Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer

ABSTRACT: Tumors weakly infiltrated by T lymphocytes poorly respond to immunotherapy. We aimed to unveil malignancy-associated programs regulating T cell entrance, arrest, and activation in the tumor environment. Differential expression of cell adhesion and tissue architecture programs, particularly the presence of the membrane tetraspanin claudin (CLDN)18 as a signature gene, demarcated immune-infiltrated from immune-depleted mouse pancreatic tumors. In human pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer, CLDN18 expression positively correlated with more differentiated histology and favorable prognosis. CLDN18 on the cell surface promoted accrual of cytotoxic T lymphocytes (CTLs), facilitating direct CTL contacts with tumor cells by driving the mobilization of the adhesion protein ALCAM to the lipid rafts of the tumor cell membrane through actin. This process favored the formation of robust immunological synapses (ISs) between CTLs and CLDN18-positive cancer cells, resulting in increased T cell activation. Our data reveal an immune role for CLDN18 in orchestrating T cell infiltration and shaping the tumor immune contexture.

ORGANISM(S): Mus musculus

PROVIDER: GSE230868 | GEO | 2024/05/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Mahasa2016-tumor–immune surveillance

Project description:We present a novel mathematical model involving various immune cell populations and tumor cellpopulations. The model describes how tumor cells evolve and survive the brief encounter with theimmune system mediated by natural killer (NK) cells and the activated CD8þcytotoxic T lymphocytes(CTLs). The model is composed of ordinary differential equations describing the interactions betweenthese important immune lymphocytes and various tumor cell populations. Based on up-to-dateknowledge of immune evasion and rational considerations, the model is designed to illustrate how tu-mors evade both arms of host immunity (i.e.innate and adaptive immunity). The model predicts that(a) an influx of an external source of NK cells might play a crucial role in enhancing NK-cell immunesurveillance; (b) the host immune system alone is not fully effective against progression of tumor cells;(c) the development of immunoresistance by tumor cells is inevitable in tumor immune surveillance. Ourmodel also supports the importance of infiltrating NK cells in tumor immune surveillance, which can beenhanced by NK cell-based immunotherapeutic approaches.

2020-03-20 | MODEL2003040001 | BioModels

Tumor-associated macrophages expressing the transcription factor IRF8 promote T cell exhaustion in cancer

Project description:Tumor progression is associated with overstimulation of cytotoxic T lymphocytes (CTLs), resulting in a dysfunctional state of exhaustion. However, the identity of antigen-presenting cells that drive CTL exhaustion is poorly defined. Here we show that tumor-associated macrophages (TAMs) expressing the transcription factor interferon regulatory factor-8 (IRF8) promote CTL exhaustion in a murine model of breast cancer. While CTL priming in tumor-draining lymph nodes was enabled by IRF8-dependent type 1 dendritic cells, CTL exhaustion in tumor required TAM expression of IRF8 that supported the cancer cell antigen-presenting function of TAMs. Macrophage-specific ablation of IRF8 reversed exhaustion of cancer cell antigen-reactive CTLs, and suppressed tumor growth. Analysis of the immune-infiltrated human renal cell carcinoma tumors revealed abundant TAMs that expressed IRF8 and were enriched for an IRF8 gene expression signature. Furthermore, the TAM-IRF8 signature co-segregated with CTL exhaustion signatures across multiple cancer types. Thus, CTL exhaustion is promoted by TAMs via IRF8.

2022-09-06 | GSE212643 | GEO

Gene-expression profiles of ascites-cytology-positive ovarian cancer

Project description:Ovarian cancer often progresses by disseminating to the peritoneal cavity, but how the tumor cells evade host immunity during this process is poorly understood. Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Positive cytology in ascites was a significant poor prognostic factor in ovarian cancer. Microarray profiles of cytology-positive cases showed significant correlations with Gene Ontology terms related to immune system process. Microarray and immunohistochemistry in human ovarian cancer revealed significant correlation between PD-L1 expression and positive cytology. PD-L1 expression on mouse ovarian cancer cells was induced upon encountering lymphocytes in the course of peritoneal spread in vivo and upon co-culturing with lymphocytes in vitro. Tumor cell lysis by CTLs was attenuated when PD-L1 was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in human ovarian cancer tissue from ascites-cytology-positive or -negative patients.

2012-07-09 | E-GEOD-39204 | biostudies-arrayexpress

The mRNA and lncRNA profiles of the T cells activated by breast tumor-specific DCs pulsed by MDA-MB-231 lysates at day 0, day 1 and day 6

Project description:Activation induced cell death (AICD) of T lymphocytes may be exploited by cancers to eliminate cytotoxic T cells (CTLs). Here, we demonstrated excessive apoptosis of tumor antigen-specific CTLs in breast and lung cancers. Interestingly, NKILA, an NF-κB interacting lncRNA, sensitizes CTLs to AICD by inhibiting NF-κB activities after their activation. In vivo, administering CTLs with NKILA silencing into immunocompromised mice with breast cancer patient derived xenografts (PDXs) effectively inhibits PDX growth by increasing CTL infiltration. Clinically, NKILA was overexpressed in the tumor specific CTLs of breast and lung cancers, which was associated with less CTL infiltration in the tumors and shorter patient survival. Our findings present the first evidence that AICD in patient tumor-specific CTLs is crucial to cancer immune evasion, and targeting NKILA in CTLs emerges as a novel anti-tumor immunotherapy.

