当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

Abstract：

:Infiltration of human cancers by T cells is generally interpreted as a sign of immune recognition, and there is a growing effort to reactivate dysfunctional T cells at such tumor sites1. However, these efforts only have value if the intratumoral T cell receptor (TCR) repertoire of such cells is intrinsically tumor reactive, and this has not been established in an unbiased manner for most human cancers. To address this issue, we analyzed the intrinsic tumor reactivity of the intratumoral TCR repertoire of CD8+ T cells in ovarian and colorectal cancer-two tumor types for which T cell infiltrates form a positive prognostic marker2,3. Data obtained demonstrate that a capacity to recognize autologous tumor is limited to approximately 10% of intratumoral CD8+ T cells. Furthermore, in two of four patient samples tested, no tumor-reactive TCRs were identified, despite infiltration of their tumors by T cells. These data indicate that the intrinsic capacity of intratumoral T cells to recognize adjacent tumor tissue can be rare and variable, and suggest that clinical efforts to reactivate intratumoral T cells will benefit from approaches that simultaneously increase the quality of the intratumoral TCR repertoire.

journal_name

Nat Med

journal_title

Nature medicine

authors

Scheper W,Kelderman S,Fanchi LF,Linnemann C,Bendle G,de Rooij MAJ,Hirt C,Mezzadra R,Slagter M,Dijkstra K,Kluin RJC,Snaebjornsson P,Milne K,Nelson BH,Zijlmans H,Kenter G,Voest EE,Haanen JBAG,Schumacher TN

doi

10.1038/s41591-018-0266-5

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

89-94

issue

1

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-018-0266-5

journal_volume

25

pub_type

杂志文章

相关文献

NATURE MEDICINE文献大全
  • Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

    abstract：:Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4055

    authors： Camarda R,Zhou AY,Kohnz RA,Balakrishnan S,Mahieu C,Anderton B,Eyob H,Kajimura S,Tward A,Krings G,Nomura DK,Goga A

    更新日期：2016-04-01 00:00:00

  • The TAM receptor Mertk protects against neuroinvasive viral infection by maintaining blood-brain barrier integrity.

    abstract：:The TAM receptors Tyro3, Axl and Mertk are receptor tyrosine kinases that dampen host innate immune responses following engagement with their ligands Gas6 and Protein S, which recognize phosphatidylserine on apoptotic cells. In a form of apoptotic mimicry, many enveloped viruses display phosphatidylserine on the outer...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3974

    authors： Miner JJ,Daniels BP,Shrestha B,Proenca-Modena JL,Lew ED,Lazear HM,Gorman MJ,Lemke G,Klein RS,Diamond MS

    更新日期：2015-12-01 00:00:00

  • Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression.

    abstract：:Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-bo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0497-447

    authors： Bargou RC,Jürchott K,Wagener C,Bergmann S,Metzner S,Bommert K,Mapara MY,Winzer KJ,Dietel M,Dörken B,Royer HD

    更新日期：1997-04-01 00:00:00

  • Modulation of T-cell-mediated immunity in tumor and graft-versus-host disease models through the LIGHT co-stimulatory pathway.

    abstract：:LIGHT was recently described as a member of the tumor necrosis factor (TNF) 'superfamily'. We have isolated a mouse homolog of human LIGHT and investigated its immunoregulatory functions in vitro and in vivo. LIGHT has potent, CD28-independent co-stimulatory activity leading to T-cell growth and secretion of gamma int...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/73136

    authors： Tamada K,Shimozaki K,Chapoval AI,Zhu G,Sica G,Flies D,Boone T,Hsu H,Fu YX,Nagata S,Ni J,Chen L

    更新日期：2000-03-01 00:00:00

  • Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposure.

    abstract：:Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8+ lymphocytes had greater anti-HIV-1 activity than did CD8+ lymphocy...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0496-412

    authors： Paxton WA,Martin SR,Tse D,O'Brien TR,Skurnick J,VanDevanter NL,Padian N,Braun JF,Kotler DP,Wolinsky SM,Koup RA

