Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive Landscape of Resistance Mechanisms for Neoadjuvant Therapy in Esophageal Squamous Cell Carcinoma by single-cell Transcriptomics

ABSTRACT: Neoadjuvant therapy has been shown to improve survival for locally advanced esophageal squamous cell carcinoma (ESCC). However, some cases may acquire therapy resistance and the mechanism is still unclear. Here, we applied single-cell RNA sequencing on 7 ESCC patients with neoadjuvant therapy and 2 ESCC patients underwent general surgery alone to delineate the tumor heterogeneity, tumor microenvironment (TME) and potential hallmarks of therapy resistance. In total, 13 tumor cell lineages and its corresponding lineage-specific gene signatures, pathway activities, and transcription factors were identified, representing different mechanisms and hallmarks of neoadjuvant therapy resistance, such as oxidative stress response, hypoxia, DNA repair, ECM and EMT. Typically, tumor cell lineage Ep-C2 with signatures of oxidative stress response showed the strongest resistance to neoadjuvant therapy, particularly under chemoradiotherapy and immunotherapy combination. Excepting for the resistance mechanisms associated with tumor cell lineages, we also investigated three TME characteristics response to neoadjuvant therapy resistance, including the infiltration of cytotoxic-insufficient GZMK+ effector memory T cells, angiogenesis-promoting effect of myeloid lineages and the cell-cell communication of tumor-associated fibroblasts. These hallmarks of neoadjuvant therapy will help us to understand the therapy resistance in ESCC and provide important clues to identify potential targets to improve therapy sensitivity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221561 | GEO | 2023/08/14

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Single cell RNA-sequence reveals the effect of neoadjuvant chemotherapy on immune cells in human esophageal squamous cell carcinoma.

Project description:In this study, we comprehensively investigated the impact of neoadjuvant chemotherapy (NAC) on immune cells in the tumor microenvironment (TME) of esophageal squamous cell carcinoma (ESCC) using single cell RNA sequence. CD8+ T cells, CD4+ T cells, dendritic cells, and macrophages in TME of ESCC all showed higher levels of anti-tumor immune response in the NAC(+) group than in the NAC(-) group. Furthermore, the immune cells in the TME of the NAC(+) group interacted with each other to enhance the anti-tumor immune response. Our results suggest that NAC potentially enhance the anti-tumor immune response of immune cells in the TME.

2023-03-31 | GSE197677 | GEO

Intra-tumoural Microbiota Remodels the Tumour Immune

Project description:Esophageal squamous cell carcinoma (ESCC) accounts for ~90% of all cases of esophageal cancer and the sixth most common cause of cancer related death worldwide. 1, 2 It remains a globally challenging disease and mostly diagnosed cases requires a multidisciplinary approach with extensive treatments including surgery, chemoradiotherapy and/or chemotherapy. ESCC has a relatively high tumor mutational burden,3 suggesting that it could benefit from PD-1 blockade. Recently, three phase III clinical trials reported that PD-1 blockade significantly improved progression-free survival (PFS) and overall survival (OS) when combined with chemotherapy as first-line therapy in advanced/metastatic ESCC.4, 5 Moreover, in 2021 ASCO annual meeting, two phase II clinical trials reported that neoadjuvant chemo-immunotherapy (NACI) induced an obvious improvement of the pathologic complete response (pCR) for resectable ESCC (35. 3% and 42.5%, respectively). Several phase III trials on this topic are ongoing (NCT04807673, NCT04848753, NCT04280822) (https://clinicaltrial s.gov/ct2/show/NCT04807673), indicating that neoadjuvant NACI would become promising treatment for locally advanced ESCC. Nevertheless, not all ESCC patients could respond to NACI. Patients who responded well or poorly to neoadjuvant immunotherapy were treated with surgery. We collected samples from these patients and conducted single-cell sequencing to analyze the tumor immune microenvironment of patients with different therapeutic effects, compare the differences in immune cell composition in the immune microenvironment, and explore more effective neoadjuvant therapy methods.

