当前位置： SCI文献检索 > NATURE MEDICINE期刊下所有文献 > Developing neoantigen-targeted T cell-based treatments for solid tumors.

Developing neoantigen-targeted T cell-based treatments for solid tumors.

Abstract：

:Stimulating an immune response against cancer through adoptive transfer of tumor-targeting lymphocytes has shown great promise in hematological malignancies, but clinical efficacy against many common solid epithelial cancers remains low. Targeting 'neoantigens'-the somatic mutations expressed only by tumor cells-might enable tumor destruction without causing undue damage to vital healthy tissues. Major challenges to targeting neoantigens with T cells include heterogeneity and variability in antigen processing and presentation of targets by tumors, and an incomplete understanding of which T cell qualities are essential for clinically effective therapies. Finally, the prospect of targeting somatic tumor mutations to promote T cell destruction of cancer must contend with the biology that not all tumor-expressed 'neoepitopes' actually generate neoantigens that can be functionally recognized and provoke an effective immune response. In this Review, we discuss the promise, progress and challenges for improving neoantigen-targeted T cell-based immunotherapies for cancer.

journal_name

Nat Med

journal_title

Nature medicine

authors

Yamamoto TN,Kishton RJ,Restifo NP

doi

10.1038/s41591-019-0596-y

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

1488-1499

issue

10

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-019-0596-y

journal_volume

25

pub_type

杂志文章,评审

相关文献

NATURE MEDICINE文献大全
  • Inositol- and folate-resistant neural tube defects in mice lacking the epithelial-specific factor Grhl-3.

    abstract：:The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation st...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm961

    authors： Ting SB,Wilanowski T,Auden A,Hall M,Voss AK,Thomas T,Parekh V,Cunningham JM,Jane SM

    更新日期：2003-12-01 00:00:00

  • Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein.

    abstract：:The glycosylation of the circulating immunoglobulin-gamma (IgG) antibody molecules changes in rheumatoid arthritis. The extent of the changes correlates with the disease severity and reverses in remission. We demonstrate here that the alteration in glycosylation associated with rheumatoid arthritis can create a new mo...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0395-237

    authors： Malhotra R,Wormald MR,Rudd PM,Fischer PB,Dwek RA,Sim RB

    更新日期：1995-03-01 00:00:00

  • Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing.

    abstract：:With the goal of modeling human disease of the large intestine, we sought to develop an effective protocol for deriving colonic organoids (COs) from differentiated human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Extensive gene and immunohistochemical profiling confirmed that the derived C...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4355

    authors： Crespo M,Vilar E,Tsai SY,Chang K,Amin S,Srinivasan T,Zhang T,Pipalia NH,Chen HJ,Witherspoon M,Gordillo M,Xiang JZ,Maxfield FR,Lipkin S,Evans T,Chen S

    更新日期：2017-07-01 00:00:00

  • TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.

    abstract：:Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evoke...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1758

    authors： Yamamoto S,Shimizu S,Kiyonaka S,Takahashi N,Wajima T,Hara Y,Negoro T,Hiroi T,Kiuchi Y,Okada T,Kaneko S,Lange I,Fleig A,Penner R,Nishi M,Takeshima H,Mori Y

    更新日期：2008-07-01 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

  • A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis.

    abstract：:Checkpoint inhibitors produce durable responses in numerous metastatic cancers, but immune-related adverse events (irAEs) complicate and limit their benefit. IrAEs can affect organ systems idiosyncratically; presentations range from mild and self-limited to fulminant and fatal. The molecular mechanisms underlying irAE...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0523-2

    authors： Johnson DB,McDonnell WJ,Gonzalez-Ericsson PI,Al-Rohil RN,Mobley BC,Salem JE,Wang DY,Sanchez V,Wang Y,Chastain CA,Barker K,Liang Y,Warren S,Beechem JM,Menzies AM,Tio M,Long GV,Cohen JV,Guidon AC,O'Hare M,Chandra S

    更新日期：2019-08-01 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

  • A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1.

    abstract：:Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1675

    authors： Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

    更新日期：2007-12-01 00:00:00

  • The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress.

    abstract：:Autophagy, an evolutionarily conserved process for the bulk degradation of cytoplasmic components, serves as a cell survival mechanism in starving cells. Although altered autophagy has been observed in various heart diseases, including cardiac hypertrophy and heart failure, it remains unclear whether autophagy plays a...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1574

    authors： Nakai A,Yamaguchi O,Takeda T,Higuchi Y,Hikoso S,Taniike M,Omiya S,Mizote I,Matsumura Y,Asahi M,Nishida K,Hori M,Mizushima N,Otsu K

    更新日期：2007-05-01 00:00:00

  • Elucidation of novel 13-series resolvins that increase with atorvastatin and clear infections.

