Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade

ABSTRACT: Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade

PROVIDER: PRJNA1020891 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade

Project description:Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, homologous recombination (HR) status-dependent glycosylation has never been explored therapeutically. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe a unique enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8_ T cells. In orthotopic syngeneic EOC mouse models, inhibiting branched N-glycans, using 2-Deoxy-D-glucose, sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion

2024-03-11 | GSE244012 | GEO

Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade II

Project description:Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade II

| PRJNA1022481 | ENA

Targeting Glycomes Sensitizes Ovarian Tumors to Immune Checkpoint Blockade II

2024-09-29 | GSE244367 | GEO

Targeting branched N-glycans and fucosylation sensitizes ovarian tumors to immune checkpoint blockade.

Project description:Aberrant glycosylation is a crucial strategy employed by cancer cells to evade cellular immunity. However, it's unclear whether homologous recombination (HR) status-dependent glycosylation can be therapeutically explored. Here, we show that the inhibition of branched N-glycans sensitizes HR-proficient, but not HR-deficient, epithelial ovarian cancers (EOCs) to immune checkpoint blockade (ICB). In contrast to fucosylation whose inhibition sensitizes EOCs to anti-PD-L1 immunotherapy regardless of HR-status, we observe an enrichment of branched N-glycans on HR-proficient compared to HR-deficient EOCs. Mechanistically, BRCA1/2 transcriptionally promotes the expression of MGAT5, the enzyme responsible for catalyzing branched N-glycans. The branched N-glycans on HR-proficient tumors augment their resistance to anti-PD-L1 by enhancing its binding with PD-1 on CD8+ T cells. In orthotopic, syngeneic EOC models in female mice, inhibiting branched N-glycans using 2-Deoxy-D-glucose sensitizes HR-proficient, but not HR-deficient EOCs, to anti-PD-L1. These findings indicate branched N-glycans as promising therapeutic targets whose inhibition sensitizes HR-proficient EOCs to ICB by overcoming immune evasion.

| S-EPMC10987604 | biostudies-literature

IL-27 sensitizes immune checkpoint blockade therapy by inducing Treg fragility in high-grade serous ovarian cancer

Project description:IL-27 sensitizes immune checkpoint blockade therapy by inducing Treg fragility in high-grade serous ovarian cancer

| PRJNA866376 | ENA

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade

Project description:ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade

| PRJNA967357 | ENA

Immunogenic Chemotherapy Sensitizes Tumors to Checkpoint Blockade Therapy.

Project description:Checkpoint blockade immunotherapies can be extraordinarily effective, but might benefit only the minority of patients whose tumors are pre-infiltrated by T cells. Here, using lung adenocarcinoma mouse models, including genetic models, we show that autochthonous tumors that lacked T cell infiltration and resisted current treatment options could be successfully sensitized to host antitumor T cell immunity when appropriately selected immunogenic drugs (e.g., oxaliplatin combined with cyclophosphamide for treatment against tumors expressing oncogenic Kras and lacking Trp53) were used. The antitumor response was triggered by direct drug actions on tumor cells, relied on innate immune sensing through toll-like receptor 4 signaling, and ultimately depended on CD8(+) T cell antitumor immunity. Furthermore, instigating tumor infiltration by T cells sensitized tumors to checkpoint inhibition and controlled cancer durably. These findings indicate that the proportion of cancers responding to checkpoint therapy can be feasibly and substantially expanded by combining checkpoint blockade with immunogenic drugs.

| S-EPMC4758865 | biostudies-literature

Enhanced efficacy of simultaneous PD-1 and PD-L1 immune checkpoint blockade in high grade serous ovarian cancer [ATAC-seq]

Project description:Immune therapies have had limited efficacy in high grade serous ovarian cancer (HGSC). The cellular targets and mechanism(s) of action of these agents in HGSC are unknown. Here we performed immune functional and single cell RNA sequencing transcriptional profiling on novel HGSC organoid/immune cell co-cultures treated with a variety of immune checkpoint blockade (ICB) antibodies compared to controls.

2020-11-04 | GSE160750 | GEO

Enhanced efficacy of simultaneous PD-1 and PD-L1 immune checkpoint blockade in high grade serous ovarian cancer [bulk RNA-seq tumor]

2020-11-04 | GSE160751 | GEO

Enhanced efficacy of simultaneous PD-1 and PD-L1 immune checkpoint blockade in high grade serous ovarian cancer [single-cell RNA-seq tumor]

2020-11-04 | GSE160754 | GEO