Abstract:
:Immunosuppression may contribute to the progression of cancer. In this study we assessed the structural and functional status of T cells from tumor specimens obtained from patients with early stage non-small cell lung cancer and late-stage ovarian cancer. Although some groups have described structural alterations in the TCR in patients with other malignancies, we did not observe decreased expression of the CD3zeta subunit in the tumor-associated T cells. However, increased percentages of CD4(+)CD25(+) T cells were observed in the non-small cell lung cancer tumor-infiltrating lymphocytes and ovarian cancer tumor-associated lymphocytes. Furthermore, these CD4(+)CD25(+) T cells were found to secrete transforming growth factor-beta, consistent with the phenotype of regulatory T cells. Despite a generalized expression of lymphocyte activation markers in the tumor-associated T-cell populations, the CD8(+) T cells expressed low levels of CD25. To determine whether expression of CD25 could be restored on the CD8 cells, tumor-associated T cells were stimulated with anti-CD3 and anti-CD28 monoclonal antibodies. After stimulation, nearly all of the CD8 T cells expressed CD25. Furthermore, despite the low levels of interleukin 2, IFN-gamma, and tumor necrosis factor-alpha secretion by the tumor-associated and peripheral blood T cells at baseline, stimulation with anti-CD3 and anti-CD28 monoclonal antibodies significantly increased the fraction of cells producing these cytokines. Thus, tumor-associated T cells from patients with early and late-stage epithelial tumors contain increased proportions of CD4(+)CD25(+) T cells that secrete the immunosuppressive cytokine transforming growth factor-beta. Furthermore, our results are consistent with previous reports showing impaired expression of CD25 on CD8(+) T cells in cancer patients. Finally, increased lymphocyte costimulation provided by triggering the CD28 receptor is able to increase CD25 expression and cytokine secretion in tumor-associated T cells. These observations provide evidence for the contribution of regulatory T cells to immune dysfunction in cancer patients.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Woo EY,Chu CS,Goletz TJ,Schlienger K,Yeh H,Coukos G,Rubin SC,Kaiser LR,June CHsubject
Has Abstractpub_date
2001-06-15 00:00:00pages
4766-72issue
12eissn
0008-5472issn
1538-7445journal_volume
61pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Animal models, particularly mouse models, play a central role in the study of the etiology, prevention, and treatment of human prostate cancer. While tissue culture models are extremely useful in understanding the biology of prostate cancer, they cannot recapitulate the complex cellular interactions within the tumor m...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-4213
更新日期:2013-05-01 00:00:00
abstract::FET cells, derived from an early-stage colon carcinoma, are nontumorigenic in athymic mice. Stable transfection of a dominant-negative transforming growth factor beta (TGFbeta) type II receptor (DNRII) into FET cells that express autocrine TGFbeta shows loss of TGFbeta signaling and increased tumorigenicity in vivo in...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5348
更新日期:2008-05-01 00:00:00
abstract::Intercellular communication was compared in early passage cultures of human mammary epithelial cells (HMEC) from normal and malignant breast tissues and immortalized nontumorigenic human breast cell lines (184A1 and 184B5). A clonogenic assay for the cell-mediated transfer of toxic metabolites of 6-thioguanine (TG) be...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Cells that overexpress high-mobility group A1 (HMGA1) proteins exhibit deficient nucleotide excision repair (NER) after exposure to DNA-damaging agents, a condition ameliorated by artificially lowering intracellular levels of these nonhistone proteins. One possible mechanism for this NER inhibition is down-regulation ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1689
更新日期:2007-07-01 00:00:00
abstract::Eph tyrosine kinases instruct cell for a repulsive behavior, regulating cell shape, adhesion, and motility. Beside its role during embryogenesis, neurogenesis, and angiogenesis, EphA2 kinase is frequently up-regulated in tumor cells of different histotypes, including prostate, breast, colon, and lung carcinoma, as wel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1845
更新日期:2009-03-01 00:00:00
abstract::Tumor cell interaction with endothelial cells is a crucial step leading to organ-selective metastasis. Adhesion of murine B16 amelanotic melanoma cells (B16a) to murine microvascular endothelial cells (CD3) was enhanced, in a dose- and time-dependent manner, by pretreating CD3 cells with 12(S)-hydroperoxyeicosatetraen...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-02-15 00:00:00
abstract::Intrahepatic cholangiocarcinoma (IHCC) is a primary cancer of the liver with an increasing incidence and poor prognosis. Preclinical studies of the etiology and treatment of this disease are hampered by the relatively small number of available IHCC cell lines or genetically faithful animal models. Here we report the d...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-11-3596
更新日期:2012-03-15 00:00:00
abstract::Little is known about the genetic changes underlying invasive tumor growth in bladder cancer. Because alterations that are linked to invasive tumor growth may be detectable in minimally invasive (stage pT1) but not in noninvasive (stage pTa) tumors, we searched for genetic differences between 28 pTa and 28 papillary p...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-15 00:00:00
abstract::Although immunotherapies of tumors have demonstrated promise for altering the progression of malignancies, immunotherapies have been limited by an immunosuppressive tumor microenvironment (TME) that prevents infiltrating immune cells from performing their anticancer functions. Prominent among immunosuppressive cells a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1414
更新日期:2020-11-17 00:00:00
abstract::Cells deficient in DNA polymerase beta (beta-pol) are impaired in base excision repair (BER) and hypersensitive to various DNA damaging agents, including methylating mutagens. Hypersensitivity of beta-pol-deficient cells to methylating agents is because of induction of apoptosis (Ochs et al., Cancer Res., 59: 1544-155...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::A common form of multidrug resistance in human cancer results from expression of the MDR1 gene which encodes a plasma membrane energy-dependent multidrug efflux pump. We have engineered transgenic mice which express this multidrug transporter in their bone marrow cells and demonstrated that peripheral WBC of these ani...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-10-01 00:00:00
