Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Chemohormonal Therapy Remodels Prostate Cancer Immune Microenvironment and Enhances Checkpoint Inhibitor-based immunotherapy

ABSTRACT: Checkpoint blockade immunotherapy is a promising strategy in cancer treatment, depending on a favorable preexisting tumor immune microenvironment. However, prostate cancer is usually considered as an immune “cold” tumor with the poor immunogenic response and low density of tumor-infiltrating immune cells. This research uses samples from prostate cancer patients showing that docetaxel-based chemohormonal therapy reprograms the immune microenvironment and increases tumor-infiltrating T cells. Mechanistically, docetaxel treatment activates the cGAS/STING pathway and induces the type I interferon signaling, which may boost T cell-mediated immune response. In a murine prostate cancer model, chemohormonal therapy sensitizes tumor-bearing mice to PD1-blockade therapy. These findings demonstrate that docetaxel-based chemohormonal therapy activates prostate cancer immunogenicity and acts cooperatively with anti-PD-1 checkpoint blockade, providing a combination immunotherapy strategy that would lead to better therapeutic benefit for prostate cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193898 | GEO | 2022/08/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

scRNA-seq analysis demonstrate alterations in TICs of the TME during TREM1 inhibition and anti-PD-1 treatment in B16F10 melanoma

Project description:To comprehensively characterize the changes within the TME during TREM1 deficiency and anti-PD-1 immune checkpoint blockade therapy, we performed scRNA-seq analysis of the CD45+ TICs in melanoma-bearing C57BL/6 mice receiving the various treatments. We analyzed approximately 8,249 CD45+ cells from the treatment groups with t-SNE analysis, identifying 10 distinct clusters of tumor-infiltrating immune cells

2023-09-27 | E-MTAB-13300 | biostudies-arrayexpress

Tumor cell intrinsic type I interferon signaling dictates CD47-SIRPα blockade immunotherapy via metabolic reprograming [dataset 1]

Project description:Innate immune checkpoint has emerging as a highly potential target for cancer immunotherapy in recent years. The CD47-SIRPα axis is the best-studied innate checkpoint in cancer. However, the transcription profile of tumor cell duiring CD47-SIRPα blockade therapy remains unclear.

2024-06-04 | GSE235111 | GEO

Tissue-resident Memory and Circulating T cells are Early Responders to Pre-surgical Cancer Immunotherapy

Project description:Pre-surgical (neoadjuvant) immune checkpoint blockade has shown promising activity in multiple cancer types, but the molecular mechanisms are not well understood. Here, we characterized early kinetic changes in tumor-infiltrating and circulating immune cells in oral cancer patients treated with neoadjuvant anti-PD-1 or anti-PD-1/CTLA-4 in a phase 2 clinical trial. Tumor-infiltrating CD8 T cells that clonally expanded during immunotherapy expressed elevated tissue-resident memory and cytotoxicity programs compared to non-responding cells. These programs were already active in pre-treatment T cells that later responded, reflecting a capacity for rapid response. Treatment also induced a systemic immune response, including expansion of pre-existing and emergent T cell clonotypes undetectable prior to therapy. The frequency of activated blood CD8 T cells, including pretreatment PD-1-positive KLRG1-negative T cells, was strongly associated with intra-tumoral pathological response, and these activated cells were enriched for tumor-infiltrating T cell clonotypes. These results demonstrate how neoadjuvant checkpoint blockade induces local and systemic tumor immunity.

2022-07-07 | GSE200996 | GEO

Tumor immunological phenotype signature-based high-throughput screening for the discovery of combination immunotherapy compounds

Project description:Immune checkpoint blockade (ICB) therapy intends to only benefit a fraction of cancer patients, and combination immunotherapy with a compound is a promising treatment to overcome this limitation. Here, a tumor immunological phenotype (TIP) gene signature and high throughput sequencing-based high throughput screening (HTS2) were combined to identify combination immunotherapy compounds. We firstly defined a TIP gene signature, which expression pattern distinguishes “cold” tumors from “hot” tumors, and predicts ICB response in cancer patients. Then, after screening thousands of compounds, we identified that aurora kinase inhibitors, including ENMD-2076 and TAK-901, could reprogram the expression pattern of TIP genes from “cold” tumor to “hot” tumor in triple negative breast cancer (TNBC) cells. The treatment of aurora kinase inhibitors on TNBC cells dramatically up-regulates expression of Th1 type chemokine genes CXCL10 and CXCL11, which promotes effective T cells infiltrating into tumor microenvironment and significantly improves anti-PD-1 efficacy in inhibiting the tumor growth of TNBC in preclinical models. Mechanistically, these aurora kinase inhibitors are mainly through inhibiting AURKA-STAT3 signaling pathway to stimulate the expression of CXCL10 and CXCL11. Our study established a high throughput strategy to discover candidate compounds for combination immunotherapy, and suggested the therapeutic potential of combining aurora kinase inhibitors with checkpoint blockade immunotherapy for the treatment of TNBC.