2023-07-07 | GSE203115 | GEO

Immune impact of neoadjuvant chemo/radio-therapy in the pancreatic cancer microenvironment

Project description:Pancreatic ductal adenocarcinoma (PDAC) has dismal five-year survival (<9%). We examined the impact of neoadjuvant FOLFIRINOX alone or in combination with radiation therapy (conventional radiotherapy, XRT, or stereotactic body radiotherapy, SBRT) on immunologically relevant genes in the PDAC tumor microenvironment (TME). We hypothesize conventional therapies may induce immune alterations in the TME that can be leveraged to enhance the efficacy of immunotherapy in PDAC. PDAC patients who underwent upfront surgical resection or who received neoadjuvant FOLFIRINOX with or without neoadjuvant radiotherapy followed by surgical resection were selected for study. The expression of 730 immunologically relevant transcripts was quantitated using the Nanostring PanCancer immune profiling panel (Platform GPL19965). This analysis identified189 genes that were differentially expressed at the RNA level on the basis of neoadjuvant therapy. On average specimens were obtained 6.6-17.0 weeks after the conclusion of neoadjuvant therapy, depending on treatment group. These data provide insight into the immunological effects of standard of care neoadjuvant therapy for resectable/borderline-resectable PDAC. This work provides data to guide strategic new combination therapies for pancreatic cancer.

2019-04-09 | GSE129492 | GEO

Dissecting esophageal squamous-cell carcinoma ecosystem by single-cell transcriptomic analysis

Project description:Esophageal squamous-cell carcinoma (ESCC), one of the most prevalent and lethal malignant disease, has a complex but unknown tumor ecosystem. Here, we decipher for the first time the full compositions of ESCC tumor based on analyzing 208,659 single-cell transcriptomes in ESCC derived from 60 individuals. We identify 8 essential expression programs from malignant epithelial cells and discovered 43 cell types including 26 immune cell and 17 nonimmune stromal cell subtypes in the tumor microenvironment (TME), and also explicate the interactions between cancer cells and other cells and the interactions among different cell types in the TME. Moreover, we have linked the cancer cell transcriptomes to the somatic mutations and identified several markers significantly associated with survival time in patients, which may be relevant to precision cares of ESCC patients. These results renew our understanding of ESCC and provide a valuable example and resource for investigating other types of solid tumor.

2020-10-29 | GSE160269 | GEO

Response and recurrence correlates in patients treated with neoadjuvant anti-PD-1 therapy for resectable oral-cavity squamous cell carcinoma

Project description:Neoadjuvant PD-1 blockade may be efficacious in patients with high-risk, resectable oral-cavity, head-and-neck cancer. To explore correlates of response patterns to neoadjuvant nivolumab treatment and post-surgical recurrences, we analyzed longitudinal tumor and blood samples in a cohort of 12 patients displaying 33% responsiveness. Pretreatment tumor-based detection of FLT4 mutations and PTEN signature enrichment favors response, and high tumor mutational burden improves recurrence-free survival. In contrast, preexisting and/or acquired mutations (in CDKN2A, YAP1, JAK2) correlate with innate resistance and/or tumor recurrence. Immunologically, tumor response after therapy entails T-cell receptor repertoire diversification in peripheral blood and intratumoral expansion of preexisting T-cell clones. A high ratio of regulatory to Th17 T cells in pretreatment blood predicts innate resistance, low cytolytic T-cell signature in pretreatment tumor, and low T-cell receptor repertoire diversity in pretreatment blood. Our study provides a molecular framework to advance neoadjuvant anti-PD-1 therapy for patients with resectable head-and-neck cancer.

