Abstract:
:Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10). Public single-cell gene expression data from 17 HPV-negative HNSCC were separately reanalyzed. APOBEC3-associated TCW motif mutations but not total single nucleotide variant burden were significantly associated with inflammation. This association was restricted to HPV-negative HNSCC samples. An APOBEC-enriched, HPV-negative subgroup was identified, that showed higher T-cell inflammation and immune checkpoint expression, as well as expression of APOBEC3 genes. Mutations in immune-evasion pathways were also enriched in these tumors. Analysis of single-cell sequencing data identified expression of APOBEC3B and 3C genes in malignant cells. We identified an APOBEC-enriched subgroup of HPV-negative HNSCC with a distinct immunogenic phenotype, potentially mediating response to immunotherapy.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Messerschmidt C,Obermayer B,Klinghammer K,Ochsenreither S,Treue D,Stenzinger A,Glimm H,Fröhling S,Kindler T,Brandts CH,Schulze-Osthoff K,Weichert W,Tinhofer I,Klauschen F,Keilholz U,Beule D,Rieke DTdoi
10.1002/ijc.33123subject
Has Abstractpub_date
2020-10-15 00:00:00pages
2293-2302issue
8eissn
0020-7136issn
1097-0215journal_volume
147pub_type
杂志文章abstract::A challenging task of the immune system is to fight cancer cells. However, a variety of human cancers educate immune cells to become tumor supportive. This is exemplified for tumor-associated macrophages (TAMs), which are polarized towards an anti-inflammatory and cancer promoting phenotype. Mechanistic explanations, ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24594
更新日期:2009-11-01 00:00:00
abstract::Heat shock protein (HSP) gp96/grp94 contains a signal peptide at the amino terminus and a -KDEL sequence at the carboxy terminus and is a major component of the lumen of the mammalian endoplasmic reticulum (ER). We show, by a number of immunolocalization methods using light and electron microscopy, that a significant ...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960822)69:4<340::AID-IJC
更新日期:1996-08-22 00:00:00
abstract::Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit proliferation and angiogenesis in colorectal cancer. We examined a possible involvement of store-operated calcium (SOC) entry in human colon carcinoma cells (HRT-18), which require calcium for proliferation. Acetyl-salicylic-acid (ASA), mefenamic acid (MEF) and su...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1280
更新日期:2001-06-15 00:00:00
abstract::Subcellular distribution of hexokinase (HK) isoenzymes in 22 human breast cancers (21 primary cancers and 1 axillary metastatic growth) and 7 non-pathological human mammary gland tissue samples was studied with starch gel electrophoresis on isolated cell fractions obtained by differential centrifugation. Fractions use...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910340111
更新日期:1984-07-15 00:00:00
abstract::Phenotypic and functional characteristics of tumor-infiltrating lymphocytes (TIL) obtained from human primary and metastatic liver tumors were studied. Lymphocytes isolated from 18 tumors and autologous (A) peripheral blood (6 cases) were phenotyped by 2-color flow cytometry and cloned in a limiting dilution system, w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910460521
更新日期:1990-11-15 00:00:00
abstract::We previously reported identifying SOX6 as a glioma antigen by serological screening using a testis cDNA library. Its preferential expression and frequent IgG responses in glioma patients indicate that SOX6 may be a useful target for immunotherapy. To examine whether cytotoxic T-lymphocyte (CTL) responses specific for...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23366
更新日期:2008-05-15 00:00:00
abstract::Reverse-transcriptase polymerase chain reaction has been used to analyze the expression of 2 latent genes (EBNA-1 and LMP-1) and one replicative gene (BZLF-1) of Epstein-Barr virus in mononuclear cells from bone marrow and peripheral blood of healthy donors. EBV-gene transcription was detected in 8 out of 15 bone-marr...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19970304)70:5<524::aid-ijc
更新日期:1997-03-04 00:00:00
abstract::G-protein-coupled receptor (GPCR)-stimulated androgen-independent activation of androgen receptor (AR) contributes to acquisition of a hormone-refractory phenotype by prostate cancer. We previously reported that regulator of G-protein signaling (RGS) 2, an inhibitor of GPCRs, inhibits androgen-independent AR activatio...
