Gene expression profiles of tumor-infiltrating CD8 T cells in hepatocellular carcinoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE132812 | GEO | 2019/08/14
REPOSITORIES: GEO
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Project description:We report the gene expression profiles of FACS-sorted PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma.
2018-11-13 | GSE111389 | GEO
Project description:We report the gene expression profiles of FACS-sorted 4-1BB+PD-1-high, 4-1BB-PD-1-high, and PD-1-int tumor-infiltrating CD8 T cells in hepatocellular carcinoma.
2019-08-14 | GSE132810 | GEO
Project description:Gene expression profiles of tumor-infiltrating CD8 T cells in hepatocellular carcinoma
| PRJNA549153 | ENA
Project description:Adoptive T-cell Therapy (ACT) involves using tumor-infiltrating lymphocytes (TIL) isolated from metastatic melanoma and expanding them ex vivo prior to infusion into lympho-depleted patients. This is one of the most promising approaches to treat metastatic melanoma, with the rates of clinical response between 48-50% based on studies done at NCI, M.D. Anderson Cancer Center (Houston, TX), and Sheba Medical Center (Tel Aviv, Israel). In the Phase II ACT Trial at M.D. Anderson Cancer Center , our group has uncovered an association between positive clinical response and the amount of CD8+ tumor-infiltrating lymphocytes expressing B and T Lymphocyte Attenuator (BTLA), a reported inhibitory receptor on T-cells. We used microarrays to detail the differences in the global programme of gene expression between CD8+BTLA+ vs CD8+BTLA- TILs in order to understand the molecular basis of the clinical association. TILs were isolated by enzymatically digest the melanoma tumor fragments obtained from Stage IIIc/IV melanoma patients at M.D. Anderson Cancer Center. The TILs were expanded with high-dose IL-2 for two weeks prior to sorting by FACS (fluoresecence-activated cell sorter) for CD8+BTLA+ and CD8+BTLA- susbets. RNA was extracted from each sorted subsets and hybridized on Affymetrix microarrays
2013-01-03 | E-GEOD-43260 | biostudies-arrayexpress
Project description:Background: IL-33, a cytokine with pleiotropic functions, is elevated in serum of patients with hepatocellular carcinoma (HCC). This study investigated effects of local IL-33 expression in resected HCC on patient survival and on immunological and molecular tumor microenvironment. Methods: Tissue of resected HCCs was stained for H&E, masson trichrome, alpha smooth muscle actin, IL-33, CD8 and IL-13 and analysed by flow cytometry. Besides histomorphologic evaluation, the immunohistochemical stainings were analysed for the respective cell numbers separately for tumor area, infiltrative margin and distant liver stroma. These findings were correlated with clinical data and patient outcome. Further, gene expression of different HCC risk groups was compared using Micro Arrays. Results: In multivariable analysis, infiltration of HCCs by IL-33+ cells (P=0.032) and CD8+ cells (P=0.014) both independently were associated with prolonged patient survival. Flow cytometry demonstrated that cytotoxically active CD8+CD62L-KLRG1+CD107a+ effectory-memory cells are the main producers of IL-33 in these HCC patients. Using infiltration by IL-33+ and CD8+ cells as two separate factors, a HCC immune score (HCCIS) was designed and evaluated that stratified patient survival (P=0.0004). This HCCIS identified high and low risk patients who differ in gene expression profiles (P<0.001). Conclusion: Infiltration of HCCs by IL-33+ and CD8+ cells is independently associated with prolonged patient survival. We suggest that this is due to an induction of highly effective cytotoxically active CD8+CD62L-KLRG1+CD107a+ effector-memory cells producing IL-33. Based on these two independent factors we established a HCC immune score that provides risk stratification for HCC patients and can be used in the clinical setting. To investigate if HCCIS 0 high risk and HCCIS 2 low risk tumors exhibit a distinct molecular environment and gene expression pattern, RNA from fresh tumor tissue was isolated and analyzed by whole genome Microarray 4 patients with low risk tumors (HCCIS 2) were compared to 4 patients with high risk tumors (HCCIS 0).
