Abstract：
:Immune checkpoint inhibitors show great promise as therapy for advanced melanoma, heightening the need to determine the most effective use of these agents. Here, we report that programmed death-1(high) (PD-1(high)) tumor antigen (TA)-specific CD8(+) T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL10 receptor (IL10R) expression. Multiple subsets of peripheral blood mononucleocytes from melanoma patients produce IL10, which acts directly on IL10R(+) TA-specific CD8(+) T cells to limit their proliferation and survival. PD-1 blockade augments expression of IL10R by TA-specific CD8(+) T cells, thereby increasing their sensitivity to the immunosuppressive effects of endogenous IL10. Conversely, IL10 blockade strengthened the effects of PD-1 blockade in expanding TA-specific CD8(+) T cells and reinforcing their function. Collectively, our findings offer a rationale to block both IL10 and PD-1 to strengthen the counteraction of T-cell immunosuppression and to enhance the activity of TA-specific CD8(+) T cell in advanced melanoma patients.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Sun Z,Fourcade J,Pagliano O,Chauvin JM,Sander C,Kirkwood JM,Zarour HMdoi
10.1158/0008-5472.CAN-14-3016subject
Has Abstractpub_date
2015-04-15 00:00:00pages
1635-44issue
8eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-14-3016journal_volume
75pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:Since tumor suppressor gene DCC exhibits amino acid sequence homology to the neural cell adhesion molecule, there is a possibility that DCC might be related to tumor metastasis. In the present study, we examined 51 cases of primary esophageal carcinomas with regard to point mutations and loss of the DCC gene. We detec...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-06-01 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：:A translationally regulated, dominant-negative isoform of CCAAT/enhancer-binding protein beta is expressed in transplantable and primary mouse mammary tumors of different etiologies but is not expressed in preneoplastic mammary hyperplasias or in primary prostate, lung, lens, ovary or lymphoid tumors. The eukaryotic i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Replicative senescence limits the number of times primary cells can divide and is therefore regarded as a potential checkpoint for cancer progression. The majority of studies examining changes of gene expression upon senescence have been made with stationary senescent cells. We wanted to study the transition from norm...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-1872
更新日期：2004-01-15 00:00:00
abstract：:Combination treatment of SKCO1 human colon carcinoma cells with beta ser-interferon (IFN-beta ser) and gamma-interferon (IFN-gamma) results in a synergistic antiproliferative effect. The role of IFN-beta ser and IFN-gamma receptor modulation was investigated as a possible mechanism for this response. IFN-gamma (0.05-5...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Emerging knowledge on how the dysregulated function of signaling networks contributes to the malignant growth of squamous cell carcinoma of the head and neck (HNSCC) can now be exploited to identify novel mechanism-based anticancer treatments. In this regard, we have observed that persistent activation of the serine/t...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0921
更新日期：2005-11-01 00:00:00
abstract：:Human polynucleotide phosphorylase (hPNPase(old-35)) is a type I IFN-inducible 3',5' exoribonuclease that mediates mRNA degradation. In melanoma cells, slow and sustained overexpression of hPNPase(old-35) induces G(1) cell cycle arrest ultimately culminating in apoptosis, whereas rapid overexpression of hPNPase(old-35...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-0872
更新日期：2007-09-01 00:00:00
abstract：:To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-0444
更新日期：2008-08-01 00:00:00
abstract：:Targeted therapies can be defined as drugs developed against a specific target based on its important biological function in cancer. In contrast, nontargeted therapies are drugs identified by phenotypic screening of natural products or chemical libraries against established cancer cell lines or preclinical animal mode...
journal_title：Cancer research
pub_type： 杂志文章,评审
doi：10.1158/0008-5472.CAN-08-3836
更新日期：2009-02-15 00:00:00
abstract：:Despite the initial efficacy of androgen deprivation therapy, most patients with advanced prostate cancer eventually progress to hormone-refractory prostate cancer, for which there is no curative therapy. Previous studies from our laboratory and others have shown the antiproliferative and proapoptotic effects of 3,3'-...
