Browse
Submit Data
Databases
API
Help

Dataset Information

23 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.

ABSTRACT: Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.

SUBMITTER: De Simone M

PROVIDER: S-EPMC5119953 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Reliable evaluation of tumor-infiltrating lymphocytes in pancreatic cancer tissue biopsies.

Project description:Tumor-infiltrating lymphocytes (TILs) represent cancer microenvironment. We previously reported TILs was prognosticators in pancreatic ductal adenocarcinoma (PDAC) patients by immunohistochemically measuring them in surgically-resected tissues. The aim of this study was to assess how best to evaluate TILs in PDAC tissue biopsies. First, we showed expression of CD3, CD4, or CD8 genes in PDAC tissue measured by quantitative RT-PCR (RT-qPCR) was prognostic using 241 surgically-resected specimens. We assessed whether the TILs in biopsied tissues can be effectively evaluated by comparing between immunohistochemistry and RT-qPCR. As a study model, we sampled twenty biopsies from surgically-resected PDAC specimen (n = 17). We investigated the variation levels of TILs in the different biopsies from the same specimen and evaluated using the intraclass correlation coefficient (ICC). The ICC value was 0.58 for CD3, 0.61 for CD4, and 0.46 for CD8, respectively; these ICC values meant correlations of "moderate" to "substantial" levels. To reach "near perfect", 3, 3, and 5 times biopsies were necessary for CD3, CD4, and CD8, respectively. When ICC values of immunolabeled TILs were of "low", ≥6 times biopsies were necessary to reach "moderate" levels. We found that TILs measured by RT-qPCR and repeated sampling increased reliability in TILs detected from biopsied PDAC tissues.

| S-EPMC6383689 | biostudies-literature

Tumor-infiltrating lymphocytes in melanoma.

Project description:Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the most effective treatment for patients with metastatic melanoma. With higher response rates than ipilimumab or IL-2, and longer durations of response than vemurafenib, TIL therapy carries the potential to transform current outcomes in melanoma, while also defining the way cell-based immunotherapy gets incorporated into mainstream cancer treatment. This paper will review the current state of TIL therapy in melanoma, the strategies to improve its efficacy, the current obstacles, and future directions to expand the availability of TIL to the general patient population.

| S-EPMC3462483 | biostudies-literature

The three-dimensional landscape of the genome in human brain tissue unveils regulatory mechanisms leading to schizophrenia risk.

Project description:Recent advances in our understanding of the genetic architecture of schizophrenia have shed light on the schizophrenia etiology. While common variation is one of the major genetic contributors, the majority of common variation reside in non-coding genome, posing a significant challenge in understanding the functional impact of this class of genetic variation. Functional genomic datasets that range from expression quantitative trait loci (eQTL) to chromatin interactions are critical to identify the potential target genes and functional consequences of non-coding variation. In this review, we discuss how three-dimensional chromatin landscape, identified by a technique called Hi-C, has facilitated the identification of potential target genes impacting schizophrenia risk. We outline key steps for Hi-C driven gene mapping, and compare Hi-C defined schizophrenia risk genes defined across developmental epochs and cell types, which offer rich insights into the temporal window and cellular etiology of schizophrenia. In contrast with a neurodevelopmental hypothesis in schizophrenia, Hi-C defined schizophrenia risk genes are postnatally enriched, suggesting that postnatal development is also important for schizophrenia pathogenesis. Moreover, Hi-C defined schizophrenia risk genes are highly expressed in excitatory neurons, highlighting excitatory neurons as a central cell type for schizophrenia. Further characterization of Hi-C defined schizophrenia risk genes demonstrated enrichment for genes that harbor loss-of-function variation in neurodevelopmental disorders, suggesting a shared genetic etiology between schizophrenia and neurodevelopmental disorders. Collectively, moving the search space from risk variants to the target genes lays a foundation to understand the neurobiological basis of schizophrenia.

| S-EPMC6748876 | biostudies-literature

Characterization of infiltrating lymphocytes in human benign and malignant prostate tissue.

Project description:Immune checkpoint blockade has shown promising results in numerous cancer types. However, in prostate cancer (PC), absent or limited responses have been reported. To investigate further, we compared the phenotype of infiltrating T-cells isolated from prostate tissue from patients with PC (n = 5), benign prostatic hyperplasia (BPH) (n = 27), BPH with concurrent PC (n = 4) and controls (n = 7). The majority of T-cells were CD8+ and had a CCR7-CD45RO+ effector memory phenotype. However, the yield of T-cells isolated from PC lesions was on average 20-fold higher than that obtained from control prostates. Furthermore, there were differences between the prostate conditions regarding the percentage of T-cells expressing several activation markers and co-inhibitory receptors. In conclusion, many prostate-infiltrating T-cells express co-inhibitory receptors PD-1 and LAG-3, regardless of prostate condition. Despite the observed increase in counts and percentages of PD-1+ T-cells in PC, the concomitant demonstration of high percentage of PD-1+ T-cells in control prostates suggests that PD-1 may play a role in controlling the homeostasis of the prostate rather than in contributing to PC-associated immune-suppression. Thus, PD-1 may not be a good candidate for checkpoint blockade in PC and these data are relevant for evaluation of clinical trials and in designing future immunotherapeutic approaches of PC.

| S-EPMC5601136 | biostudies-literature

Non-cancerous liver infiltrating lymphocytes of hepatitis C and tumor-infiltrating lymphocytes

Project description: Not available

| S-DIXA-D-1003 | biostudies-other

Tumor infiltrating lymphocytes in ovarian cancer.

