Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA171428 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:<p>The effectiveness of immunotherapy varies among patients with advanced non-small cell lung cancer (NSCLC). Here we investigated the baseline immune status in stage IV NSCLC patients treated with anti-PD-1 plus chemotherapy to understand the immune mechanisms and unveil systemic markers associated with treatment response. Responders had elevated frequencies of circulating T cells expressing CD69, TCF-1 and CXCR-3. In contrast, non-responders presented increased frequencies of CTLA-4, CD161 and IL-10 expressing CD4+ and CD8+ T cells. These systemic T cell immune profiles were mirrored in the tumor microenvironment of an independent cohort. Concurrent CTLA-4 and PD-1 blockade was able to reactivate an anti-tumor profile in T cells from non-responder patients, emphasizing the pivotal role of CTLA-4 in contributing to an immunosuppressive environment that hinders effective treatment in NSCLC. This work supports the implementation of personalized immunotherapies based on systemic immune biomarkers, offering a promising approach to enhance treatment outcomes in advanced NSCLC.</p>
2025-10-16 | MTBLS13150 | MetaboLights
Project description:Immune checkpoint inhibitors (CPIs) have revolutionised cancer treatment, with previously untreatable disease now amenable to potential cure. Combination regimens of anti-CTLA-4 and anti-PD-1 show enhanced efficacy but are prone to off-target immune-mediated tissue injury, particularly at the barrier surfaces. CPI-induced colitis is a common and serious complication. A higher proportion of patients undergoing monotherapy anti-CTLA-4 treatment tend to develop colitis compared to monotherapy treated anti-PD-1 treated patients. This effect is enhanced when patients are treated with both drugs. To probe the impact of either anti-CTLA4 or anti-PD1 on intestinal homeostasis, mice were challenged with anti-CTLA-4 and anti-PD-1 immunotherapy in either monotherapy or together in combination. Manipulation of the intestinal microbiota has also been shown to be important in both this model, from previous data, and in patients. Colonic immune responses were then profiled using bulk RNA-sequencing.
2023-09-08 | GSE241664 | GEO
Project description:Human fecal WMS data from patients treated with combined anti-CTLA-4 and anti-PD-1 immunotherapy for advanced melanoma.
| EGAD00001006734 | EGA
Project description:Immunotherapy has transformed the landscape of cancer treatment but remains largely ineffective for patients with pancreatic ductal adenocarcinoma (PDAC). Some patients, however, show improved outcomes when treated with a combination of immunotherapy and chemotherapy. Here, we conducted deep serum proteome analysis to investigate the protein profiles of PDAC patients and changes during this combinatorial treatment. Utilizing an advanced serum workflow, we quantified 1,011 proteins across 211 samples from 62 patients. Glycolytic enzymes were associated with survival in anti-PD-1 treated patients, with their abundances significantly correlating with expression levels in tumor biopsies. Notably, a set of protein biomarkers was found to be highly predictive of survival in anti-PD-1-treated patients (AUC = 0.91). Overall, our data demonstrate the potential of deep serum proteomics for precision medicine, offering a powerful tool to guide patient selection for treatment through minimally invasive serum protein biomarker measurements.
2024-06-19 | MSV000095077 | MassIVE
Project description:Human fecal 16S rRNA gene sequencing data from patients treated with combined anti-CTLA-4 and anti-PD-1 immunotherapy for advanced melanoma.
| EGAD00001006735 | EGA
Project description:Predictors of immune checkpoint inhibitor response in cancer remain elusive. From a previous phase 2 neoadjuvant immunotherapy window-of-opportunity study, we present the single-cell RNA and T cell receptor (TCR) sequencing analysis of 57 pre- and post-treatment tumor biopsies from head and neck cancer patients treated with durvalumab (anti-PD-L1) alone or with tremelimumab (anti-CTLA-4), identifying key cellular and molecular predictors of immune checkpoint inhibitor (ICI) response. Malignant cells and neutrophil senescence promote ICI response. While CXCL13+ exhausted T (Tex) cells enhance response through 4-1BB signaling, anti-CTLA-4 induces 4-1BB+ regulatory T cells (Tregs) restricting ICI efficacy. These opposing roles of 4-1BB in different cellular contexts may explain the limited benefit of combinatorial immunotherapy observed in clinical trials. We identify two subsets of tumor-reactive progenitor Tex (Tpex): ICI-responsive Tpex1 and ICI-resistant Tpex2, a subset characterized by KLRB1 and IL17R. The balance of Tpex1 and Tpex2 associates with ICI response across multiple cancers, offering insights into sustaining response. This study was registered at ClinicalTrials.gov (NCT03737968).
