating gene expression. Beyond its well-established involvement in the regulation of transcription, recent studies have revealed a novel role of CARM1 in tumorigenesis and development, but there is still a lack of systematic understanding of CARM1 in human cancers. An integrated analysis of CARM1 in pan-cancer may contribute to further explore its prognostic value and potential immunological function in tumor therapy. Results Based on systematic analysis of data in multiple databases, we firstly verified that CARM1 is highly expressed in most tumors compared with corresponding normal tissues, and is bound up with poor prognosis in some tumors. Subsequently, relevance between CARM1 expression level and tumor immune microenvironment is analyzed from the perspectives of tumor mutation burden, microsatellite instability, mismatch repair genes, methyltransferases genes, immune checkpoint genes and immune cells infiltration, indicating a potential relationship between CARM1 expression and tumor microenvironment. A gene enrichment analysis followed shortly, which implied that the role of CARM1 in tumor pathogenesis may be related to transcriptional imbalance and viral carcinogenesis. Conclusions Our first comprehensive bioinformatics analysis provides a broad molecular perspective on the role of CARM1 in various tumors, highlights its value in clinical prognosis and potential association with tumor immune microenvironment, which may furnish an immune based antitumor strategy to provide a reference for more accurate and personalized immunotherapy in the future.

scholarly journals Pan-Cancer Prognostic, Immunity, Stemness, and Anticancer Drug Sensitivity Characterization of N6-Methyladenosine RNA Modification Regulators in Human Cancers

2021 ◽  
Vol 8 ◽  
Author(s):  
Rui Li ◽  
Yun-Hong Yin ◽  
Xiu-Li Ji ◽  
Xiao Liu ◽  
Jian-Ping Li ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Drug ◽  
Drug Sensitivity ◽  
Rna Modification ◽  
Immune Microenvironment ◽  
Normal Tissues ◽  
Tumor Immune Microenvironment ◽  
Cancer Types ◽  
Pan Cancer

N6-methyladenosine RNA modification plays a significant role in the progression of multiple tumorigenesis. Our study identified the imperative role of m6A regulators in the tumor immune microenvironment, survival, stemness score, and anticancer drug sensitivity of pan-cancer. The Wilcox test was to identify the differential expression between 17 m6A regulators across 33 TCGA cancer types and their normal tissues from UCSC Xena GDC pan-cancer. Survival analysis of m6A-related regulators in 33 TCGA cancer types was identified using the “survival” and “survminer” package. The Spearman correlation test and Pearson correlation test were used to identify the correlation relationship between m6A regulators expression and tumor microenvironment, tumor stem cell score, and drug sensitivity of anticancer drugs. ConsensusPathDB was used for exploring m6A regulators functional enrichment. The 17 (METTL3, WTAP, METTL14, RBM15, RBM15B, VIRMA, HNRNPC, HNRNPA2B1, YTHDC1, ZC3H13, YTHDF1, YTHDC2, YTHDF2, IGF2BP3, IGF2BP1, FTO, and ALKBH5) m6A regulators were differentially expressed in 18 TCGA cancer types and adjacent normal tissues. Correlation analysis indicated that the relationship between the expression of 17 m6A regulators and tumor microenvironment indicated that the higher expression of m6A regulators, the higher the degree of tumor stem cells. The anticancer drug sensitivity analysis indicated that ZC3H13 expression had a positive relationship with anticancer drugs such as selumetinib, dabrafenib, cobimetinib, trametinib, and hypothemycin (p &lt; 0.001). YTHDF2 expression was significantly negatively correlated with the anticancer drug dasatinib (p &lt; 0.001). The pan-cancer immune subtype analysis showed that the 17 m6A regulators were significantly different in immune subtype C1 (wound healing), C3 (inflammatory), C2 (IFN-gamma dominant), C5 (immunological quiet), C4 (lymphocyte depleted), and C6 (TGF-beta dominant) (p &lt; 0.001). Our study provides a comprehensive insight for revealing the significant role of m6A regulators in the tumor immune microenvironment, stemness score, and anticancer drug sensitivity of human cancers.

scholarly journals Multi-Omics Perspective Reveals the Different Patterns of Tumor Immune Microenvironment Based on Programmed Death Ligand 1 (PD-L1) Expression and Predictor of Responses to Immune Checkpoint Blockade across Pan-Cancer