abstract::Nerve growth factor-like substance(s) were identified in both conditioned media of a human prostatic tumor epithelial cell line (TSU-pr1) and a human prostatic stromal cell line (HPS) by Western blot analysis and bioassay of neurite outgrowth of PC12 cells. Nerve growth factor-beta (NGF) immunofluorescence was also lo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-06-15 00:00:00
abstract::Latent prostate tumors are commonly found with similar frequency in many countries and ethnic groups. In contrast, aggressive prostate cancer (PC) is significantly less prevalent among Asian men, where the intake of soy products is very high. High consumption of foods containing soy results in high plasma, urine, and ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-09-15 00:00:00
abstract::Transfection of C3H/10T1/2 cells with either a c-myc or an activated c-Ha-ras gene decreased the cellular dependence for serum-derived factors to proliferate in monolayer. The c-myc-transfected cells did, however, require a high plasma concentration for significant growth, while the ras transfectants grew extremely we...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous los...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::The effects of the antitumorigenic drug estramustine on tumor cell membrane penetration (invasion) were investigated in vitro by utilizing a synthetic basement membrane system (a modified Boyden chamber). Tumor cells were plated on a "partition barrier," consisting of a porous filter (8-micron pores) which was coated ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-11-15 00:00:00
abstract::It has been postulated that the intestinal anaerobes play a role in the etiology of large bowel cancer. This study was designed to characterize and compare the fecal anaerobes of patients with large bowel cancer, patients with nonhereditary large bowel polyps, and healthy control subjects. Although some distributional...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-12-01 00:00:00
abstract::Cancer procoagulant (CP) is a Mr 68,000 cysteine proteinase that initiates blood coagulation and is expressed by a variety of malignant cells but not by normally differentiated cells. Polyclonal immunoglobulin G and monoclonal immunoglobulin M antibodies were developed to purified CP and used to develop an enzyme-link...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-10-01 00:00:00
abstract::We have screened 57 cases of primary, nonfunctional, pituitary adenomas for loss of heterozygosity of markers on chromosome 9p. Using a panel of 11 microsatellite markers, we found hemizygous deletion with at least one of the markers in 18 tumors (31.5%). The frequency of loss was similar in both noninvasive (8 of 26;...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-01 00:00:00
abstract::The histone demethylase KDM4B is frequently overexpressed in various cancer types, and previous studies have indicated that the primary oncogenic function of KDM4B is its ability to demethylate H3K9me3 in different tumors, resulting in altered gene expression and genome instability. A genome-wide analysis to evaluate ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-1310
更新日期:2019-01-01 00:00:00
abstract::To define genetic determinants of tumor cell resistance to the cytotoxic action of tumor necrosis factor alpha (TNF), we have applied cDNA microarrays to a human breast carcinoma TNF-sensitive MCF7 cell line and its established TNF-resistant clone. Of a total of 5760 samples of cDNA examined, 3.6% were found to be dif...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1735
更新日期:2004-01-15 00:00:00
abstract::Tyrosine phosphorylation (pTyr) plays a pivotal role in signal transduction and is commonly dysregulated in cancer. As a result, profiling tumor pTyr levels may reveal therapeutic insights critical to combating disease. Existing discovery and targeted mass spectrometry-based methods used to monitor pTyr networks invol...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-3804
更新日期:2021-01-28 00:00:00
abstract::Advances in cancer research and personalized medicine will require significant new bridging infrastructures, including more robust biorepositories that link human tissue to clinical phenotypes and outcomes. In order to meet that challenge, four cancer centers formed the Text Information Extraction System (TIES) Cancer...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-15-1973
更新日期:2015-12-15 00:00:00
abstract::Elevated levels of TGFβ are a negative prognostic indicator for patients diagnosed with pancreatic cancer; as a result, the TGFβ pathway is an attractive target for therapy. However, clinical application of pharmacologic inhibition of TGFβ remains challenging because TGFβ has tumor suppressor functions in many epithel...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-1807
更新日期:2014-09-15 00:00:00
abstract::We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::We used comparative genomic hybridization to study malignant fibrous histiocytomas (MFHs) from 19 patients to detect changes in the copy number of DNA sequences, along entire chromosomes. Together with losses and gains in various chromosomal regions, distinct high-level amplifications were found at six loci (4q12-21, ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::1-Nitropyrene (1-NP) originating from such sources as diesel exhaust emissions and coal combustion fly ash has been detected in the environment. 1-NP, in addition to being both a bacterial and mammalian mutagen, is carcinogenic in rats. The purpose of this study was to quantitate 1-NP metabolism and macromolecular cov...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::Insulin-like growth factor (IGF) I has important growth regulatory functions in normal growth and development. IGF-I is also a mitogen for a number of cancer cell lines; however, its autocrine effect has not been well established. In this study, the expression of IGF-I, its receptor, and its major serum-binding protei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::Cell differentiation within stem cell lineages can check proliferative potential, but nodal pathways that can limit tumor growth are obscure. Here, we report that lung cancer cell populations generate phenotypic and oncogenic plasticity via a switch between differentiation programs controlled by SOX2 and SOX9, thus al...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3178
更新日期:2016-12-01 00:00:00
abstract::Fumitremorgin C (FTC) is a potent and specific chemosensitizing agent in cell lines selected for resistance to mitoxantrone that do not overexpress P-glycoprotein or multidrug resistance protein. The gene encoding a novel transporter, the breast cancer resistance protein (BCRP), was recently found to be overexpressed ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00