journal_title：Cancer research
pub_type： 杂志文章,收录出版
doi：10.1158/0008-5472.CAN-06-2011
更新日期：2006-10-15 00:00:00
abstract：:Induction of an apoptotic cell death was studied in a mouse T-cell hybridoma. Apoptosis was induced in these cells following exposure to dexamethasone, X-radiation, 43 degrees C heat shock, A254 light, and hydrogen peroxide. In 5-Gy-exposed cells, a radiation-induced G2 phase cell cycle progression block was maximum b...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-02-15 00:00:00
abstract：:Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL-6 i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-06-15 00:00:00
abstract：:Pentraxin-3 (PTX3) is a member of the pentraxin family of innate immune regulators, which includes C-reactive protein (CRP). PTX3 has been implicated in angiogenesis, proliferation, and immune escape in cancer. In the present study, we evaluated PTX3 tissue expression and serum concentration as a biomarker to discrimi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-0369
更新日期：2014-08-15 00:00:00
abstract：:Destruction of cancer cells by cytotoxic T lymphocytes depends on immunogenic tumor peptides generated by proteasomes and presented by human leukocyte antigen (HLA) molecules. Functional differences arising from alleles of immunoproteasome subunits have not been recognized so far. We analyzed the genetic polymorphism ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-1883
更新日期：2011-12-01 00:00:00
abstract：:The purpose of the present study was to define the immunogenicity of two transplantable rat gliomas, designated F98 and D74, and to relate this to the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL). Fischer rats, immunized with irradiated F98 tumor cells and challenged with intracerebral imp...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:CBLC (CBL proto-oncogene c) belongs to the CBL protein family, which has E3 ubiquitin ligase activity toward activated receptor tyrosine kinases. CBLC is frequently upregulated in non-small cell lung cancer (NSCLC), yet very little is known about the functions of CBLC in tumorigenesis. Here we show that CBLC is an epi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-3858
更新日期：2018-09-01 00:00:00
abstract：:microRNAs (miRNA) are small noncoding RNAs that participate in diverse biological processes by suppressing target gene expression. Altered expression of miR-21 has been reported in cancer. To gain insights into its potential role in tumorigenesis, we generated miR-21 knockout colon cancer cells through gene targeting....
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-1996
更新日期：2009-10-15 00:00:00
abstract：:The mechanism by which gonadotropin-releasing hormone (GnRH) agonists and antagonists inhibit tumor cell growth and proliferation is controversial. Direct mediation of the antitumor effects through the high-affinity GnRH receptors has been questioned because of the low level of expression of receptors on the tumor cel...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-10-15 00:00:00
abstract：:Clinical photodynamic therapy consists of the systemic administration of a derivative of hematoporphyrin (Photofrin II) followed by exposure of malignant lesions to continuous visible laser irradiation. We investigated the effects of various modifications of laser light delivery on the efficacy of photodynamic therapy...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-11-15 00:00:00
abstract：:Hypoxia within solid tumors decreases therapeutic efficacy, and identification of hypoxia markers may influence the choice of therapeutic modality. Here, we used a proteomic approach to identify hypoxia-regulated proteins and validated their use as endogenous indicators of tumor hypoxia. Using two-dimensional gel elec...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-0899
更新日期：2004-10-15 00:00:00
abstract：:Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CA...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-2139
更新日期：2019-02-01 00:00:00
abstract：:Targeting of steroidogenic enzymes (e.g., abiraterone acetate targeting CYP17A1) has been developed as a novel therapeutic strategy against metastatic castration-resistant prostate cancer (CRPC). However, resistance to steroidal inhibitors inevitably develops in patients, the mechanisms of which remain largely unknown...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2341
更新日期：2018-05-01 00:00:00
abstract：:cis- and trans-diamminedichloroplatinum(II) (PDD) produced a DNA cross-linking effect in mouse leukemia L1210 cells, which was demonstrable after subtoxic treatments with the DNA alkaline elution technique. Cross-linking effects developed following treatments with concentrations as low as 1 micron for cis-PDD and 5 mi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-06-01 00:00:00
abstract：:A phenolic amine compound, 4-S-cysteaminylphenol (4-S-CAP), is a potent depigmenting agent. To develop more efficacious antimelanoma agents, we synthesized four homologues of 4-S-CAP: N-acetyl-4-S-CAP (N-Ac-4-S-CAP), alpha-methyl-4-S-CAP, 4-S-homo-CAP, and N,N'-dimethyl-4-S-CAP. We tested these five compounds in mice ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-06-15 00:00:00
abstract：:Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that is characterized by a particularly marked resistance to chemotherapy. We previously showed an association between decreased expression of BNIP3 and chemoresistance in PDAC cell lines. To further explore the molecular basis of chemoresistance in PDAC...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-0440
更新日期：2007-07-15 00:00:00
abstract：:Cellular retinoic acid-binding protein (cRABP) was detected in the cytosol of virus-induced papilloma (Shope) of rabbit skin. The Shope papilloma cRABP showed the same ligand specificity and sedimentation value (2S) as was found in other animal species. The level of cRABP in the papillomatous tissue was significantly ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-04-01 00:00:00
abstract：:Cellular immune competence was found to be impaired in previous studies of patients with malignant brain tumors. In patients with nonneural tumors, we recently found that serum levels of acute-phase proteins were related to immune status as well as to tumor extent. To determine whether the serum proteins in patients w...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-02-01 00:00:00
abstract：:The gene of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) has been implicated as an oncogene in ovarian cancer [L. Shayesteh et al., Nat. Genet., 21: 99-102, 1999]. In this study, we examined the expression of PIK3CA mRNA and its p110alpha protein product in human ovarian carcinoma and investigated it...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-07-15 00:00:00
abstract：:We have shown that cyclophosphamide (CY) can augment the development of delayed-type hypersensitivity to a primary antigen in patients with advanced cancer. In the present study, we administered CY (1000 mg/sq m) to 19 patients with advanced, metastatic cancer and monitored the compositional and functional changes in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-03-01 00:00:00