journal_title:International journal of cancer
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doi:10.1002/ijc.26138
更新日期:2012-04-01 00:00:00
abstract::Transcription factor c-Jun serves for cellular proliferation, survival, differentiation and transformation and is recognized as an important factor in cancer development, including hepatocellular carcinoma (HCC). The purpose of present study is to determine the involvement of c-Jun in matrix metalloproteinase-1 (MMP-1...
journal_title:International journal of cancer
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doi:10.1002/ijc.20095
更新日期:2004-05-10 00:00:00
abstract::Adenoviral oncolysis is a promising new modality for treatment of cancer based on selective viral replication in tumor cells. However, tumor cell killing by adenoviral oncolysis needs to be improved to achieve therapeutic benefit in the clinic. Towards this end, the activation of anti-tumor immunity by adenoviral onco...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23074
更新日期:2008-01-01 00:00:00
abstract::The importance of tumor associated neutrophils (TANs) in cancer development is in the meantime well established. Numerous of clinical data document the adverse prognostic effects of neutrophil infiltration in solid tumors. However, certain tumor therapies need functional neutrophils to be effective, suggesting altered...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29945
更新日期:2016-04-15 00:00:00
abstract::Hereditary non-polyposis colorectal cancer (HNPCC) is known to be associated with several extracolonic cancers, e.g., cancers of the endometrium, stomach, urinary tract, small bowel and ovary. An association between HNPCC and brain tumours has also been reported, although previous risk analysis did not reveal an exces...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(SICI)1097-0215(19960208)65:4<422::AID-IJC
更新日期:1996-02-08 00:00:00
abstract::Cervical cancer and many other anogenital and oropharyngeal carcinomas are strongly associated with high-risk human papillomavirus (HPV) persistent infections. HPV E7 oncoprotein is the major viral transforming factor, emerging as a natural candidate for immunotherapy, since it is constitutively expressed in HPV-induc...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.26294
更新日期:2012-04-15 00:00:00
abstract::Oncogene-transformed fibroblasts which expressed IL-1, spontaneously or after activation with conditioned medium (CM) and lipopolysaccharide (LPS), regressed in the syngeneic host. Since regression was significantly influenced by the immune competence of the host (see companion report), we speculated that regression w...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910500321
更新日期:1992-02-01 00:00:00
abstract::Cell lines derived from 13 different human colon adenocarcinomas were examined for production of fibronectin by ELISA and for cell-surface expression of fibronectin by indirect immunofluorescence. Two squamous epithelial cell lines obtained from tumors of the upper aerodigestive tract were used as controls. None of th...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910470319
更新日期:1991-02-01 00:00:00
abstract::Data from immunocytochemical assessment of estrogen receptor (ER) regulation in MCF-7 cells under estrogenic and anti-estrogenic stimulation were compared with those obtained by enzyme immunoassay (Abbott ER-EIA). Similar trends were observed, although ER level variations were less marked when assessed immunocytochemi...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19981209)78:6<760::aid-ijc
更新日期:1998-12-09 00:00:00
abstract::A reanalysis of the Women's Health Initiative (WHI) randomized clinical trial found a significant interaction between supplementation with vitamin D/calcium and estrogen therapy and the risk of colorectal cancer risk, with reduced risks from supplementation limited to the placebo arms of the estrogen trials. To explor...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24903
更新日期:2010-04-15 00:00:00
abstract::EPLIN is frequently downregulated or lost in various cancers. The purpose of this study was to evaluate the importance of EPLIN in prostate cancer progression, with particular focus on the mechanistic implications to elucidate EPLIN's tumor suppressive function in cancer. EPLIN expression was evaluated in prostate can...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.31786
更新日期:2018-11-15 00:00:00
abstract::Folate-mediated one-carbon metabolism plays critical roles in DNA synthesis, repair and DNA methylation. The impact of single nucleotide polymorphisms (SNPs) in folate-metabolizing enzymes has been investigated in risk of breast cancer among European or Asian populations, but not among women of African ancestry. We co...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29434