    更新日期：1996-04-01 00:00:00

  • Author Correction: China's response to a novel coronavirus stands in stark contrast to the 2002 SARS outbreak response.

    abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title：Nature medicine

    pub_type： 杂志文章,已发布勘误

    doi：10.1038/s41591-020-0816-5

    authors： Nkengasong J

    更新日期：2020-03-01 00:00:00

  • Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis.

    abstract：:Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemic...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1026

    authors： Harman FS,Nicol CJ,Marin HE,Ward JM,Gonzalez FJ,Peters JM

    更新日期：2004-05-01 00:00:00

  • A novel viral mechanism for dysregulation of beta-catenin in Kaposi's sarcoma-associated herpesvirus latency.

    abstract：:The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is expressed in all KSHV-associated tumors, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We found that beta-catenin is overexpressed in both PEL cells and KS tissue. Introduction of anti-LANA small inte...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm829

    authors： Fujimuro M,Wu FY,ApRhys C,Kajumbula H,Young DB,Hayward GS,Hayward SD

    更新日期：2003-03-01 00:00:00

  • Detection of tumor angiogenesis in vivo by alphaVbeta3-targeted magnetic resonance imaging.

    abstract：:Angiogenesis, the formation of new blood vessels, is a requirement for malignant tumor growth and metastasis. In the absence of angiogenesis, local tumor expansion is suppressed at a few millimeters and cells lack routes for distant hematogenous spread. Clinical studies have demonstrated that the degree of angiogenesi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0598-623

    authors： Sipkins DA,Cheresh DA,Kazemi MR,Nevin LM,Bednarski MD,Li KC

    更新日期：1998-05-01 00:00:00

  • Skeletal remodeling in health and disease.

    abstract：:The use of genetically manipulated mouse models, gene and protein discovery and the cataloguing of genetic mutations have each allowed us to obtain new insights into skeletal morphogenesis and remodeling. These techniques have made it possible to identify molecules that are obligatory for specific cellular functions, ...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm1593

    authors： Zaidi M

    更新日期：2007-07-01 00:00:00

  • Angiopoietin-related growth factor antagonizes obesity and insulin resistance.

    abstract：:Angiopoietin-related growth factor (AGF), a member of the angiopoietin-like protein (Angptl) family, is secreted predominantly from the liver into the systemic circulation. Here, we show that most (>80%) of the AGF-deficient mice die at about embryonic day 13, whereas the surviving AGF-deficient mice develop marked ob...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1214

    authors： Oike Y,Akao M,Yasunaga K,Yamauchi T,Morisada T,Ito Y,Urano T,Kimura Y,Kubota Y,Maekawa H,Miyamoto T,Miyata K,Matsumoto S,Sakai J,Nakagata N,Takeya M,Koseki H,Ogawa Y,Kadowaki T,Suda T

    更新日期：2005-04-01 00:00:00

  • Autism risk in offspring can be assessed through quantification of male sperm mosaicism.

    abstract：:De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessin...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0711-0

    authors： Breuss MW,Antaki D,George RD,Kleiber M,James KN,Ball LL,Hong O,Mitra I,Yang X,Wirth SA,Gu J,Garcia CAB,Gujral M,Brandler WM,Musaev D,Nguyen A,McEvoy-Venneri J,Knox R,Sticca E,Botello MCC,Uribe Fenner J,Pérez MC

    更新日期：2020-01-01 00:00:00

  • The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux.

    abstract：:Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/87912

    authors： Synold TW,Dussault I,Forman BM

    更新日期：2001-05-01 00:00:00

  • gammadelta T cells provide a breath of fresh air for asthma research.

    abstract：:gammadelta T cells downregulate airways responsiveness to allergen challenge, possibly by controlling the 'repair' response of the airway epithelium to alphabeta T cell-mediated damage (pages 1150-1156). ...

    journal_title：Nature medicine

    pub_type： 评论,新闻

    doi：10.1038/13447

    authors： Holt PG,Sly PD

    更新日期：1999-10-01 00:00:00

  • Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial.

