Differentiation of tumor-infiltrating GZMK+ effector memory T cells associates with response to neoadjuvant immunotherapy in head and neck cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE296954 | GEO | 2026/06/15
REPOSITORIES: GEO
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Project description:We performed single-cell RNA/VDJ-sequencing of sorted T cells from post-treatment blood of patients with HPV-unrelated head and neck squamous cell carcinoma treated with either bintrafusp alfa alone or in combination with Tri-Ad5 vaccine. These patients are identical to the patients from which tumor-infiltrating T cells were isolated as reflected in the sample names.
2026-06-15 | GSE296867 | GEO
Project description:We performed single-cell RNA/VDJ-sequencing of sorted CD8+ T cells from the blood of patients with HPV-unrelated head and neck squamous cell carcinoma. The corresponding cells were cultured with or without aCD3/aCD28-mediated TCR stimulation. Importantly, these patients were not treated on a clinical trial and are distinct from the other patients included in this study.
2026-06-15 | GSE296771 | GEO
Project description:HPV positive head and neck cancer (HNC) are thought to have different etiology from HPV-unrelated HNC. There are indications that HPV positive HNC have better survival and that treatment options could be optimized in this set of tumours. In this study, we sought to evaluate miRNA profiles in the different groups of HNC based on cancer subsite (oral or oropharyngeal) and HPV presence (positive/negative; based on both viral DNA and RNA presence) all in comparison with normal tonsillar tissue from approximately aged subjects. From 61 enrolled patients, 22 were selected for NGS small RNA sequencing using Illumina small RNA library preparation kits and sequencing reagents on Nextseq 500 machine. Only samples with RIN >= 7 were included. manufacturers protocol was followed for library preparation. Indexing was done with indexes 1-22, and final libraries were normalizes to same amount after QBit measurement. Sequencing was done on Nextseq 500 machine and subsequent analyisis in Basespace (illumina). Raw fastq files were subsequently additionally trimmed of adapter sequences using FastQc Basespace app and differential expression evaluated with SmallRNA app. Customized plots were obtained after importing SmallRNA app calculated counts to DeSeq2 package in R and reanalysis therein.
2019-02-20 | E-MTAB-7030 | biostudies-arrayexpress
Project description:Abstract: Purpose: We evaluated whether IDO-inhibitor BMS986205 (IDOi) + PD-1 inhibitor nivolumab enhanced T-cell activity and augmented immune-mediated antitumor responses in untreated, resectable HNSCC. We employed response-adaptive surgical timing to identify responders to immunotherapy and enhance their response. Patients and Methods: Patients with HNSCC were 3:1 randomized to receive nivolumab with or without BMS986205 PO daily (NCT03854032). In the combination arm, BMS986205 was initiated 7 days prior to nivolumab. Patients were stratified by HPV status. Response-adaptive surgical timing involved response assessment by radiographic criteria 4 weeks after nivolumab in both arms. Non-responders underwent surgical resection, while responders received 4 more weeks of randomized therapy before surgery. Biomarker analysis utilized pathologic treatment response (pTR) and RNA sequencing. Results: Forty-two patients were enrolled, and the addition of IDOi to nivolumab did not result in greater rate of radiographic response (p=0.909). Treatment was well-tolerated with only 2 (5%) patients experiencing grade 3 immune-related adverse events. The addition of IDO-inhibitor augmented rates of pTR in patients with high baseline IDO RNA expression (p<0.05). Response-adaptive surgical timing demonstrated reliability in differentiating pathologic responders versus non-responders (p=0.009). A pretreatment NK cell signature, PD-L1 status, and IFN-g expression in the HPV– cohort correlated with response. HPV+ cohort found B-cell and CAF signatures predictive of response/non-response. Conclusions: Response-adaptive surgical timing enhanced treatment response. IDO-inhibitor BMS986205 augmented pTR in patients with high IDO1-expression in baseline samples, indicating a need for identifying and targeting resistant nodes to immunotherapy. HPV-status-dependent signatures predicting response to immunotherapy in HNSCC warrant further study.
2024-11-20 | GSE281729 | GEO
Project description:Acute expression of E7 oncogene from HPV-16 or HPV-18 is sufficient to overcome tumor necrosis factor-alfa (TNF) cytostatic effect on primary human keratinocytes. In the present study we investigated the molecular basis of E7-induced TNF resistance through a comparative analysis of the effect of this cytokine on the proliferation and global gene expression of organotypic cultures of normal and E7(wild type or mutant)-expressing keratinocytes.
2010-01-15 | GSE17892 | GEO
Project description:Chromatin alterations mediate mutations and gene expression changes in cancer. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) has been utilized to study genome-wide chromatin structure in human cancer cell lines, yet numerous technical challenges limit comparable analyses in primary tumors. Here we have developed a new whole-genome analytic pipeline to optimize ChIP-Seq protocols on patient-derived xenografts from human papillomavirus-related (HPV+) head and neck squamous cell carcinoma (HNSCC) samples. We further associated chromatin aberrations with gene expression changes from a larger cohort of the tumor and normal samples with RNA-Seq data. We detect differential histone enrichment associated with tumor-specific gene expression variation, sites of HPV integration in the human genome, and HPV-associated histone enrichment sites upstream of cancer driver genes, which play central roles in cancer-associated pathways. These comprehensive analyses enable unprecedented characterization of the complex network of molecular changes resulting from chromatin alterations that drive HPV-related tumorigenesis.