更新日期:2015-08-01 00:00:00
abstract::Transducer of ErbB-2 (TOB) is a member of the TOB/Btg gene family. A role for TOB in the suppression of human tumorigenesis has been proposed, based on the observations that TOB-knockout mice spontaneously form tumors and TOB expression is lost in human lung and thyroid cancers. However, the role of TOB in human breas...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.24490
更新日期:2009-10-15 00:00:00
abstract::Our aim was to determine the long-term outcome and the possible role of neoadjuvant (preoperative) radiation therapy for breast cancers unsuitable for primary conservative surgery. From 1977 to 1992, 75 unifocal non-inflammatory and non-metastatic T2 and T3 breast cancers were treated in our department. All these pati...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1024
更新日期:2001-08-20 00:00:00
abstract::Activated T cells expressing endogenous or transduced TCRs are two cell types currently used in clinical adoptive T-cell therapy. The ability of these cells to recognize their antigen, expand and traffic to the tumor site are the initial steps necessary for successful therapy. In this study, we used in vivo biolumines...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.29401
更新日期:2015-07-15 00:00:00
abstract::IL-21 is a member of the IL-2 cytokine family, produced by CD4+ T cells. We previously showed that immunotherapy (IT) with IL-21-transduced neuroblastoma cells (Neuro2a/IL-21) cured 33% of syngeneic mice bearing systemic NB. Here, we studied whether the removal of Treg cells could potentiate the therapeutic efficacy o...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.25140
更新日期:2010-09-01 00:00:00
abstract::The effects on cell survival in tissue culture of Adriamycin, of various Adriamycin derivatives and of the parent compound, daunomycin, have been studied. Adriamycin and three of its C-14 derivatives show similar toxicities towards cells chronically exposed in culture. Acute (30 min) exposures are significantly less t...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910190209
更新日期:1977-02-15 00:00:00
abstract::Oncogenic mutations of the ras gene leading to constitutive activation of downstream effectors have been detected in a large spectrum of human cancers (pancreas, thyroid, colon and NSCLC). Membrane anchorage of Ras required for functional activity in signal transduction is facilitated by post-translational modificatio...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/(sici)1097-0215(19991008)83:2<283::aid-ijc
更新日期:1999-10-08 00:00:00
abstract::Incidence rates of Wilms' tumor (WT) markedly differ in East Asian and Caucasian children. In the present study, we examined WT1 deletions/mutations and loss of heterozygosity (LOH) on 11p and 11q in a large number of WTs and compared our findings with those from 4 series of Caucasian WTs. Incidence rates of the subtl...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.1475
更新日期:2001-11-01 00:00:00
abstract::Renal-cell carcinomas (RCC) are clinically, histologically and cytogenetically very heterogeneous. The present histological WHO classification shows no clear correlation between histologic subtypes and specific chromosomal abnormalities. In 1986, a new classification was proposed by Thoenes and Störkel based on the ce...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910550210
更新日期:1993-09-09 00:00:00
abstract::To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean e...
journal_title:International journal of cancer
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doi:10.1002/(sici)1097-0215(19990420)84:2<169::aid-ijc
更新日期:1999-04-20 00:00:00
abstract::Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Little is known about its molecular pathogenesis and the relevance of DNA methylation for disease initiation and progression. Nevertheless, promoter methylation of some genes has been implicated as potential marker for HCC. Thirty-four HCC, 34...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.23433
更新日期:2008-06-15 00:00:00
abstract::Malignant tumors are generally characterized by extensive local tissue invasion and destruction of ECM which may be due to increased constitutive expression and activity of secreted proteases. Moreover, a large number of diverse protease activities may be constitutively over-expressed in a simultaneous or co-ordinated...
journal_title:International journal of cancer
pub_type: 杂志文章
doi:10.1002/ijc.2910480413
更新日期:1991-06-19 00:00:00