    abstract：:The impact of single-agent antibodies against programmed death-ligand 1 (PD-L1) as maintenance therapy is unknown in patients with metastatic breast cancer. The SAFIR02-BREAST IMMUNO substudy included patients with human epidermal growth factor receptor type 2 (Her2)-negative metastatic breast cancer whose disease did...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-01189-2

    authors： Bachelot T,Filleron T,Bieche I,Arnedos M,Campone M,Dalenc F,Coussy F,Sablin MP,Debled M,Lefeuvre-Plesse C,Goncalves A,Reynier MM,Jacot W,You B,Barthelemy P,Verret B,Isambert N,Tchiknavorian X,Levy C,Thery JC,L'Har

    更新日期：2021-01-18 00:00:00

  • Cancer's true breakthroughs.

    abstract：:A new regulatory pathway established last year allows drugs with dramatic early clinical promise to be expedited to the market quicker than ever before. To date, most of these 'breakthrough' designations have gone to cancer agents, raising the prospect of faster access to the latest lifesaving therapies for the estima...

    journal_title：Nature medicine

    pub_type： 新闻

    doi：10.1038/nm.3245

    authors： Dolgin E

    更新日期：2013-06-01 00:00:00

  • Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection.

    abstract：:Viral replication and microbial translocation from the gut to the blood during HIV infection lead to hyperimmune activation, which contributes to the decline in CD4+ T cell numbers during HIV infection. Programmed death-1 (PD-1) and interleukin-10 (IL-10) are both upregulated during HIV infection. Blocking interaction...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2106

    authors： Said EA,Dupuy FP,Trautmann L,Zhang Y,Shi Y,El-Far M,Hill BJ,Noto A,Ancuta P,Peretz Y,Fonseca SG,Van Grevenynghe J,Boulassel MR,Bruneau J,Shoukry NH,Routy JP,Douek DC,Haddad EK,Sekaly RP

    更新日期：2010-04-01 00:00:00

  • Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants.

    abstract：:Defects in major histocompatibility complex (MHC) class I-restricted antigen presentation are frequently observed in human cancers and result in escape of tumors from cytotoxic T lymphocyte (CTL) immune surveillance in mice. Here, we show the existence of a unique category of CTLs that can prevent this escape. The CTL...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1381

    authors： van Hall T,Wolpert EZ,van Veelen P,Laban S,van der Veer M,Roseboom M,Bres S,Grufman P,de Ru A,Meiring H,de Jong A,Franken K,Teixeira A,Valentijn R,Drijfhout JW,Koning F,Camps M,Ossendorp F,Kärre K,Ljunggren HG,Mel

    更新日期：2006-04-01 00:00:00

  • A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice.

    abstract：:The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes under...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4311

    authors： Bilkei-Gorzo A,Albayram O,Draffehn A,Michel K,Piyanova A,Oppenheimer H,Dvir-Ginzberg M,Rácz I,Ulas T,Imbeault S,Bab I,Schultze JL,Zimmer A

    更新日期：2017-06-01 00:00:00

  • A newly discovered human pneumovirus isolated from young children with respiratory tract disease.

    abstract：:From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/89098

    authors： van den Hoogen BG,de Jong JC,Groen J,Kuiken T,de Groot R,Fouchier RA,Osterhaus AD

    更新日期：2001-06-01 00:00:00

  • Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts.

    abstract：:It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene1. The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches2-5. For patients in whom WES is uninformative...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0457-8

    authors： Frésard L,Smail C,Ferraro NM,Teran NA,Li X,Smith KS,Bonner D,Kernohan KD,Marwaha S,Zappala Z,Balliu B,Davis JR,Liu B,Prybol CJ,Kohler JN,Zastrow DB,Reuter CM,Fisk DG,Grove ME,Davidson JM,Hartley T,Joshi R,Stro

    更新日期：2019-06-01 00:00:00

  • Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1.