2014-12-08 | E-GEOD-63850 | biostudies-arrayexpress
Project description:Gene expression profiles of PD1-high, PD1-intermediate, and PD1-negative tumor-infiltrating CD8 T cells in hepatocellular carcinoma
| PRJNA436904 | ENA
Project description:Study goal is to disclose features of gene expressio profile of non-cancerous liver-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas and tumor-infiltrating lymphocytes of type C hepatitis patients with hepatocellular carcinomas. Keywords: gene expression profile, non-cancerous liver-infiltrating lymphocytes, tumor-infiltrating lymphocytes, type C hepatitis, hepatocellular carcinoma Non-cancerous liver-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected liver tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip. Tumor-infiltrating lymphocytes were obtained by laser capture microdissection from surgically resected cancer tissues of 12 type C hepatitis patients with hepatocellular carcinoma. The mRNA was amplified and expression profile was comprehensively analyzed with reference RNA using oligo-DNA chip.
2010-06-25 | E-GEOD-10461 | biostudies-arrayexpress
Project description:Objective: Cytotoxic T lymphocytes (CTLs) are pivotal in the therapeutic approach to hepatocellular carcinoma (HCC). Recent research has shown that junctional adhesion molecule-like protein (JAML) is capable of promoting the antitumor activity of CD8+ T cells. Our research investigates the role of JAML+ CD8 T cells in HCC. Methods: We employed time-of-flight mass cytometry (CyTOF) and an orthotopic mouse model of HCC to investigate histone modifications in tumor-infiltrating immune cells undergoing immunotherapy. Flow cytometry was used to assess CD4+ T cell differentiation and the expression of JAML in CD8+ T cells infiltrating HCC. Correlation analysis demonstrated a strong positive correlation between LDHA+ CD4 T cells and JAML+ CD8 T cells. Subsequently, we evaluated the therapeutic effects of agonistic anti-JAML antibody, both in conjunction with and without immunotherapy. Finally, RNA sequencing was performed to uncover potential regulatory mechanisms. Results: Immunotherapy substantially elevated the percentage of CD8+ T cells infiltrating HCC and altered histone modifications such as H3K18la in CD4+ T cells. Flow cytometry revealed that lactate promotes the differentiation of CD4+ T cells into Th1 cells. Lactate dehydrogenase A (LDHA) converts pyruvate to lactate. Correlation analysis revealed a strong positive relationship between LDHA+ CD4+ T cells and JAML+ CD8+ T cells in patients responsive to immunotherapy. High expression of JAML in CD8+ T cells is linked to a more favorable prognosis. In vivo experiments, the agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice, independent of the benefit of αPDL1-mediated immunotherapy. Pathway enrichment analysis revealed that JAML enhances CTLs responses through the oxidative phosphorylation pathway. Conclusions: Agonizing JAML can enhance the response of CTLs in treating HCC, and this effect is independent of the benefits provided by αPDL1-mediated immunotherapy, thereby offering a more effective treatment strategy for advanced HCC.
2025-05-14 | GSE279029 | GEO
Project description:The heterogenicity of hepatocellular carcinoma (HCC) remains a key obstacle in turning the majority of ‘immune-cold’ tumors ‘hot’ for effective immune checkpoint inhibitors (ICIs). Through analyzing the naturally-existed ‘hot’ HCC variants, we identified fas-associated death domain (FADD) as a key molecule upregulated in patients with dense tumor-filtrating CD8+T cells and better response to ICIs. Apart from the canonical role in apoptosis pathway, our data showed that CRISPR knockout of hepatoma-intrinsic Fadd led to increased tumor weights in immunocompetent but not immunodeficient mice, accompanied with decreased numbers and IFN-γ/TNF-ɑ production of tumor-filtrating CD8+T cells. Mechanistically, phosphorylated FADD translocated into cell nucleus, where it interacted with Sam68 to upregulate NF-κB transcription of CCL5, thereby promoted CD8+T cell tumor infiltration. Interestingly, anti-PD1 triggered FADD phosphorylation by CD8+T cell-derived IFN-γ/TNF-ɑ in ICI-sensitive, but not resistant tumors. Sequential FADD activation through genetic or pharmacologic approaches to orchestrate p-FADD-CD8+T cell axis therefore overcame ICI resistance in ICI-resistant orthotopic and spontaneous HCC mouse models in vivo. Taken together, our findings may provide insights into the combinatory immunotherapy approaches for the majority of HCC patients in the future.
2025-07-07 | PXD057519 | Pride
Project description:Murine tumour infiltrating lymphocytes (CD8+ T cells) were index-sorted based on expression of CD8a and CD3e. Subsequently cDNA was generated from these samples using the Smart-seq2 protocol. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2016-06-01 | E-ERAD-467 | biostudies-arrayexpress