Project description:The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors (ICI), such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. By functionally analyzing fecal metagenomes from 112 melanoma patients, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders. In an implanted tumor mouse model of anti-PD-1 treatment, microbiota-derived hexa-acylated LPS was required for effective anti-tumor immune responses, and LPS-binding antibiotics and a small molecule TLR4 antagonist abolished anti-PD-1 efficacy. Conversely, oral administration of hexa-acylated LPS to mice significantly augmented anti-PD-1-mediated anti-tumor immunity. Penta-acylated LPS did not improve anti-PD-1 efficacy in vivo and inhibited hexa-acylated LPS-induced immune activation in vitro. Microbiome hexa-acylated LPS therefore represents an accessible predictor and potential enhancer of immunotherapy responses.

2025-01-08 | MSV000096803 | MassIVE

E-ENAD-41

Project description:Regulation of gene expression in macrophage immune response

2020-04-22 | E-ENAD-41 | ExpressionAtlas

E-GEOD-39223

Project description:Regulation of gene expressions in vivo by anti-VEGF and anti-Notch therapy [HG-U133_Plus_2]

2025-01-24 | E-GEOD-39223 | ExpressionAtlas

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

E-GEOD-81046

Project description:Genetic ancestry and natural selection drive population differences in immune responses to pathogens in humans

2025-01-24 | E-GEOD-81046 | ExpressionAtlas

E-MTAB-8777

Project description:Selection of tumor resistant variants following sustained NK-mediated immune stress

2025-01-16 | E-MTAB-8777 | ExpressionAtlas

Genetic Analysis of Tumor Samples

Project description:<p>Antibody blockade of the inhibitory CTLA-4 pathway has led to clinical benefit in a subset of patients with metastatic melanoma. Anti-CTLA-4 enhances T cell responses, including production of IFN-γ, which is a critical cytokine for host immune responses. However, the role of IFN-γ signaling in tumor cells in the setting of anti-CTLA-4 therapy remains unknown. Here we demonstrate that, based upon exome sequencing data, patients identified as non-responders to anti-CTLA-4 (ipilimumab) harbor a much higher genomic defects in the IFN-γ pathway genes than melanoma patients who had clinical response to ipilimumab therapy.</p>

| phs001257 | dbGaP

E-ENAD-4

Project description:RNA-seq of 20 Triticum urartu accessions showing immune, hypersensitive reaction or susceptible responses to Bgt inoculation

2017-12-05 | E-ENAD-4 | ExpressionAtlas