2018-03-20 | GSE112021 | GEO
Project description:Introduction: Human Papilloma Virus (HPV) is associated with a subset of head and neck squamous cell carcinoma (HNSCC), between 15% and 35% of HNSCC harboring HPV, almost exclusively of subtype 16. Demographic and exposure differences between HPV-positive (+) and negative (-) HNSCCs suggest that HPV(+) tumors may constitute a subclass with different biology, while clinical differences have also been observed. In this study, gene expression profiles of HPV(+) and (-) tumors were compared to further explore the biological effect of HPV in HNSCC. Methods: Thirty-six HNSCC tumors were analyzed for gene expression using Affymetrix Human 133U Plus 2.0 GeneChip and for HPV using consensus primers for HPV L1, E6 and E7 by PCR and RT-PCR. Results: Eight (22%) of 36 tumors were positive for HPV, all of the HPV 16 subtype, and the HPV positive samples also expressed viral HPV E6 mRNA determined by RT-PCR. Patients with HPV(+) HNSCCs were on average younger than those with HPV(-) tumors (mean age 50.2 vs. 58.7). Statistical analysis using Significance Analysis of Microarrays (SAM) based on HPV status as a supervising parameter resulted in a list of 91 genes that were differentially expressed with statistical significance. Results for a sub-set of these genes were verified by RT-PCR. Genes highly expressed in HPV(+) samples included cell cycle regulators (p16INK4A, p18 and CDK2) and transcription factors (TAF7L, RFC4, RPA2 and TFDP2). The microarray data were also investigated using DIGMap to map genes by chromosomal location. A large number of genes on chromosome 3q24-qter was found to be overrepresented in HPV(+) tumors. Conclusion: The gene expression profile associated with HPV reflects alterations in cell cycle and proliferation signals. Further investigation of differentially expressed genes may reveal the unique pathways in HPV(+) tumors that may explain the different natural history and biological properties of these tumors. These properties may be exploited as a target of novel therapeutic agents in HNSCC treatment. Keywords: HPV, HNSCC, head and neck cancer, human, human papilloma virus
2005-11-28 | GSE3292 | GEO
Project description:Genome wide DNA methylation profiling of HPV positive and HPV negative head and neck squamous cell cancer (HNSCC) samples. The Illumina Infinium 450k Human DNA methylation Beadchip v1.1 was used to obtain DNA methylation profiles across approximately 485577 CpGs in 4 HPV positive and 4 HPV negative HNSCC tumors
2015-03-21 | GSE67114 | GEO
Project description:Human papillomaviruses (HPVs) are associated with nearly all cervical cancers (CCs), 20-30% of head and neck cancers (HNCs), and other cancers. Because HNCs also arise in HPV-negative patients, this type of cancer provides unique opportunities to define similarities and differences of HPV-positive versus HPV-negative cancers arising in the same tissue. Here, we describe genome-wide expression profiling of 84 HNCs, CCs and site-matched normal epithelial samples in which we used laser capture microdissection to enrich samples for tumor-derived versus normal epithelial cells. This analysis revealed that HPV+HNCs and CCs differed in their patterns of gene expression yet shared many changes compared to HPV-HNCs. Some of these shared changes were predicted, but many others were not. Notably, HPV+HNCs and CCs were found to be upregulated in their expression of a distinct and larger subset of cell cycle genes than observed in HPV-HNC. Moreover, HPV+ cancers over-expressed testis-specific genes that are normally expressed only in meiotic cells. Many, though not all, of the hallmark differences between HPV+HNC and HPV-HNC were a direct consequence of HPV and in particular the viral E6 and E7 oncogenes. This included a novel association of HPV oncogenes with testes specific gene expression. These findings in primary human tumors provide novel biomarkers for early detection of HPV+ and HPV- cancers, and emphasize the potential value of targeting E6 and E7 function, alone or combined with radiation and/or traditional chemotherapy, in the treatment of HPV+ cancers. Keywords: Gene expression ptofiles of primary cancers
2007-05-15 | GSE6791 | GEO
Project description:Tumour-infiltrating lymphocytes are a major predictor for overall survival and response to immunotherapy for several malignancies. However, while tumour-infiltrating CD8 T cells have been extensively studied, little is known about the role of the humoral immune system within the tumour microenvironment (TME). Here we show that plasma cells are present in the TME and actively secrete human papillomavirus (HPV)-specific IgG antibodies in HPV-positive head and neck squamous cell carcinoma patients. Compared to circulating memory B cells, plasma cells in the TME were enriched for HPV-reactivity with little bystander recruitment of influenza-specific cells. HPV-specific plasma cells in the TME correlated with the antibody titres in peripheral blood and produced antibodies with a high degree of somatic hypermutation directed against HPV E2, E6 and E7 antigens. A striking proportion of HPV-specific antibodies produced in situ were directed against E2, which might thus be a promising target for immunotherapies in HPV-associated cancers. Overall, we show that antigen-specific activated and germinal centre B cells as well as plasma cells can be found in the TME, with plasma cells producing antibodies specific for tumour-associated antigens in situ. These findings provide a better understanding of humoral immune responses in human cancer and suggest that tumour-infiltrating B cells could be harnessed for the development of novel therapeutic agents.
2020-07-20 | GSE149327 | GEO