CD8 TIL subsets isolation from early-stage, untreated NSCLC
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE232899 | GEO | 2023/10/09
REPOSITORIES: GEO
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Project description:CD8 TIL subsets isolation from early-stage, untreated NSCLC
| PRJNA974395 | ENA
Project description:For the iMPQAT analysis, we retrospectively collected frozen samples of the tumors from 36 patients with lung adenocarcinoma (n = 12), squamous cell carcinoma (n = 12) and LD-SCLC[TG1] (n = 12) who had undergone surgical resection at Kyushu University Hospital between January 2012 and July 2018. Among 12 patients with SCLC, frozen samples of the normal lung tissue were available in 6 patients.
2023-07-01 | PXD035054 | JPOST Repository
Project description:CD8+ tumor-infiltrating lymphocytes (TILs) comprise phenotypically and functionally heterogeneous subpopulations. Of these, effector memory CD45RA-expressing CD8+ T cells (Temra) have been discovered and characterized as the most terminally differentiated subset. However, their exact ontogeny and physiological importance in association with tumor progression remain poorly understood. We analyzed primary tumors and peripheral blood samples from 26 patients with non-small cell lung cancer and analyzed their phenotypes and functional characteristics using flow cytometry, RNA-sequencing, and bioinformatics. We found that tumor-infiltrating Temra (tilTemra) cells largely differ from peripheral blood Temra (pTemra), with distinct transcriptomes and functional properties. Notably, although majority of the pTemra was CD27-CD28- double-negative (DN), a large fraction of tilTemra population was CD27+CD28+ double-positive (DP), a characteristic of early-stage, less differentiated effector cells. Trajectory analysis revealed that CD8+ TILs undergo a divergent sequence of events for differentiation into either DP or DN tilTemra. Such a differentiation toward DP tilTemra relied on persistent expression of CD27 and CD28 and was associated with weak T cell receptor engagement. Thus, a higher proportion of DP Temra was correlated with lower immunogenicity of tumor antigens and consequently lower accumulation of CD8+ TILs. These data suggest a complex interplay between CD8+ T cells and tumors and define DP Temra as a unique subset of tumor-specific CD8+ TILs that are produced in patients with relatively low immunogenic cancer types, predicting immunogenicity of tumor antigens and CD8+ TIL counts, a reliable biomarker for successful cancer immunotherapy.
2021-09-14 | GSE184053 | GEO
Project description:SAGE analysis of alveolar macrophages from metastatic lung and untreated lung
| PRJNA418727 | ENA
Project description:Programmed death-ligand 1 (PD-L1) is suggested to be a predictive biomarker in non-small-cell lung carcinoma (NSCLC). However, the differential expression of PD-L1 in primary lung tumor vs. synchronous metastases, especially brain metastasis (BM), remains unclear. This study assessed the concordance of PD-L1 expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and CD8+ TIL intensity between primary lung tumors and synchronous BMs from 24 NSCLC patients. PD-L1, CD3, and CD8 positivity was determined by immunohistochemistry (IHC). PD-L1 scoring was based on the proportion of tumor cells with membranous expression of PD-L1 and the cutoff values <1%, 1-49%, and ?50%. CD3 and CD8 positivity in TILs was evaluated semi-quantitatively and the proportion of CD3+/CD8+ TILs was determined. PD-L1 expression on tumor cells and TILs was evaluated in relation to CD3+/CD8+ TIL proportions and the intensity of CD8+ TILs between the paired primary lung and BM tissues. In the primary lung tumors, PD-L1 positivity was observed in 25%, 37.5%, and 37.5% cases for the cutoff values <1%, 1-49%, and ?50%, respectively. PD-L1 expression on tumor cells was strongly correlated between the paired primary lung and BM tissues, in all cutoff groups. However, PD-L1 expression on TILs and the proportion of CD3+/CD8+ TILs were not strongly correlated in all three groups between the paired primary lung tumors and BMs. The intensity of CD8+ TILs was concordant in only 54.16% of the paired primary lung tumors and BMs. This study showed a high concordance of PD-L1 expression in neoplastic cells between primary NSCLC and synchronous BMs.