2021-09-30 | GSE179730 | GEO

Immune suppressive landscape in a human esophageal squamous cell carcinoma microenvironment

Project description:Properly applying current immunotherapies or developing novel therapeutic strategies relies on a comprehensive understanding of the immune elements of the tumor microenvironment (TME). In this study, we aim to map at single-cell resolution the immune landscape of esophagus squamous cell carcinoma (ESCC), a common, aggressive, but understudied cancer of the gastrointestinal tract. We obtained a detailed immune cell atlas of the ESCC-associated transcriptome from a total of 80,787 tumor-infiltrating immune cells. Significant intertumoral heterogeneity was found among individual ESSC tumors. Exhausted T cells, exhausted NK cells, regulatory T cells, alternatively activated macrophages, and tolerogenic dendritic cells were discovered as the dominant portions of the immune cells in the TME. Dysfunctional T cells were the major proliferative cell compartment among tumor-infiltrating immune cells. In addition, strong potential interactions of immune cells in tumors may contribute to the immunosuppressive status and the progress of tumor development; a six-gene signature, comprising IFNGR1, IFNGR2, IDO1, IL10, CD163, and CD274, were associated with ESCC survival. Our results provided a comprehensive characterization of tumor-infiltrating immune cells in ESCC, indicating that immunosuppression of various kinds was synchronously responsible for the failure of immunosurveillance in ESCC. Specifically targeting the immunosuppressive pathways could reverse the immune-suppressive status and reactivate anti-tumor immune responses in ESCC.

2020-10-19 | GSE145370 | GEO

Targeting the MAtrix REgulating MOtif, MAREMO, abolishes hallmarks of cancer

Project description:Tumor targeted therapies have been largely inefficient due to lack of concomitant effects on the tumor microenvironment (TME). We investigated the MAtrix REgulating MOtif (MAREMO) mimicking peptide MP5, that inhibits the pro-tumorigenic extracellular matrix (ECM) molecule tenascin-C, using immunocompetent autologous breast cancer bearing mice. MP5 treatment led to tumor regression and reduced tumor cell dissemination. Several cancer hallmarks were abolished such as tumor cell promoting growth suppression and inhibition of plasticity enhancing responsiveness to death inducers. MP5 acts on other TME players leading to blood vessel normalization and depletion of fibroblasts diminishing the ECM as an orchestrator of immune suppression, causing immune cell infiltration and reactivation of anti-tumor immunity involving IFNgamma. Thus, targeting the tumor matrix using MAREMO in tenascin-C represents a powerful novel anti-cancer strategy.

2024-01-20 | E-MTAB-13677 | biostudies-arrayexpress

KDM1B is an important regulator of cytokine signaling in the tumor immune microenvironment and response to immune checkpoint therapy (RNA-seq)

Project description:Tumor microenvironment (TME) plays an important role in immune evasion and resistance to immune checkpoint therapy. Here, by using genetic, epigenetic, tumor biology and immunology approaches, we unraveled a key function of KDM1B in TME. KDM1B is important for maintaining several pro-oncogenic cytokine/chemokine signaling pathways. In vivo in resistant and inflammatory breast cancer models, ablation of KDM1B in tumor cells results in increased T cell activity and significantly improved response to anti-PD-1/anti-CTLA-4 therapy. Thus, this study identifies KDM1B as a key regulator of tumor immune microenvironment and offered the mechanistical basis for using KDM1B inhibitors in combinatory therapy to overcome resistance to immune checkpoint blockade.

2021-06-01 | GSE135400 | GEO

KDM1B is an important regulator of cytokine signaling in the tumor immune microenvironment and response to immune checkpoint therapy (ChIP-seq)

2021-06-01 | GSE135344 | GEO

Transcriptome comparison of PMN-MDSCs and and normal neutrophils

Project description:Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), also named pathologically activated neutrophil, is a critical component of tumor microenvironment (TME), playing crucial roles in tumor progression and therapy resistance. Here, we compared the transcriptome of PMN-MDSCs from B16 tumor bearing mice and the neutrophils from tumor free mice.

2023-06-26 | GSE199601 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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