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Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed

ABSTRACT: Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed

PROVIDER: PRJNA765694 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16028500.fastq.gz	Fastqsanger.gz
	SRR16028501.fastq.gz	Fastqsanger.gz
	SRR16028502.fastq.gz	Fastqsanger.gz
	SRR16028503.fastq.gz	Fastqsanger.gz
	SRR16028496.fastq.gz	Fastqsanger.gz

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Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed.

Project description:Advances in high-throughput sequencing have revolutionized the manner with which we can study T cell responses. We describe a woman who received a human papillomavirus (HPV) therapeutic vaccine called PepCan, and experienced complete resolution of her cervical high-grade squamous intraepithelial lesion. By performing bulk T cell receptor (TCR) β deep sequencing of peripheral blood mononuclear cells before and after 4 vaccinations, 70 putatively vaccine-specific clonotypes were identified for being significantly increased using a beta-binomial model. In order to verify the vaccine-specificity of these clonotypes, T cells with specificity to a region, HPV 16 E6 91-115, previously identified to be vaccine-induced using an interferon-γ enzyme-linked immunospot assay, were sorted and analyzed using single-cell RNA-seq and TCR sequencing. HPV specificity in 60 of the 70 clonotypes identified to be vaccine-specific was demonstrated. TCR β bulk sequencing of the cervical liquid-based cytology samples and cervical formalin-fixed paraffin-embedded samples before and after 4 vaccinations demonstrated the presence of these HPV-specific T cells in the cervix. Combining traditional and cutting-edge immunomonitoring techniques enabled us to demonstrate expansion of HPV-antigen specific T cells not only in the periphery but also in the cervix. Such an approach should be useful as a novel approach to assess vaccine-specific responses in various anatomical areas.

| S-EPMC8515132 | biostudies-literature

Expansion of Human Papillomavirus-Specific T Cells in Periphery and Cervix in a Therapeutic Vaccine Recipient Whose Cervical High-Grade Squamous Intraepithelial Lesion Regressed

Project description:Single-cell TCR/transcriptome analysis for a peripheral blood lymphocytes (PBL) specimen was perform on a 10X Chromium instrument using a single-cell VDJ kit

2021-09-25 | GSE184703 | GEO

Dysregulation of miRNA in adenocarcinoma of the uterine cervix

Project description:We identified an altered miRNA expression in adenocarcinoma of the uterine cervix compared with normal cervix and futhermore analyzed their association with clinicopthologic characteristics.

2014-03-01 | GSE55478 | GEO

Hormonal regulation of cervix transcript expression in the menstrual cycle

Project description:The aim of this study was to identify hormonally regulated genes and their related biological pathways in the rhesus macaque cervix during the menstrual cycle. The cervix is the gateway for gamete passage, which is driven by hormonal regulation with progesterone (P) suppressing the passage of gametes. Contraceptives that are progesterone based change the cervix. Progestogen only contraception is reported to act by suppressing ovulation and/or altering cervical mucus secretion. In order to further investigate novel contraceptive targets and their pathways, a microarray was used to discover genes in the cervix that are suppressed under varying lengths of exposure to progesterone throughout an artificial menstrual cycle.

2018-02-13 | GSE110476 | GEO

Epigenome analysis of smear cells from the uterine cervix consisting of 24 normals and 24 cervical intraepithelial neoplasias (all HPV+)

Project description:The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs in smear cells from the uterine cervix (liquid based cytology samples), obtained from 48 women. All women tested positive for the human papilloma virus (HPV+). Of the 48 samples, 24 were cytologically normal while the other 24 exhibited morphological transformation (cervical intraepithelial neoplasia of grade 2 or higher - CIN2+).

2013-03-30 | GSE37020 | GEO

Oxysterol 25-hydroxycholesterol activation of ferritinophagy inhibits the development of squamous intraepithelial lesion of cervix in HPV-positive patients.

