Immuno-genomic landscape of osteosarcoma
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ABSTRACT:
PROVIDER: EGAS00001004197 | EGA |
REPOSITORIES: EGA
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Project description:Osteosarcoma is an orphan disease affecting children and young adults that has seen little to no progress in survival outcomes for >30 years. Despite having heavily rearranged genomes, to date, clinical trials with immunotherapy have shown no benefit for patients with osteosarcoma. In this study, we conducted the first multi-platform immune profiling (whole genome, transcriptome, T-cell receptor sequencing, immunohistochemistry and reverse phase protein array) on every available pediatric and adult osteosarcoma patients from our institution (N = 48) with the goal of describing immune features that may contribute to immunotherapy resistance.
| EGAS00001003887 | EGA
Project description:Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20-30%. T cell checkpoint blockade immunotherapies have revolutionized cancer treatment in the last decade, but their impact remains limited in osteosarcoma. In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterization of a unique sample set comprising multiple osteosarcoma samples from seven patients, collected throughout the progression of the disease. We performed RNA-sequencing and imaging mass cytometry analysis on those samples to reveal the immunological landscape during osteosarcoma progression. Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anti-cancer immunity were enriched in metastatic lesions as compared to primary tumors. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly MAGEA-related antigens, in osteosarcoma metastases. Their overexpression in metastatic lesions was confirmed at protein level and positive expression of MAGEA3 in primary tumors showed a significant association with metastasis free survival. Importantly, we demonstrated the presentation of MAGE-derived peptides in three osteosarcoma cell lines. These findings indicate a concurrent augmentation of cytotoxic anti-tumor immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation warrants the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.
2024-02-07 | GSE237033 | GEO
Project description:Leveraging the conserved cancer genomes across mammals has the potential to transform driver gene discovery in orphan cancers. Here, we combine cross-species genomics with validation across human-dog-mouse systems to uncover a new osteosarcoma driver genes. This widely applicable cross-species approach serves as a platform to expedite search of cancer drivers in rare human malignancies offering new targets for cancer therapy.
2021-03-08 | GSE111637 | GEO
Project description:Osteosarcoma have heavily rearranged genomes and moderate tumor mutation burden, which suggests that the patients may express neoantigens that could be targeted by immune cells. To characterize the immunogenomic landscape of this disease, we performed genome, transcriptome, immune and proteomic profiling of 48 patients comprised largely of relapsed and metastatic cases from both pediatric and adult patients.
| EGAS00001003247 | EGA
Project description:<p>This is a genome-wide association study (GWAS) of osteosarcoma, the most common primary bone malignancy. Osteosarcoma typically occurs in adolescents and young adults. It occurs at increased frequency in several inherited cancer predisposition syndromes but the genetic contribution to sporadic osteosarcoma is largely unexplored. The objective of this study was to identify genetic risk factors for osteosarcoma by conducting a genome-wide association study.</p> <p>We developed collaborations with multiple institutions in order to attain the necessary sample size required to discover novel loci in the genome associated with osteosarcoma using the GWAS approach. Genomic DNA (either blood or buccal in source) derived from osteosarcoma cases was obtained from each participating institution or research group.</p> <p>De-identified blood or buccal cell DNA samples from osteosarcoma cases were derived from existing biobanks at the collaborative institutions. Control subjects were derived from existing NCI cohorts and matched by gender and ethnicity.</p>
| phs000734 | dbGaP
Project description:We utilized murine osteosarcoma cell lines F420 and K7M2. F420 was originally derived from a female C57BL/6 mouse transgenic for a mutant p53 under control of a bone-selective promoter (PMID: 25579177). K7M2 was derived from a spontaneous metastatic lesion in a female Balb/C background (PMID: 16837208). F420 osteosarcoma tumors were established by subcutaneously injecting 5 x 10^6 osteosarcoma cells into the flanks of 6-week-old C57BL/6 mice (Envigo, Frederick, MD). K7M2 tumors were established by transplanting small pieces of sectioned tumor (~2mm3) into the flanks of 6-week-old Balb/C mice (Envigo). We found K7M2 to be more immunogenic than F420 as it demonstrated higher immune cell infiltrates, higher expression of immune-related genes, and slower growth in syngeneic versus nude models.
2021-06-29 | GSE166282 | GEO
Project description:Paget's associated osteosarcoma
| PRJNA343233 | ENA
Project description:In order to identify the targets of miR-193a-5p in osteosarcoma U2OS cell line, we used a lentivirus-mediated expression system to overexpressing miR-193a precusor, miR-193a-5p target sequence and non-target sequence, respectively, in osteosarcoma cell line U2OS. A tandem mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-193a-5p-regulated proteins. order to identify the targets of miR-193a-5p, we used a lentivirus-mediated expression system to overexpressing miR-193a precusor, miR-193a-5p target sequence and non-target sequence, respectively, in osteosarcoma cell line U2OS. A tandem mass tag (TMT)-based quantitative proteomic strategy was employed to identify the global profile of miR-193a-5p-regulated proteins.
2021-09-08 | PXD013987 | Pride
Project description:Limited clinical activity has been seen in osteosarcoma (OS) patients treated with immune checkpoint inhibitors (ICI). To gain insights into the immunogenic potential of these tumors, we conducted whole genome, RNA, and T-cell receptor sequencing, immunohistochemistry and reverse phase protein array profiling (RPPA) on OS specimens from 48 pediatric and adult patients with primary, relapsed, and metastatic OS. Median immune infiltrate level was lower than in other tumor types where ICI are effective, with concomitant low T-cell receptor clonalities. Neoantigen expression in OS was lacking and significantly associated with high levels of nonsense-mediated decay (NMD). Samples with low immune infiltrate had higher number of deleted genes while those with high immune infiltrate expressed higher levels of adaptive resistance pathways. PARP2 expression levels were significantly negatively associated with the immune infiltrate. Together, these data reveal multiple immunosuppressive features of OS and suggest immunotherapeutic opportunities in OS patients.
| S-EPMC7035358 | biostudies-literature
Project description:expression analysis from a genetically engineered mouse model of osteosarcoma determine the expression profile of mouse osteosarcoma Keywords: disease state analysis
2008-06-15 | GSE9460 | GEO