Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Intratumoral plasmid IL-12 expands CD8+ T cells and induces a CXCR3 signature in triple-negative breast tumors that sensitizes patient to anti-PD-1 therapy

ABSTRACT: We show that plasmid IL-12 injected intratumorally followed by co-localized electroporation induces a CXCR3 gene signature with enhanced antigen presentation, expansion, and licensing of T cells systemically. We highlight a patient that was previously non-responsive to atezolizumab and nab-paclitaxel, who demonstrated significant clinical response to nivolumab following TAVOTM therapy.

ORGANISM(S): Mus musculus

PROVIDER: GSE157819 | GEO | 2021/09/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Distinct Cellular Mechanisms Underlie Chemotherapies and Their Combinations with PD-L1 Checkpoint Inhibitor in Triple-Negative Breast Cancer [TNBC]

Project description:The combination of immune checkpoint blockade (ICB) and chemotherapy holds promise for treating triple-negative breast cancer (TNBC), yet the underlying mechanisms remain incompletely understood. Here, we integrated previously published and newly generated single-cell RNA sequencing (scRNA-seq) data to investigate the tumor immune microenvironment (TIME) in advanced TNBC patients receiving various therapies, including paclitaxel, nab-paclitaxel, and their combinations with an anti-PD-L1 antibody atezolizumab. Notably, compared to atezolizumab plus paclitaxel, atezolizumab plus nab-paclitaxel primarily rewired TCF7+ stem-like effector memory CD8 T cells (Tsem) and CD4 follicular helper T (Tfh) cells. Nab-paclitaxel, but not paclitaxel, predominantly modulated the myeloid compartment, expanding mast cells and pro-inflammatory macrophage subsets. Our analyses in human TNBC and murine models highlighted the crucial role of mast cells in orchestrating anti-tumor immune responses, likely by recruiting and activating T cells and B cells. In vivo experiments demonstrated that activating mast cells alongside PD-L1 blockade significantly attenuated tumor progression, suggesting mast cells as a promising adjunct for enhancing ICB therapy efficacy.

2025-02-12 | GSE266919 | GEO

Intratumoral Plasmid IL12 Expands CD8<sup>+</sup> T Cells and Induces a CXCR3 Gene Signature in Triple-negative Breast Tumors that Sensitizes Patients to Anti-PD-1 Therapy.

Project description:PurposeTriple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Antibodies targeting programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) have entered the therapeutic landscape in TNBC, but only a minority of patients benefit. A way to reliably enhance immunogenicity, T-cell infiltration, and predict responsiveness is critically needed.Patients and methodsUsing mouse models of TNBC, we evaluate immune activation and tumor targeting of intratumoral IL12 plasmid followed by electroporation (tavokinogene telseplasmid; Tavo). We further present a single-arm, prospective clinical trial of Tavo monotherapy in patients with treatment refractory, advanced TNBC (OMS-I140). Finally, we expand these findings using publicly available breast cancer and melanoma datasets.ResultsSingle-cell RNA sequencing of murine tumors identified a CXCR3 gene signature (CXCR3-GS) following Tavo treatment associated with enhanced antigen presentation, T-cell infiltration and expansion, and PD-1/PD-L1 expression. Assessment of pretreatment and posttreatment tissue from patients confirms enrichment of this CXCR3-GS in tumors from patients that exhibited an enhancement of CD8+ T-cell infiltration following treatment. One patient, previously unresponsive to anti-PD-L1 therapy, but who exhibited an increased CXCR3-GS after Tavo treatment, went on to receive additional anti-PD-1 therapy as their immediate next treatment after OMS-I140, and demonstrated a significant clinical response.ConclusionsThese data show a safe, effective intratumoral therapy that can enhance antigen presentation and recruit CD8 T cells, which are required for the antitumor efficacy. We identify a Tavo treatment-related gene signature associated with improved outcomes and conversion of nonresponsive tumors, potentially even beyond TNBC.

| S-EPMC8102331 | biostudies-literature

Amplification of the CXCR3/CXCL9 axis via intratumoral electroporation of plasmid CXCL9 synergizes with plasmid IL-12 therapy to elicit robust anti-tumor immunity.