2018-07-23 | GSE108819 | GEO

IFN-γ Upregulates Survivin and Ifi202 Expression to Induce Survival and Proliferation of Tumor-Specific T Cells

Project description:Transcriptional profiling of mouse tumor-specific cytotoxic T lymphocytes (CTL) comparing activation-induced gene expression profiles induced by tumor-specific antigen (Ag) and CD3 mAb. CTLs were stimulated with either Ag or CD3 mAb for 3 and 24 h, respectively. The stimulated CTLs were compared to un-stimulated CTLs. The objective was to identify differential gene expression profiles induced by the two activation (Ag vs CD3 mAb) conditions. Two-condition experiments, un-stimulated vs stimulated CTLs. Biological replicates: 3 replicates for each comparison. Unstimulated CTLs were compared to stimulated CTLs (Ag and CD3 mAb, respectively).

2010-12-03 | E-GEOD-22890 | biostudies-arrayexpress

Gene-expression profiles of PD-L1-affected CD8+ T cells

Project description:Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Tumor cell lysis by CTLs was attenuated when PD-L1 on tumor cells was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. Gene expression profile of mouse CTLs caused by PD-L1-overexpressing ovarian cancer was related to human CTLs exhaustion. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in OT-1 mouse CD8+ T cells that were co-incubated with OVA peptide-loaded ID8 mouse ovarian cancer cell lines. CTLs from 4 mice were devided into 2 groups, and co-incubated with PD-L1-overexpressed ID8 or PD-L1-depleted ID8.

2012-07-09 | E-GEOD-39205 | biostudies-arrayexpress

Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer [HNSCC]

Project description:Therapies that boost the anti-tumor responses of cytotoxic lymphocytes (CTLs) have shown promise in the clinic. However, clinical responses to currently available immunotherapeutic agents vary considerably, for which the molecular basis is unclear. To date, unbiased transcriptomic studies of CTLs in human cancers have been performed in whole tumors or cells obtained from peripheral blood or metastatic sites of heavily pre-treated patients. We performed global transcriptional profiling of CTLs in tumors and adjacent non-tumor tissue from treatment-naïve patients with early stage lung cancer to define the molecular features associated with robustness of anti-tumor immune responses. We observed major differences in the transcriptional program of tumor-infiltrating CTLs that are shared across tumor subtypes. Pathway analysis revealed enrichment of genes in cell cycle, T cell receptor (TCR) activation and co-stimulation pathways, indicating tumor-driven expansion of presumed tumor antigen-specific CTLs. We also observed marked heterogeneity in the expression of molecules associated with TCR activation and immune checkpoints such as 4-1BB, PD1, TIM3, and their expression was positively correlated with the density of tumor-infiltrating CTLs. Interestingly, transcripts linked to tissue-resident memory cells (TRM), such as CD103, were enriched in tumors containing a high density of CTLs, and CTLs from CD103high tumors displayed features of enhanced cytotoxicity, implying better anti-tumor activity. In an independent cohort of 689 lung cancer patients, we confirmed that patients with CD103high (TRM rich) tumors survived significantly longer. In summary, we define the molecular fingerprint of tumor-infiltrating CTLs at the site of primary tumor and identify a number of novel targets that may be important in modulating the magnitude and specificity of anti-tumor immune responses in lung cancer.

2017-06-19 | GSE90729 | GEO

Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer [NSCLC]

2017-06-19 | GSE90728 | GEO

Gene-expression profiles of ascites-cytology-positive ovarian cancer

2012-07-10 | GSE39204 | GEO

Roles of membrane-Anchoring ARHGAP fusions in peritoneal metastasis of gastric and pancreatic cancer.

Project description:Diffuse-type gastric cancer (DGC) frequently metastasizes to the peritoneal cavity and causes malignant ascites. Although recent studies revealed that RHOA mutation and CLDN18-ARHGAP6/26 fusions are a hallmark of DGC, their roles are largely unknown. Here, we report the roles of two novel ARHGAP fusions (RP2-ARHGAP6 and OCLN-ARHGAP26) and the above CLDN18-ARHGAP26 fusion in ascites-derived DGC cell lines. A series of experiments revealed that X-ARHGAP6 /26 fusion acts as an inhibitor of RhoA and further suggested that the ARHGAP6 fusion induces cell-adhesion loss and maintains a putative ALDH-high cancer stem cell population, whereas the ARHGAP26 fusion evades apoptosis. Notably, these ARHGAP6/26 fusions were frequently found not only in the ascites of DGC but also in that of pancreatic cancer (12% and 38%, respectively). Together, these data demonstrate that ARHGAP6/26 fusions are useful for developing therapeutics and diagnostics for peritoneal metastasis control of DGC and pancreatic cancer. We used microarrays to identify gene sets regulated by RP2-ARHGAP6-centered signaling in DGC cells.

2020-12-31 | GSE100627 | GEO

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