| S-EPMC7416171 | biostudies-literature
Project description:Purpose: To determine whether distinct tissue immune microenvironments differentially impact on clinical outcome in non-small cell lung cancer (NSCLC), an extended analysis of PD-1/PD-L1 and Tumor Infiltrating Lymphocytes (TILs) was performed. Materials and Methods: 1016 NSCLC mRNA-sequence samples from The Genome Data Analysis Center (TCGA) and 275 NSCLC mRNA-microarray samples from Gene Expression Omnibus (GEO) were included as testing cohort and validation cohort respectively. Enrichment scores of CD8+ T cells' metagene were used for quantifying its infiltrating density. Based on the median values of CD8+ T cell density and PD-1/PD-L1 mRNA expression, the samples were classified into four Tumor Immune Microenvironment types (TIMTs). Overall survival, as well as clinicopathological features, mutational profiles, mismatch repair score etc. were compared across the four types. Results: Neither PD-1 expression nor PD-L1 expression was associated with outcome in the overall NSCLC. Classification of TIMT based on PD-1/PD-L1 and CD8+ TIL could efficiently classify patients of different survival in ADC but not SCC, with the best overall survival achieved in TIMT3 (high CD8+ TIL and low PD-1/PD-L1), whereas TIMT2 (low CD8+ TIL and high PD-1/PD-L1) manifested the worst outcome. TIMT classification based on PD-1/ CD8+ TIL could better stratify patient of different prognosis than PD-L1/ CD8+ TIL based classification. EGFR wide type and IFN? overexpression were associated with TIMT4 (high PD-1/PD-L1 and high CD8+ TIL), whereas tumor mutational burden (TMB) manifested no significant difference across four TIMTs. Conclusion: The classification of tumors into four microenvironment subtypes based on PD-1/PD-L1 status and CD8+ TIL is an appropriate approach to stratify patients of different clinical outcome and better guide the practical use of immunotherapy.
| S-EPMC6329863 | biostudies-other
Project description:Lipidomics, proteomics and metabolomics characterization of the ontogeny of lipid, protein and metabolite changes during normal postnatal lung development
2018-10-22 | PXD004651 | Pride
Project description:CD3 T cells were first primed for 7 days with allogeneic APC in the presence of absence of ILT3-Fc, then were restimulated for 4 hours (with the original priming APC) CD8 T cells were magnetically sorted from these cultures, and lysed for gene chip profiling. Two condition experiments, ILT3Fc treated vs untreated CD8+ T cells, (4) ILT3Fc treated replicates and (4) untreated replicates
2010-09-02 | E-GEOD-23922 | biostudies-arrayexpress
Project description:GaST-seq spatial transcriptomics untreated leaf
| PRJEB31314 | ENA
Project description:To identify genes associated with lung cancer progression, we examined gene expression profiles of tumor cells from 20 patients with primary, untreated non-small cell lung cancer (10 adenocarcinomas (AC) and 10 squamous cell carcinomas (SCC)) in comparison to lung tissue of 23 patients with stage IIIB or stage IV non-small cell lung cancer (15 AC and 8 SCC). Bronchoscopical biopsies from patient with recurrent lung tumor were taken after initial treatment. Cancer cells were isolated using laser capture microdissection in order to obtain pure samples of tumor cells. For expression analysis, microarrays covering 8793 defined genes (Human HG Focus Array, Affymetrix) were used. Array data were normalized and analysed for significant differences using variance stabilizing transformation (VSN) and significance analysis of microarrays (SAM), respectively. Genes were considered to be up- or down-regulated when the ratio between primary and recurrent tumor samples were at least 1.5-fold differentially expressed with an estimated false discovery rate: < 5%. Based on differentially expressed genes, primary cancer samples could be separated from recurrent tumor samples. We identified 115 and 124 significantly regulates genes in AC and SCC, respectively. For example, in recurrent AC we found increased expression of genes related to the wingless (FZD6, RYK, MYC) and calcium (CALM1, ATB2B1, S100A2) signalling pathways which might play a role in metastasis of tumor cells. Other differentially expressed genes were related to cell cycle (CCND1, CDK2), transcription factors (TTF1, TAF2, YY1), nuclear mRNA splicing and mRNA processing (SFRS1, HNRPL), protein-nucleus import (NUTF2, KPNB1, NUP50) and chromatin modification (HIST1H4C, SMARCC1). In SCC, we found an increased expression of CTNNB1, an important mediator in wingless signalling pathway. Among the down-regulated genes in SCC, the utmost fraction belonged to genes coding for ubiquitin mediated proteolysis (UCHL1, PSMA3, COPS6) and ribosomal proteins (RPS26, RPL7A, RPS15). Other down regulated genes were related to transcription factors (TCEA2, TAF10), nuclear mRNA splicing and mRNA processing (SNRPD2, HNRPM). In conclusion, a distinct pattern of gene expression is found during the progression from primary carcinoma to recurrent NSCLC. Our microarray-based expression profiling revealed interesting novel candidate genes and pathways that may contribute to lung cancer progression. Experiment Overall Design: - 20 patients with primary, untreated non-small cell lung cancer (10adenocarcinomas (AC) and 10 squamous cell carcinomas (SCC)) in comparison to lung tissue of 23 patients with stage IIIB or stage IV non-small cell lung cancer (15 AC and 8 SCC) Experiment Overall Design: - Human HG Focus Array, Affymetrix) were used Experiment Overall Design: - Array data were normalized and analysed for significant differences using variance stabilizing transformation (VSN) and significance analysis of microarrays (SAM) Experiment Overall Design: - Genes were considered to be up- or down-regulated when the ratio between primary and recurrent tumor samples were at least 1.5-fold differentially expressed with an estimated false discovery rate: < 5%
2008-06-15 | E-GEOD-7880 | biostudies-arrayexpress