    abstract：:How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Stro...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1297-1389

    authors： Gauduin MC,Parren PW,Weir R,Barbas CF,Burton DR,Koup RA

    更新日期：1997-12-01 00:00:00

  • Imaging of angiogenesis: from microscope to clinic.

    abstract：:Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and an...

    journal_title：Nature medicine

    pub_type： 杂志文章,评审

    doi：10.1038/nm0603-713

    authors： McDonald DM,Choyke PL

    更新日期：2003-06-01 00:00:00

  • Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress.

    abstract：:Activation of the zinc-finger transcription factor early growth response (Egr)-1, initially linked to developmental processes, is shown here to function as a master switch activated by ischemia to trigger expression of pivotal regulators of inflammation, coagulation and vascular hyperpermeability. Chemokine, adhesion ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/82168

    authors： Yan SF,Fujita T,Lu J,Okada K,Shan Zou Y,Mackman N,Pinsky DJ,Stern DM

    更新日期：2000-12-01 00:00:00

  • Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery.

    abstract：:Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a ...

    journal_title：Nature medicine

    pub_type： 临床试验,杂志文章

    doi：10.1038/nm0402-415

    authors： Mikszta JA,Alarcon JB,Brittingham JM,Sutter DE,Pettis RJ,Harvey NG

    更新日期：2002-04-01 00:00:00

  • Studying clonal dynamics in response to cancer therapy using high-complexity barcoding.

    abstract：:Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3841

    authors： Bhang HE,Ruddy DA,Krishnamurthy Radhakrishna V,Caushi JX,Zhao R,Hims MM,Singh AP,Kao I,Rakiec D,Shaw P,Balak M,Raza A,Ackley E,Keen N,Schlabach MR,Palmer M,Leary RJ,Chiang DY,Sellers WR,Michor F,Cooke VG,Korn JM

    更新日期：2015-05-01 00:00:00

  • Effect of an intravitreal antisense oligonucleotide on vision in Leber congenital amaurosis due to a photoreceptor cilium defect.

    abstract：:Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) wit...

    journal_title：Nature medicine

    pub_type： 临床试验,杂志文章

    doi：10.1038/s41591-018-0295-0

    authors： Cideciyan AV,Jacobson SG,Drack AV,Ho AC,Charng J,Garafalo AV,Roman AJ,Sumaroka A,Han IC,Hochstedler MD,Pfeifer WL,Sohn EH,Taiel M,Schwartz MR,Biasutto P,Wit W,Cheetham ME,Adamson P,Rodman DM,Platenburg G,Tome MD,

    更新日期：2019-02-01 00:00:00

  • In situ genetic analysis of cellular chimerism.

    abstract：:Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish betw...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.1862

    authors： Wu D,Vu Q,Nguyen A,Stone JR,Stubbs H,Kuhlmann G,Sholl LM,Iafrate AJ

    更新日期：2009-02-01 00:00:00

  • A molecularly engineered split reporter for imaging protein-protein interactions with positron emission tomography.

    abstract：:Improved techniques to noninvasively image protein-protein interactions (PPIs) are essential. We molecularly engineered a positron emission tomography (PET)-based split reporter (herpes simplex virus type 1 thymidine kinase), cleaved between Thr265 and Ala266, and used this in a protein-fragment complementation assay ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2185

    authors： Massoud TF,Paulmurugan R,Gambhir SS

    更新日期：2010-08-01 00:00:00

  • Role of NMDA receptor-dependent activation of SREBP1 in excitotoxic and ischemic neuronal injuries.

    abstract：:Excitotoxic neuronal damage caused by overactivation of N-methyl-D-aspartate glutamate receptors (NMDARs) is thought to be a principal cause of neuronal loss after stroke and brain trauma. Here we report that activation of sterol regulatory element binding protein-1 (SREBP-1) transcription factor in affected neurons i...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2064

    authors： Taghibiglou C,Martin HG,Lai TW,Cho T,Prasad S,Kojic L,Lu J,Liu Y,Lo E,Zhang S,Wu JZ,Li YP,Wen YH,Imm JH,Cynader MS,Wang YT

    更新日期：2009-12-01 00:00:00