2021 ◽  
Vol 22 (10) ◽  
pp. 5158
Author(s):  
Kaitang Huang ◽  
Meiling Hu ◽  
Jiayun Chen ◽  
Jinfen Wei ◽  
Jingxin Qin ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Great Promise ◽  
Type I ◽  
Z Score ◽  
Immune Microenvironment ◽  
Programmed Death Ligand 1 ◽  
Type Iii ◽  
Programmed Death ◽  
Tumor Immune Microenvironment ◽  
Pan Cancer

Immune checkpoint inhibitor (ICI) therapies have shown great promise in cancer treatment. However, the intra-heterogeneity is a major barrier to reasonably classifying the potential benefited patients. Comprehensive heterogeneity analysis is needed to solve these clinical issues. In this study, the samples from pan-cancer and independent breast cancer datasets were divided into four tumor immune microenvironment (TIME) subtypes based on tumor programmed death ligand 1 (PD-L1) expression level and tumor-infiltrating lymphocyte (TIL) state. As the combination of the TIL Z score and PD-L1 expression showed superior prediction of response to ICI in multiple data sets compared to other methods, we used the TIL Z score and PD-L1 to classify samples. Therefore, samples were divided by combined TIL Z score and PD-L1 to identify four TIME subtypes, including type I (3.24%), type II (43.24%), type III (6.76%), and type IV (46.76%). Type I was associated with favorable prognosis with more T and DC cells, while type III had the poorest condition and composed a higher level of activated mast cells. Furthermore, TIME subtypes exhibited a distinct genetic and transcriptional feature: type III was observed to have the highest mutation rate (77.92%), while co-mutations patterns were characteristic in type I, and the PD-L1 positive subgroup showed higher carbohydrates, lipids, and xenobiotics metabolism compared to others. Overall, we developed a robust method to classify TIME and analyze the divergence of prognosis, immune cell composition, genomics, and transcriptomics patterns among TIME subtypes, which potentially provides insight for classification of TIME and a referrable theoretical basis for the screening benefited groups in the ICI immunotherapy.

Abstract 317: Organoid and TIL co-culture system models the human tumor immune microenvironment and drug sensitivity

2020 ◽  
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
Manabu Futamura ◽  
...  
Keyword(s):  
Culture System ◽  
Drug Sensitivity ◽  
Human Tumor ◽  
Immune Microenvironment ◽  
System Models ◽  
Tumor Immune Microenvironment

scholarly journals High Dimensional Imaging Mass Cytometry Panel to Visualize the Tumor Immune Microenvironment Contexture

2021 ◽  
Vol 12 ◽  
Author(s):  
Roxane Elaldi ◽  
Patrice Hemon ◽  
Luciana Petti ◽  
Estelle Cosson ◽  
Belinda Desrues ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Imaging System ◽  
Human Tumor ◽  
Nerve Fibers ◽  
Tissue Imaging ◽  
High Dimensional ◽  
Staining Procedure ◽  
Mass Cytometry ◽  
Immune Microenvironment ◽  
Tumor Immune Microenvironment

The integrative analysis of tumor immune microenvironment (TiME) components, their interactions and their microanatomical distribution is mandatory to better understand tumor progression. Imaging Mass Cytometry (IMC) is a high dimensional tissue imaging system which allows the comprehensive and multiparametric in situ exploration of tumor microenvironments at a single cell level. We describe here the design of a 39-antibody IMC panel for the staining of formalin-fixed paraffin-embedded human tumor sections. We also provide an optimized staining procedure and details of the experimental workflow. This panel deciphers the nature of immune cells, their functions and their interactions with tumor cells and cancer-associated fibroblasts as well as with other TiME structural components known to be associated with tumor progression like nerve fibers and tumor extracellular matrix proteins. This panel represents a valuable innovative and powerful tool for fundamental and clinical studies that could be used for the identification of prognostic biomarkers and mechanisms of resistance to current immunotherapies.

NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

2020 ◽  
Author(s):  
zhihong sun ◽  
Guanjun Deng ◽  
Xinghua Peng ◽  
Xiuli Xu ◽  
Lanlan Liu ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Photothermal Therapy ◽  
Whole Body ◽  
Mature Dendritic Cell ◽  
Immune Microenvironment ◽  
Highly Efficient ◽  
Tumor Immune Microenvironment ◽  
Shock Proteins ◽  
Mild Temperature ◽  
Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

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