Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PD1 Antibody Toripalimab and Chemoradiotherapy for dMMR/MSI-H Locally Advanced Colorectal Cancer

ABSTRACT: PD1 antibody is now recommended for dMMR/MSI-H metastatic colorectal cancer patients as second line. Chemoradiotherapy is standand treatment for locally advanced rectal cancer and is also recommended as an alternative choice for unresectable locally advanced colon cancer. Thus, this study will investigate the efficacy and toxicity of combination strategy using PD1 antibody and chemoradiotherapy for dMMR/MSI-H locally advnaced colorectal cancer patients.

DISEASE(S): Dmmr Colorectal Cancer,Locally Advanced Colorectal Cancer,Colorectal Neoplasms,Msi-h Colorectal Cancer

PROVIDER: 2332565 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Pd1 Antibody Sintilimab ± Chemoradiotherapy for Locally Advanced Rectal Cancer

Project description:In this study, participants with locally advanced rectal cancer patients will be treated according to MMR/MSI status. There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, dMMR or MSI-H patients will receive 4 cycles of neoadjuvant Pd1 antibody Sintilimab,followed by one of the following treatments: (1) surgery and adjuvant treatment, (2）another 4 cycles of sintilimab, followed by radical surgery or observation (only for cCR) . For Cohort B, pMMR/MSS/MSI-L patients will be randomized to receive neoadjuvant chemoradiotherapy ± four cycles of Pd1 antibody Sintilimab，followed by one of the following treatments: (1) curative surgery and four cycles of adjuvant chemotherapy;(2)four cycles of chemotherapy then observation (only cCR after neoadjuvant therapy)

| 2332769 | ecrin-mdr-crc

Hypermethylation and downregulation of UTP6 are associated with stemness properties, chemoradiotherapy resistance and prognosis in rectal cancer: A co-expression network analysis

Project description:To measure global gene expression in primary locally advanced rectal cancer patients who have undergone CRT and screen valuable biomarkers to predict the effects of CRT.Samples fromprimary locally advanced rectal cancer patients were collected. The effects of chemoradiotherapy were evaluated.

2021-06-04 | GSE145037 | GEO

miRNA expression between CD4+PD1+ and CD4+PD1- T cells

Project description:Recent success in cancer immunotherapy has come from the blockade of inhibitory receptors on T cells, such as programmed cell death-1, which can induce a state of T cell exhaustion upon constant antigen stimulation. Understanding miRNA regulation of PD1 can be useful to discover miRNAs for use in therapy or as prognostic markers in various diseases including cancer, autoimmunity and transplantation. We used microarrays to discover global miRNA expression changes upon PD1 upregulation and identified miRNAs that are both up- and down-regulated. B16F10 cells were injected subcutaneously into C57BL/6 mice and 16 days later CD4+PD1+ and CD4+PD1- were sorted from the lymph nodes and spleen for RNA extraction and hybridization on Affymetrix miRNA array.

2015-08-01 | E-GEOD-65208 | biostudies-arrayexpress

Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [RNA-sequencing]

Project description:Approximately 15% of colorectal cancer (CRC) patients present with high levels of microsatellite instability (MSI-H), which is driven by defective mismatch repair (dMMR). While about 20% of MSI-H tumors are associated with the hereditary condition, Lynch syndrome (LS), the majority develop through non-hereditary mechanisms. In recent years, the molecular processes underpinning tumor development in LS patients has been debated, with the longstanding view that dMMR is a secondary process in CRC development of LS patients being questioned. Here, we performed the first multi-omic analysis of normal colon organoids developed from LS and healthy patients to address questions regarding the development of dMMR in LS colon epithelial cells from cancer-free individuals.

2023-06-01 | GSE211221 | GEO

Multi-omic colon organoid analysis highlight MSH4 as a marker of Lynch syndrome and microsatellite instability [methylation array]

2023-06-01 | GSE210018 | GEO

Total RNA from cell lines (JurkatLAG+PD1+ and Raji-PDL1) treated with anti-PD1 antibody (MK3475) and/ or anti-LAG3 antibody (MK4280) was sequenced.

Project description:A previously established bioassay using Jurkat cells overexpressing PD1 and Lag3 allowed for assessment of simultaneous blockade of PD1 and LAG3 pathways in an in-vitro setting and demonstrated that an antibody cocktail increased IL-2 levels 5-fold better than single agent treatment. To gain understanding of signal transduction events RNA-Seq analysis of cell pellets individually treated with LAG3 or PD1 antibodies was used to reveal modest immune activation however, 5-fold more genes were upregulated upon combination treatment. There were increases in costimulatory genes like CD28, CD5, CD6 as well as other intracellular signaling molecules like LCP2 and ITK. Given the role of ERK in immune activation of T cells, pERK levels of Jurkat cells in the assay were evaluated, indicating that ERK phosphorylation was impacted on PD1 and LAG3 engagement with their ligands and this could be reversed by antibody blockade. A small molecule phosphatase inhibitor NSC87877, when combined with the PD1 antibody, could phenocopy the effect of combining PD1 and LAG3 blocking antibodies. CD28 has a recognized role in PD1 signaling but the impact on LAG3 signaling remains unknown. CD28 knockout cells demonstrated an overall muted IL-2 response but retained combination benefit in terms of IL-2 production in the context of LAG3 and PD1 co-blockade versus individual antibody treatments. Taken together, these observations provide new insights on the impact of LAG3 and PD1 co-blockade and provides additional support for ongoing immunotherapy clinical trials that combine PD1 and LAG3 antibodies.