Project description:The accumulation of tumor infiltrating lymphocytes (TILs) in ovarian cancer is prognostic for increased survival while increases in immunosuppressive regulatory T-cells (Tregs) are associated with poor outcomes. Approaches that bolster tumor-reactive TILs may limit tumor progression. However, identifying tumor-reactive TILs in ovarian cancer has been challenging, though adoptive TIL therapy in patients has been encouraging. Other forms of TIL immunomodulation remain under investigation including Treg depletion, antibody-based checkpoint modification, activation and amplification using dendritic cells, antigen presenting cells or IL-2 cytokine culture, adjuvant cytokine injections, and gene-engineered T-cells. Many approaches to TIL manipulation inhibit ovarian cancer progression in preclinical or clinical studies as monotherapy. Here, we review the impact of TILs in ovarian cancer and attempts to mobilize TILs to halt tumor progression. We conclude that effective TIL therapy for ovarian cancer is at the brink of translation and optimal TIL activity may require combined methodologies to deliver clinically-relevant treatment.

| S-EPMC4622931 | biostudies-literature

Distinctive features of tumor-infiltrating ?? T lymphocytes in human colorectal cancer.

Project description:?? T cells usually infiltrate many different types of cancer, but it is unclear whether they inhibit or promote tumor progression. Moreover, properties of tumor-infiltrating ?? T cells and those in the corresponding normal tissue remain largely unknown. Here we have studied features of ?? T cells in colorectal cancer, normal colon tissue and peripheral blood, and correlated their levels with clinicopathologic hallmarks. Flow cytometry and transcriptome analyses showed that the tumor comprised a highly variable rate of TILs (5-90%) and 4% ?? T cells on average, with the majority expressing V?1. Most V?1 and V?2 T cells showed a predominant effector memory phenotype and had reduced production of IFN- ? which was likely due to yet unidentified inhibitory molecules present in cancer stem cell secretome. Transcriptome analyses revealed that patients containing abundant ?? T cells had significantly longer 5-year disease free survival rate, suggesting their efficacy in controlling tumor at very early stage.

| S-EPMC5665062 | biostudies-literature

Landscape of tumor-infiltrating T cell repertoire of human cancers.

Project description:We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p.Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes.

| S-EPMC5298896 | biostudies-literature

Identification of the Tumor Infiltrating Lymphocytes (TILs) Landscape in Pure Squamous Cell Carcinoma of the Bladder.

Project description:Background: Tumor infiltrating lymphocytes (TILs) are known as important prognostic biomarkers and build the fundament for immunotherapy. However, the presence of TILs and its impact on outcome in pure squamous cell carcinoma (SCC) of the bladder remains uncertain. Methods: Out of 1600 patients undergoing radical cystectomy, 61 patients revealed pure bladder SCC in the final histopathological specimen. Retrospectively, immunohistochemical staining was performed on a subset of TILs (CD3+, CD4+, CD8+, CD20+). Endpoints were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). The Kaplan-Meier method was used to evaluate survival outcomes. Results: Strong infiltration of CD3+ was found in 27 (44%); of CD4+ in 28 (46%); of CD8+ in 26 (43%); and of CD20+ in 27 tumors (44%). Improved OS was observed for strong CD3+ (p < 0.001); CD4+ (p = 0.045); CD8+ (p = 0.001); and CD20+ infiltration (p < 0.001). Increased rates of PFS were observed for CD3+ (p = 0.025) and CD20+ TILs (p = 0.002). In multivariate analyses, strong CD3+ (HR: 0.163, CI: 0.044-0.614) and strong CD8+ TILs (HR: 0.265, CI: 0.081-0.864) were revealed as predictors for OS and the strong infiltration of CD20+ cells (HR: 0.095, CI: 0.019-0.464) for PFS. Conclusions: These first results of TILs in bladder SCC revealed predictive values of CD3+, CD8+ and CD20+.

| S-EPMC9406640 | biostudies-literature

Prevalence of tumor-infiltrating lymphocytes and PD-L1 expression in the soft tissue sarcoma microenvironment.

Project description:The prognostic and predictive implications of programmed death-ligand 1 (PD-L1) is unknown in sarcoma. We sought to examine the immune milieu in sarcoma specimens. We evaluated PD-L1 expression by immunohistochemistry in sarcoma specimens and quantified tumor-infiltrating lymphocytes (TIL). We correlated expression with clinical parameters and outcomes. Fifty sarcoma patients treated at Memorial Sloan Kettering Cancer Center were selected. Using the DAKO PD-L1 immunohistochemistry assay and archival formalin-fixed paraffin-embedded tissue specimens; PD-L1 expression was examined. Macrophage and lymphocyte PD-L1 status was determined qualitatively. TIL was quantified. Associations between PD-L1 expression in tumor, macrophages and lymphocytes, TIL and clinical-pathological characteristics were performed. The median age was 46 years (range, 22-76), and 66% of patients were men. Tumor, lymphocyte and macrophage PD-L1 expression was noted in 12%, 30% and 58%, respectively, with the highest prevalence in gastrointestinal stromal tumors (29%). Lymphocyte and macrophage infiltration was present in 98% and 90%, respectively. There was no association between clinical features, overall survival and PD-L1 expression in tumor or immune infiltrates. Lymphocyte and macrophage infiltration is common in sarcoma, but PD-L1 tumor expression is uncommon in sarcoma with the highest frequency observed in gastrointestinal stromal tumors. There was no association between PD-L1 expression, TIL and clinicopathological features and overall survival; however, this is limited by the heterogenous patient sample and minimal death events in the studied cohort.

| S-EPMC5505649 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data