2020-12-31 | GSE160071 | GEO

A single cell atlas of tumor resistance to PD-1 blockade and radiotherapy: Bulk Tumor RNA Sequencing

Project description:Abstract: Transplanted tumors in syngeneic mice treated with immune checkpoint blockade and radiotherapy demonstrate synergy and an abscopal effect. Indeed, tumors generated from sarcoma cell lines transplanted into syngeneic mice are cured by PD-1 blockade and radiotherapy, but autochthonous, primary sarcomas from the same high mutational load model are resistant to the identical treatment. Here, we generated a single cell atlas of tumor-infiltrating immune cells from allograft and primary tumors, which demonstrates marked differences in their immune landscapes before and after radiation and immunotherapy. Allograft tumors are enriched for effector CD8+ T cells that mediate response to combination therapy, but the immune response to primary sarcomas shows tumor-specific tolerance. Genetic barcoding of primary tumors reveals a cellular response to combination therapy, but resistance of specific clones. Together, this comprehensive comparison of the primary and allograft tumor microenvironments identifies immune tolerance and clonal resistance to immunotherapy and radiotherapy specific to primary tumors.

2020-03-10 | GSE134273 | GEO

SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion

Project description:Although genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 relieves endogenous DNA damage and suppresses cGAS-STING-dependent immune signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a transcriptional regulatory element in the PD-L1 gene, thereby promoting PD-L1 expression in cancer cells. Loss of SMARCAL1 enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a valuable target for cancer immunotherapy.

2024-01-24 | PXD046384 | Pride

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade [WES]

Project description:Immune checkpoint blockade is able to achieve durable responses in a subset of patients, however we lack a satisfying comprehension of the underlying mechanisms of anti-CTLA-4 and anti-PD-1 induced tumor rejection. To address these issues we utilized mass cytometry to comprehensively profile the effects of checkpoint blockade on tumor immune infiltrates in human melanoma and murine tumor models. These analyses reveal a spectrum of tumor infiltrating T cell populations that are highly similar between tumor models and indicate that checkpoint blockade targets only specific subsets of tumor infiltrating T cell populations. Anti-PD-1 predominantly induces the expansion of specific tumor infiltrating exhausted-like CD8 T cell subsets. In contrast, anti-CTLA-4 induces the expansion of an ICOS+ Th1-like CD4 effector population in addition to engaging specific subsets of exhausted-like CD8 T cells. Thus, our findings indicate that anti-CTLA-4 and anti-PD-1 checkpoint blockade induced immune responses are driven by distinct cellular mechanisms.

2017-08-10 | GSE100808 | GEO

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade [RNA-seq]

2017-08-10 | GSE100807 | GEO

Treating ICB-resistant glioma with anti-CD40 and mitotic spindle checkpoint controller BAL101553 (lisavanbulin)

Project description:drugs targeting mitosis might affect the tumor microenvironment and sensitize cancer cells to immunotherapy. BAL101553 monotherapy increased survival in immune checkpoint blockade–resistant SB28 glioblastoma tumors and synergized with anti-CD40 antibody

2021-10-23 | GSE186302 | GEO

Radiation Therapy Inhances Immunotherapy Response in Microsatellite-stable Colorectal and Pancreatic Adenocarcinoma in a Phase II Trial

Project description:Immune checkpoint blockade has limited efficacy in microsatellite stable (MSS) colorectal (CRC) and pancreatic (PDAC) cancer. Preclinical models have demonstrated the use of radiation to activate the innate immune response and stimulate responsiveness to immune checkpoint blockade. Here, we describe a Phase 2 trial of radiation therapy combined with combined anti-CTLA4 (ipilimumab) and anti-PD1 (nivolumab) antibodies in MSS CRC and PDAC. In the per protocol analysis disease control rate was 37% (10/27) in CRC and 29% (5/17) in PDAC with an overall response rate of 15% (4/27) and 18% (3/17), respectively. Whole exome and RNA sequencing of biopsies from 17 patients revealed low tumor mutational burden in all tumors, but a notable upregulation of interferon stimulated genes with concordant high expression of multiple repeat RNA transcripts in responders. Altogether, this study provides foundational human proof of concept of radiation with combination immune checkpoint blockade therapy in otherwise immunotherapy resistant cancers.

2021-07-06 | GSE179351 | 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