    abstract：:Endogenous mechanisms leading to host protection and resolution of infections without immunosuppression are of wide interest. Here we elucidate the structures of four new host-protective molecules produced in neutrophil-endothelial cocultures and present in human and mouse tissues after sterile inflammation or infecti...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3911

    authors： Dalli J,Chiang N,Serhan CN

    更新日期：2015-09-01 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

  • Prostate cancer-associated SPOP mutations confer resistance to BET inhibitors through stabilization of BRD4.

    abstract：:The bromodomain and extraterminal (BET) family of proteins comprises four members-BRD2, BRD3, BRD4 and the testis-specific isoform BRDT-that largely function as transcriptional coactivators and play critical roles in various cellular processes, including the cell cycle, apoptosis, migration and invasion. BET proteins ...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.4378

    authors： Dai X,Gan W,Li X,Wang S,Zhang W,Huang L,Liu S,Zhong Q,Guo J,Zhang J,Chen T,Shimizu K,Beca F,Blattner M,Vasudevan D,Buckley DL,Qi J,Buser L,Liu P,Inuzuka H,Beck AH,Wang L,Wild PJ,Garraway LA,Rubin MA,Barb

    更新日期：2017-09-01 00:00:00

  • High plasma HDL concentrations associated with enhanced atherosclerosis in transgenic mice overexpressing lecithin-cholesteryl acyltransferase.

    abstract：:A subset of patients with high plasma HDL concentrations have enhanced rather than reduced atherosclerosis. We have developed a new transgenic mouse model overexpressing human lecithin-cholesteryl acyltransferase (LCAT) that has elevated HDL and increased diet-induced atherosclerosis. LCAT transgenic mouse HDLs are ab...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0797-744

    authors： Bérard AM,Föger B,Remaley A,Shamburek R,Vaisman BL,Talley G,Paigen B,Hoyt RF Jr,Marcovina S,Brewer HB Jr,Santamarina-Fojo S

    更新日期：1997-07-01 00:00:00

  • Local immune monitoring.

    abstract：: ...

    journal_title：Nature medicine

    pub_type： 评论,杂志文章

    doi：10.1038/s41591-018-0332-z

    authors： Stower H

    更新日期：2019-01-01 00:00:00

  • Racioethnic diversity in the dynamics of the vaginal microbiome during pregnancy.

    abstract：:The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-019-0465-8

    authors： Serrano MG,Parikh HI,Brooks JP,Edwards DJ,Arodz TJ,Edupuganti L,Huang B,Girerd PH,Bokhari YA,Bradley SP,Brooks JL,Dickinson MR,Drake JI,Duckworth RA 3rd,Fong SS,Glascock AL,Jean S,Jimenez NR,Khoury J,Koparde VN,La

    更新日期：2019-06-01 00:00:00

  • Genomic signatures to guide the use of chemotherapeutics.

    abstract：:Using in vitro drug sensitivity data coupled with Affymetrix microarray data, we developed gene expression signatures that predict sensitivity to individual chemotherapeutic drugs. Each signature was validated with response data from an independent set of cell line studies. We further show that many of these signature...

    journal_title：Nature medicine

    pub_type： 杂志文章,收录出版

    doi：10.1038/nm1491

    authors： Potti A,Dressman HK,Bild A,Riedel RF,Chan G,Sayer R,Cragun J,Cottrill H,Kelley MJ,Petersen R,Harpole D,Marks J,Berchuck A,Ginsburg GS,Febbo P,Lancaster J,Nevins JR

    更新日期：2006-11-01 00:00:00

  • DNA repair processes are critical mediators of p53-dependent tumor suppression.

    abstract：:It has long been assumed that p53 suppresses tumor development through induction of apoptosis, possibly with contributions by cell cycle arrest and cell senescence1,2. However, combined deficiency in these three processes does not result in spontaneous tumor formation as observed upon loss of p53, suggesting the exist...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-018-0043-5

    authors： Janic A,Valente LJ,Wakefield MJ,Di Stefano L,Milla L,Wilcox S,Yang H,Tai L,Vandenberg CJ,Kueh AJ,Mizutani S,Brennan MS,Schenk RL,Lindqvist LM,Papenfuss AT,O'Connor L,Strasser A,Herold MJ

    更新日期：2018-07-01 00:00:00

  • HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders.

    abstract：:Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3932

    authors： Janes H,Herbeck JT,Tovanabutra S,Thomas R,Frahm N,Duerr A,Hural J,Corey L,Self SG,Buchbinder SP,McElrath MJ,O'Connell RJ,Paris RM,Rerks-Ngarm S,Nitayaphan S,Pitisuttihum P,Kaewkungwal J,Robb ML,Michael NL,Mullins JI

    更新日期：2015-10-01 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

  • Polygenic architecture informs potential vulnerability to drug-induced liver injury.

