Differential tumor immune microenvironment coupled with tumor progression or tumor eradication in HPV-antigen expressing squamous cell carcinoma (SCC) models.
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ABSTRACT:
PROVIDER: PRJNA1131003 | ENA |
REPOSITORIES: ENA
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Project description:Human papilloma virus (HPV) is an etiological factor of head and neck squamous cell carcinoma (HNSCC). To investigate the role of HPV antigen in anti-tumor immunity, we established mouse models by expressing HPV16 E6 and E7 in a SCC tumor cell line. We obtained two HPV antigen-expressing clones (C-225 and C-100) transplantable into C57BL/6 recipients. We found that C-225 elicited complete eradication in C57BL/6 mice (eradicated), whereas C-100 grew progressively (growing). We examined immune tumor microenvironment (TME) using flow cytometry and found that eradicated or growing tumors exhibited differential immune profiles that may influence the outcome of anti-tumor immunity. Surprisingly, the percentage of CD8 and CD4 tumor-infiltrating lymphocytes (TILs) was much higher in growing (C-100) than eradicated (C-225) tumor. However, the TILs upregulated PD-1 and LAG-3 more potently and exhibited impaired effector functions in growing tumor compared to their counterparts in eradicated tumor. C-225 TME is highly enriched with myeloid cells, especially polymorphonuclear (PMN) myeloid-derived suppressor cells (MDSC), whereas the percentage of M-MDSC and tumor-associated macrophages (TAMs) was much higher in C-100 TME, especially M2-TAMs (CD206+). The complete eradication of C-225 depended on CD8 T cells and elicited anti-tumor memory responses upon secondary tumor challenge. We employed DNA sequencing to identify differences in the T cell receptor of peripheral blood lymphocytes pre- and post-secondary tumor challenge. Lastly, C-225 and C-100 tumor lines harbored different somatic mutations. Overall, we uncovered differential immune TME that may underlie the divergent outcomes of anti-tumor immunity by establishing two SCC tumor lines, both of which express HPV16 E6 and E7 antigens. Our experimental models may provide a platform for pinpointing tumor-intrinsic versus host-intrinsic differences in orchestrating an immunosuppressive TME in HNSCCs and for identifying new targets that render tumor cells vulnerable to immune attack.
2024-07-09 | GSE271371 | GEO
Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines. The Affymetrix Human Genome U133 Plus 2.0 Array platform was used to assess genome-wide expression differences between the HPV(+) and HPV(-) cell lines utilizing the RMA normalization package available for R. Cell lines analyzed: UM-SCC-4, UM-SCC-47, UM-SCC-74A, and CaSki.
2010-12-01 | E-GEOD-24089 | biostudies-arrayexpress
Project description:Oncogenic human papillomaviruses (HPVs) are associated with nearly all carcinomas of the uterine cervix and have also become an increasingly important factor in the etiology of a subset of oropharyngeal tumors. HPV-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. We analyzed the genome-wide expression patterns in two HPV(+) and two HPV(-) squamous cell carcinoma (SCC) cell lines.
2010-12-01 | GSE24089 | GEO
Project description:Differential tumor immune microenvironment coupled with tumor progression or tumor eradication in HPV- antigen expressing squamous cell carcinoma (SCC) models
| PRJNA1124061 | ENA
Project description:To identify HPV interaction region, two cell lines (UPCI-SCC-090, UM-SCC-104) were subjected to 4C-seq analysis.
2023-01-06 | GSE211280 | GEO
Project description:Human papillomavirus (HPV)-associated head and neck cancers (HNSCCs) have a distinct risk profile and appreciate a prognostic advantage compared to HPV-negative HNSCC. Promoter hypermethylation has been widely recognized as an important mechanism in the progression of HNSCC, but the extent to which this mechanism is consistent between HPV(+) and HPV(-) tumors is unknown. To assess the genome-wide methylation changes in HPV(+) and HPV(-) tumors, we analyzed DNA methylation and expression patterns in two HPV(+) and two HPV(-) cell lines. HPV(+) tumors have overall higher DNA methylation in genic and LINE1 regions than HPV(-) tumors, and polycomb repressive complex 2 (PRC2) targets tend to be much more highly methylated in HPV(+) cells. Bisulphite-converted DNA from 4 squamous cell carcinoma (SCC) cell lines were hybridized to the Illumina Infinium 27k Human Methylation Beadchip.
2010-12-01 | E-GEOD-24087 | biostudies-arrayexpress
Project description:Although adenocarcinoma of the cervix (ADC) exhibits a more malignant phenotype and poorer prognosis than squamous cell carcinoma (SCC), they are treated identically. This clinical dilemma calls for deeper investigation into differences between SCC and ADC. We studied 3 human papillomavirus (HPV)-positive SCC, 3 HPV-associated (HPVA) and 2 non-HPV-associated (NHPVA) ADC samples with single-cell RNA and T cell receptor sequencing plus 3D organoid verification. Notably, we revealed the malignant origin of epithelial cells characterized by stemness and poor differentiation and the potential mechanism of HPVA and NHPVA oncogenesis, deciphering differences between SCC and ADC. Additionally, we discovered the key role of tip cells in sprouting angiogenesis, the protumoral effects of cancer-associated fibroblasts and the functional dysregulation of T lymphocytes. We highlighted tumor microenvironment differences between different histologic subtypes through cellular interaction analysis. Importantly, we discovered novel precise treatment strategies specifically for HPV-positive SCC, HPVA and NHPVA-ADC, providing tremendous clinical value.
2023-12-01 | GSE197461 | GEO
Project description:To investigate the regulatory mechanisms and targets of the activation of NF-kB and inflammatory pathways, we treated HPV(-) head and neck cancer line UM-SCC 46 cells with TNFα and LTβ at different time points, and compared the gene expression by microarray. TNFα uniquely induced 172 genes, LTβ specifically induced 202 genes, while 155 genes were induced by both ligands. Total RNA samples were isolated from UM-SCC 46 cells after TNFα or LTβ treatment at different time points, and the gene expression were compared with untreated cell controls.
2019-02-22 | GSE126904 | GEO
Project description:To investigate the regulatory mechanisms and targets of the activation of NF-kappaB and inflammatory pathways, we treated HPV(-) head and neck cancer line UM-SCC 46 cells with TNFα and LTβ at different time points, and compared the gene expression by microarray. TNFα uniquely induced 172 genes, LTβ specifically induced 202 genes, while 155 genes were induced by both ligands. Total RNA samples were isolated from UM-SCC 46 cells after TNFα or LTβ treatment at different time points, and the gene expression were compared with untreated cell controls.
2019-02-22 | GSE126903 | GEO
Project description:Despite its prevalence, the molecular basis of squamous cell carcinoma (SCC) remains poorly understood. We recently identified the developmental transcription factor Grhl3 as a potent tumor suppressor of SCC, and demonstrated that targeting of Grhl3 by a miR-21-dependent proto-oncogenic network underpins SCC in humans. Reduced levels of GRHL3 and its target gene PTEN are evident in human skin, and head and neck SCC, associated with increased expression of miR-21, which targets both tumor suppressors. Our data defines the miR-21-GRHL3-PTEN-axis as a critical tumor suppressor pathway in SCC.
2013-01-18 | GSE32868 | GEO