Project description:Squamous intraepithelial lesion of cervix (SIL) in human papillomavirus (HPV)-positive patient often undergoes a silent and long-course development, and most of them with high-grade transit to cervical squamous cell carcinoma (CSCC). The oxysterol 25-hydroxycholesterol (25-HC) is associated with HPV inhibition, autophagy and cholesterol synthesis, however, its function in this long process of SIL development remain unclear. In this study, we demonstrate that 25-HC generation is inhibited through HSIL-to-CSCC transition. The 25-HC activates ferritinophagy in the early stage of SIL, promoting the vulnerability of HSILs to ferroptosis. Therefore, maintaining 25-HC level is crucial for suppressing HSIL progression and holds promise for developing novel clinical therapies for CSCC.

| S-EPMC10933481 | biostudies-literature

Clinicopathological Characteristics of Pleomorphic High-Grade Squamous Intraepithelial Lesion of the Uterine Cervix: A Single-Institutional Series of 31 Cases.

Project description:We investigated the clinicopathological characteristics of 31 cases of pleomorphic high-grade squamous intraepithelial lesions (PHSIL) of the uterine cervix. We reviewed electronic medical records and all available slides to collect clinical and pathological information. PHSILs were histologically characterized by significant nuclear enlargement, marked pleomorphism, hyperchromasia, increased mitotic activity, and frequent atypical mitoses. In the majority of cases (24/31; 77.4%), this striking nuclear atypia involved both the surface epithelium and the endocervical glands. In the remaining seven cases, pleomorphic cells were observed in the surface epithelium only. PHSILs involving both the surface epithelium and glands showed higher mitotic counts and Ki-67 labelling indices than the surface-only PHSILs. Invasive squamous cell carcinoma was present in only one case (3.2%), and none developed recurrent disease. Our observations of striking nuclear atypia in cases of HSIL did not indicate increased aggressiveness. Further investigations are required for confirmation of our data in larger cohorts.

| S-EPMC7459519 | biostudies-literature

Epigenome analysis of smear cells from the uterine cervix consisting of 24 normals and 24 cervical intraepithelial neoplasias (all HPV+)

2013-03-30 | E-GEOD-37020 | biostudies-arrayexpress

Macrophage gene expression associated with remodeling of the prepartum rat cervix: Microarray and pathway analyses

Project description:As the critical gatekeeper for birth, prepartum remodeling of the cervix is associated with increased resident macrophages (Mφ), proinflammatory processes, and extracellular matrix degradation. This study tested the hypothesis that expression of genes unique to Mφs characterizes the prepartum from unremodeled nonpregnant cervix. Perfused cervix from prepartum day 21 postbreeding (D21) or nonpregnant (NP) rats, with or without Mφs, had RNA extracted and whole genome microarray analysis performed. By subtractive analyses, expression of 194 and 120 genes related to Mφs in the cervix from D21 rats were increased and decreased, respectively. In both D21 and NP groups, 158 and 57 Mφ genes were also more or less up- or down-regulated, respectively.

2015-01-27 | GSE65265 | GEO

Stability of miRNA in FFPE tumour samples exhibiting degraded mRNA [Cervix samples miRNA]

Project description:Background: As degradation of formalin-fixed paraffin-embedded (FFPE) samples limits ability to expression profile, we explored factors predicting success for FFPE profiling and investigated an approach overcoming this limitation. Methods: Bladder (n=141, stored 3-8 years) and cervix (n=160, stored 8-23 years) carcinoma FFPE samples were hybridised to Affymetrix Exon1.0ST arrays. Percent detection above background (%DABG) measured technical success. Biological signal was assessed by distinguishing cervix squamous cell carcinoma (SCC) and adenocarcinoma (AC) using a gene signature. Precursor mir-205 was measured by Exon array and mature miR-205 by qRT-PCR. Eight-old and -young cervix samples were compared using Affymetrix miRNA 2.0 arrays. For comparison, the 'cervix_tumour_cs1_113' (previsously submitted GSM677307) was included and re-analyzed with the samples from the current study (total 161 Cervix samples). Results: RNA quality controls (e.g. RNA integrity number) failed to predict profiling success, but sample age correlated with %DABG in bladder (R2=-0.30, p<0.01) and cervix (R2=-0.69, p<0.01). Biological signal was lost in older samples and neither a signature nor precursor mir-205 separated samples by histology. miR-205 qRT-PCR discriminated SCC from AC, validated by miRNA profiling (26-fold higher in SCC; p=1.10x10-5). Median miRNA probeset expression of eight-old and eight-young cervix samples correlated well (R2=0.95) overcoming the age-related bias of mRNA probesets, suggesting miR-205 stability generalises across microRNA. Conclusions: microRNA profiling overcomes the limitation of degraded FFPE samples

2012-07-04 | GSE39015 | GEO

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