Project description:Clinical studies have demonstrated that local expression of the cytokine IL-12 drives interferon-gamma expression and recruits T cells to the tumor microenvironment, ultimately yielding durable systemic T cell responses. Interrogation of longitudinal biomarker data from our late-stage melanoma trials identified a significant on-treatment increase of intratumoral CXCR3 transcripts that was restricted to responding patients, underscoring the clinical relevance of tumor-infiltrating CXCR3+ immune cells. In this study, we sought to understand if the addition of DNA-encodable CXCL9 could augment the anti-tumor immune responses driven by intratumoral IL-12. We show that localized IL-12 and CXCL9 treatment reshapes the tumor microenvironment to promote dendritic cell licensing and CD8+ T cell activation. Additionally, this combination treatment results in a significant abscopal anti-tumor response and provides a concomitant benefit to anti-PD-1 therapies. Collectively, these data demonstrate that a functional tumoral CXCR3/CXCL9 axis is critical for IL-12 anti-tumor efficacy. Furthermore, restoring or amplifying the CXCL9 gradient in the tumors via intratumoral electroporation of plasmid CXCL9 can not only result in efficient trafficking of cytotoxic CD8+ T cells into the tumor but can also reshape the microenvironment to promote systemic immune response.

| S-EPMC9092072 | biostudies-literature

PD-1 Blockade Expands Intratumoral Memory T Cells.

Project description:Tumor responses to programmed cell death protein 1 (PD-1) blockade therapy are mediated by T cells, which we characterized in 102 tumor biopsies obtained from 53 patients treated with pembrolizumab, an antibody to PD-1. Biopsies were dissociated, and single-cell infiltrates were analyzed by multicolor flow cytometry using two computational approaches to resolve the leukocyte phenotypes at the single-cell level. There was a statistically significant increase in the frequency of T cells in patients who responded to therapy. The frequency of intratumoral B cells and monocytic myeloid-derived suppressor cells significantly increased in patients' biopsies taken on treatment. The percentage of cells with a regulatory T-cell phenotype, monocytes, and natural killer cells did not change while on PD-1 blockade therapy. CD8(+) memory T cells were the most prominent phenotype that expanded intratumorally on therapy. However, the frequency of CD4(+) effector memory T cells significantly decreased on treatment, whereas CD4(+) effector T cells significantly increased in nonresponding tumors on therapy. In peripheral blood, an unusual population of blood cells expressing CD56 was detected in two patients with regressing melanoma. In conclusion, PD-1 blockade increases the frequency of T cells, B cells, and myeloid-derived suppressor cells in tumors, with the CD8(+) effector memory T-cell subset being the major T-cell phenotype expanded in patients with a response to therapy.

| S-EPMC4775381 | biostudies-literature

T1 aptamer targets intratumoral myeloid cells with immunosuppression functions

Project description:Intratumorally, immunosuppressive myeloid subsets are difficult to distinguish from mature, non-suppressive counterparts. T1 aptamer specifically targets the former subset and was used here to isolated the subsets for transcriptomic profiling.

2021-11-24 | GSE185974 | GEO

Study to evaluate the effect of intratumoral heterogeneity on gene expression measurements

Project description:To evaluate the effect of intratumorally heterogeneity on gene expression measurements, we profiled and compared samples from different macroscopic tumor areas. Information was used to select probe sets with a high spatial reproducibility for the development of gene signatures.

2019-05-30 | GSE129557 | GEO

Neoadjuvant BMS-813160, nivolumab, gemcitabine and nab-paclitaxel for pancreatic cancer

Project description:Neoadjuvant BMS-813160, nivolumab, gemcitabine and nab-paclitaxel for pancreatic cancer

| PRJNA1218232 | ENA

Transcriptomic analysis of mouse subcutaneous tumor after intratumoral treatment with SLR14 or vehicle

Project description:We subcutaneously injected 5x105 YUMMER1.7 melanoma into right flank of C57BL/6J mice. 7 days later, the mice were intratumorally treated with 1 mg/kg SLR14 or vehicle every 3 days, for a total of 3 cycles. We observed a significant tumor growth delay in SLR14-treated mice compared to vehicle-treated mice.

2019-09-07 | GSE136995 | GEO

Small IncQ1 Plasmid Encoding KPC-2 Expands to Invasive Nontyphoidal Salmonella.

Project description: Not available

| S-EPMC8522750 | biostudies-literature

A Study of CM24 in Combination With Nivolumab in Adults With Advanced Solid Tumors

Project description:This is an open-label, multicenter, multi-dose escalation and dose expansion study in subjects with selected advanced solid tumors (Part A) and advanced metastatic pancreatic cancer (Parts C & D) to evaluate the safety and tolerability of CM-24 in combination with nivolumab. In Part C of the study gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV will be administered subsequent to CM24 and nivolumab. CM24, nivolumab and gemcitabine/nab-paclitaxel or Nal-IRI/5-FU/LV are administered intravenously.

| 2365595 | ecrin-mdr-crc

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