2025-09-02 | GSE286827 | GEO
Project description:This study concurrently examined the genome, transcriptome, methylome and immune cell infiltrates in baseline tumors from advanced cutaneous melanoma patients treated with anti-PD-1 +/- anti-CTLA-4 immune checkpoint immunotherapy. Illumina MethylationEPIC BeadChip array analysis of 43 melanoma tumors was carried out as part of the study. Higher PSMB8 methylation (and therefore lower PSMB8 expression) was associated with poor response to immunotherapy. There were higher amounts of CD8+ T cells, as estimated by methylCIBERSORT, in the tumor microenvironment of good responders. Although we observed a significant correlation between PD-L1 expression and methylation of the cg197224470 CpG site, there was no significant difference between PD-L1 methylation in good and poor responders.
2021-12-09 | GSE181781 | GEO
Project description:<p>Blockade of T cell coinhibitory molecules such as CTLA-4 and PD-1, can activate T cell antitumor response. Although these immune checkpoint blockades (CTLA-4 blockade and PD-1 blockade) have shown durable response, response rate is modest. Therefore, there is a need to find stable biomarkers predictive of response to immune checkpoint blockades and to understand underlying resistance mechanisms. We collected longitudinal tumor biopsies from a cohort of metastatic melanoma patients treated with sequential immune checkpoint blockades and performed whole exome sequencing of this cohort. The comprehensive genomic characterization of tumors enabled identification of higher copy number loss burden as a resistance mechanism and clonal T cell repertoire as a predictive biomarker.</p>
| phs001425 | dbGaP
Project description:Personalized peptide vaccination (PPV) is one of the attractive immunotherapy with high immune-boosting effects. However, as with most therapeutic agents, PPV does not elicit beneficial immune and/or clinical responses in all of the treated cancer patients. To identify prognostic biomarker for the selection of patients most likely to benefit from PPV, we conducted whole genome gene expression analysis of prevaccination peripheral blood mononuclear cells (PBMCs) of 112 castration-resistant prostate cancer (CRPC) patients.
2015-02-01 | GSE53922 | GEO
Project description:<p>Immune checkpoint inhibitors are effective cancer treatments, but molecular determinants of clinical benefit are unknown. Ipilimumab and tremelimumab are antibodies against cytotoxic T-lymphocyte antigen 4 (CTLA-4). Anti-CTLA-4 treatment prolongs overall survival in patients with melanoma. CTLA-4 blockade activates T cells and enables them to destroy tumor cells.</p> <p>We obtained tumor tissue from patients with melanoma who were treated with ipilimumab or tremelimumab. Whole-exome sequencing was performed on tumors and matched blood samples. Somatic mutations and candidate neoantigens generated from these mutations were characterized. Neoantigen peptides were tested for the ability to activate lymphocytes from ipilimumab-treated patients.</p> <p>Malignant melanoma exomes from 64 patients treated with CTLA-4 blockade were characterized with the use of massively parallel sequencing. A discovery set consisted of 11 patients who derived a long-term clinical benefit and 14 patients who derived a minimal benefit or no benefit. Mutational load was associated with the degree of clinical benefit (P = 0.01) but alone was not sufficient to predict benefit. Using genomewide somatic neoepitope analysis and patient-specific HLA typing, we identified candidate tumor neoantigens for each patient. We elucidated a neo-antigen landscape that is specifically present in tumors with a strong response to CTLA-4 blockade. We validated this signature in a second set of 39 patients with melanoma who were treated with anti-CTLA-4 antibodies. Predicted neoantigens activated T cells from the patients treated with ipilimumab.</p>
| phs001041 | dbGaP