2023-07-29 | GSE201871 | GEO

Dickkopf 1 Impairs Sensitivity to PD-1 Blockade through CD8+ T Cell Inactivation in dMMR/MSI Colorectal Cancer

Project description:Dickkopf 1 (DKK1) could promote tumor progression by suppressing immunity. Therefore, we investigated whether DKK1 influence prognosis and sensitivity to PD-1 blockade in colorectal cancers (CRCs) with defective DNA mismatch repair genes (dMMR) or microsatellite instability (MSI). We found that elevated DKK1 expression was associated with recurrence and dismissed CD8+ T cell infiltrations, and patients with high serum DKK1 had poor anti-PD-1 response. RNA interference or neutralization of DKK1 in CRCs enhanced CD8+ T cell cytotoxicity, and down-regulation of T-bet and E2F1 following GSK3β activation was detected in DKK1-treated CD8+ T cells. In organoid-lymphocyte co-culture model, apoptosis proportions were elevated after individual neutralization of both PD-1 and DKK1, and the combined neutralization resulted in further increases. In conclusion, DKK1 suppresses tumor immunity in dMMR/MSI CRCs by inactivating CD8+ T cells through GSK3β/E2F1/T-bet axis. DKK1 neutralization may improve the sensitivity to PD-1 blockade in dMMR/MSI CRCs.

2021-04-07 | GSE149206 | GEO

Envolimab Monotherapy or Envolimab + CAPEOX as Neoadjuvant Therapy for Locally Advanced Colorectal Cancer

Project description:There exists substantial evidence suggesting that patients diagnosed with MSI-H/dMMR colorectal cancer can derive benefits from immunotherapy in the management of advanced colorectal cancer. In cases of locally advanced colorectal cancer exhibiting microsatellite instability (dMMR/MSI-H), patients exhibit low responsiveness to neoadjuvant chemotherapy, resulting in minimal rates of complete tumor remission and downstaging. Nevertheless, initial exploratory studies, characterized by modest sample sizes, reveal a favorable therapeutic effect of neoadjuvant immunotherapy in this particular patient population. Envality monoclonal antibody, the first PD-L1 antibody developed and manufactured in China, possesses noteworthy practical and societal value in the context of exploratory clinical research on neoadjuvant immunotherapy for locally advanced MSI-H/dMMR colorectal cancer patients. The objective of this study is to evaluate the safety and efficacy of Envality monoclonal antibody (PD-L1) as neoadjuvant therapy for locally advanced MSI-H/dMMR colorectal cancer through a prospective, multi-cohort phase II clinical trial. Additionally, this study aims to investigate the effectiveness and safety of Envality monoclonal antibody in combination with CAPEOX as a neoadjuvant treatment regimen for locally advanced pMMR colorectal cancer.

| 90202 | ecrin-mdr-crc

Nivolumab and Ipilimumab in Patients With dMMR and/or MSI Metastatic Colorectal Cancer Resistant to Anti-PD1 Monotherapy

Project description:NIPIRESCUE is a national, single-arm, open-label phase II study. The study aims to evaluate the clinical activity of nivolumab and ipilimumab in patients with MSI/dMMR mCRC resistant to anti-PD1 monotherapy and previously treated with fluoropyrimidine, oxaliplatine, irinotecan, and anti- vascular endothelial growth factor (VEGF) or anti- epidermal growth factor receptor (EGFR) therapy.

| 2717352 | ecrin-mdr-crc

PD1 inhibits PKCθ-dependent phosphorylation of cytoskeleton-related proteins and immune synapse formation

Project description:The cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. An improved understanding of intracellular pathways targeted by PD1 is needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering reduces the phosphorylation and physical association with PKC theta of a variety of cytoskeletal proteins. TCR-induced phosphorylation of Vimentin, a cytoskeleton protein identified as a PKC theta target and binding partner in our study, was found to be long-lasting and durably inhibited by PD1 triggering, and Vimentin phosphorylation inversely correlated with PDL1 levels in intratumoral T cells in human lung carcinoma. Thus, PKCθ and its substrate Vimentin represent important targets of PD1-mediated T cell inhibition and low levels of Vimentin phosphorylation could be considered as a biomarker indicating PD1 pathway engagement.

2024-04-19 | PXD044028 | Pride

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