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Systemic blockade of Clever-1 in patients with solid tumours elicits lymphocyte activation alongside checkpoint molecule downregulation

ABSTRACT: Systemic blockade of Clever-1 in patients with solid tumours elicits lymphocyte activation alongside checkpoint molecule downregulation

PROVIDER: PRJNA638546 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11973449.fastq.gz	Fastqsanger.gz
	SRR11973450.fastq.gz	Fastqsanger.gz
	SRR11973451.fastq.gz	Fastqsanger.gz
	SRR11973452.fastq.gz	Fastqsanger.gz
	SRR11973453.fastq.gz	Fastqsanger.gz

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Similar Datasets

Systemic blockade of Clever-1 in patients with solid tumours elicits lymphocyte activation alongside checkpoint molecule downregulation

Project description:Macrophages are critical in driving an immunosuppressive tumour microenvironment that counteracts the efficacy of T-cell targeting therapies1. Thus agents, which can re-programme macrophages towards a pro-inflammatory state hold promise as novel immunotherapies for solid cancers2. Here we report that therapeutic targeting of a macrophage scavenger receptor, Clever-13, in heavily pre-treated metastatic cancer patients was able to induce a significant increase and activation of peripheral T-cells including downregulation of several immune checkpoint molecules. Transcriptional and mass cytometry analyses revealed treatment induced inflammatory conversion of blood monocytes, which was partly driven by impaired Clever-1 mediated scavenging. Identification of relevant peripheral signatures indicative of anti-tumour activity showed induction of an effector CD8 T-cell population that resulted from clonal expansion of cytotoxic CD8 T-cells. In some patients this was accompanied by features of increased accumulation of CD8 T-cells in post-treatment tumour biopsies. Our results reveal a non-redundant role played by the receptor Clever-1 in suppressing adaptive immune cell activation in humans. We provide evidence that targeting macrophage scavenging activity can promote an immune switch leading to peripheral activation and potentially intra tumoural proinflammatory responses in metastatic cancer patients. Anti-Clever-1 treatment may therefore provide an attractive immunotherapeutic strategy in cancer.

2022-05-22 | GSE152169 | GEO

Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I/II Clinical Trial.

Project description: Not available

| S-EPMC9401456 | biostudies-literature

Gene expression analysis of human CD14+ monocytes after anti-Clever-1 treatment

Project description:Clever-1 is a scavenger receptor expressed on a subset of immunosuppressive macrophages and monocytes. We analyzed the gene expression profiles of CD14+ monocytes isolated from cancer patients treated with a humanized anti-Clever-1 antibody (FP-1305) in a phase I/II clinical trial (MATINS; NCT03733990) to understand how anti-Clever-1 treatment changes the phenotype and activation of circulating monocytes.

2021-06-03 | GSE151085 | GEO

Claudication: Exercise Versus Endoluminal Revascularization (CLEVER-BioLINCC)

Project description:Claudication: Exercise Versus Endoluminal Revascularization (CLEVER-BioLINCC)

| PRJNA1499230 | ENA

Claudication: Exercise Versus Endoluminal Revascularization (CLEVER-BioLINCC)

Project description:Claudication: Exercise Versus Endoluminal Revascularization (CLEVER-BioLINCC)

| PRJNA1499232 | ENA

KP lung tumours

Project description:KP lung tumours

| PRJNA577056 | ENA

Transcriptional Profiling of Mouse Tumours

Project description:Transcriptional Profiling of Mouse Tumours

| PRJNA905435 | ENA

Gene expression analysis of human CD14+ monocytes after anti-Clever-1 treatment

Project description:Gene expression analysis of human CD14+ monocytes after anti-Clever-1 treatment

| PRJNA634560 | ENA

Bladder Tumours O-Glycoproteomics

Project description:Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation. These include the presence of short chain O-glycans such as Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST). The presence of such structures is commonly associated with poor prognosis. In search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for these short-chain O-glycans. Aiming at identifying protein targets, we have studied the O-glycoproteome of a pool of STn positive tumours from muscle invasive bladder cancer (MIBC) patients.

2017-08-17 | PXD006813 | Pride

Maffucci tumours

Project description:This SuperSeries is composed of the following subset Series: GSE26667: Expression array using Maffucci tumours GSE26674: SNP array analysis on Maffucci tumours Refer to individual Series

2011-07-18 | E-GEOD-26675 | biostudies-arrayexpress

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