    abstract：:Drug-induced liver injury (DILI) is a leading cause of termination in drug development programs and removal of drugs from the market; this is partially due to the inability to identify patients who are at risk1. In this study, we developed a polygenic risk score (PRS) for DILI by aggregating effects of numerous genome...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/s41591-020-1023-0

    authors： Koido M,Kawakami E,Fukumura J,Noguchi Y,Ohori M,Nio Y,Nicoletti P,Aithal GP,Daly AK,Watkins PB,Anayama H,Dragan Y,Shinozawa T,Takebe T

    更新日期：2020-10-01 00:00:00

  • Notch3 signaling promotes the development of pulmonary arterial hypertension.

    abstract：:Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2021

    authors： Li X,Zhang X,Leathers R,Makino A,Huang C,Parsa P,Macias J,Yuan JX,Jamieson SW,Thistlethwaite PA

    更新日期：2009-11-01 00:00:00

  • Re-engineered CD40 receptor enables potent pharmacological activation of dendritic-cell cancer vaccines in vivo.

    abstract：:Modest clinical outcomes of dendritic-cell (DC) vaccine trials call for the refinement of DC vaccine design. Although many potential antigens have been identified, development of methods to enhance antigen presentation by DCs has lagged. We have engineered a potent, drug-inducible CD40 (iCD40) receptor that permits te...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1183

    authors： Hanks BA,Jiang J,Singh RA,Song W,Barry M,Huls MH,Slawin KM,Spencer DM

    更新日期：2005-02-01 00:00:00

  • Production of atypical measles in rhesus macaques: evidence for disease mediated by immune complex formation and eosinophils in the presence of fusion-inhibiting antibody.

    abstract：:The severe disease atypical measles occurred when individuals immunized with a poorly protective inactivated vaccine contracted measles, and was postulated to be due to a lack of fusion-inhibiting antibodies. Here, rhesus macaques immunized with formalin-inactivated measles vaccine developed transient neutralizing and...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/9473

    authors： Polack FP,Auwaerter PG,Lee SH,Nousari HC,Valsamakis A,Leiferman KM,Diwan A,Adams RJ,Griffin DE

    更新日期：1999-06-01 00:00:00

  • Preoperative ipilimumab plus nivolumab in locoregionally advanced urothelial cancer: the NABUCCO trial.

    abstract：:Preoperative immunotherapy with anti-PD1 plus anti-CTLA4 antibodies has shown remarkable pathological responses in melanoma1 and colorectal cancer2. In NABUCCO (ClinicalTrials.gov: NCT03387761 ), a single-arm feasibility trial, 24 patients with stage III urothelial cancer (UC) received two doses of ipilimumab and two ...

    journal_title：Nature medicine

    pub_type： 杂志文章,多中心研究

    doi：10.1038/s41591-020-1085-z

    authors： van Dijk N,Gil-Jimenez A,Silina K,Hendricksen K,Smit LA,de Feijter JM,van Montfoort ML,van Rooijen C,Peters D,Broeks A,van der Poel HG,Bruining A,Lubeck Y,Sikorska K,Boellaard TN,Kvistborg P,Vis DJ,Hooijberg E,Schumac

    更新日期：2020-12-01 00:00:00

  • Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma.

    abstract：:Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing h...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm903

    authors： Mattiasson G,Shamloo M,Gido G,Mathi K,Tomasevic G,Yi S,Warden CH,Castilho RF,Melcher T,Gonzalez-Zulueta M,Nikolich K,Wieloch T

    更新日期：2003-08-01 00:00:00

  • GABAergic excitation after febrile seizures induces ectopic granule cells and adult epilepsy.

    abstract：:Temporal lobe epilepsy (TLE) is accompanied by an abnormal location of granule cells in the dentate gyrus. Using a rat model of complex febrile seizures, which are thought to be a precipitating insult of TLE later in life, we report that aberrant migration of neonatal-generated granule cells results in granule cell ec...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.2850

    authors： Koyama R,Tao K,Sasaki T,Ichikawa J,Miyamoto D,Muramatsu R,Matsuki N,Ikegaya Y

    更新日期：2012-08-01 00:00:00

  • Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    abstract：:Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the ing...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm.3994

    authors： Suárez-Zamorano N,Fabbiano S,Chevalier C,Stojanović O,Colin DJ,Stevanović A,Veyrat-Durebex C,Tarallo V,Rigo D,Germain S,Ilievska M,Montet X,Seimbille Y,Hapfelmeier S,Trajkovski M

    更新日期：2015-12-01 00:00:00

  • External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

    abstract：:Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferat...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm0298-235

    authors： Mehta D,George SJ,Jeremy JY,Izzat MB,Southgate KM,Bryan AJ,Newby AC,Angelini GD

    更新日期：1998-02-01 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

  • A20 is an antigen presentation attenuator, and its inhibition overcomes regulatory T cell-mediated suppression.

    abstract：:Regulatory T cells (T(reg) cells) suppress autoreactive immune responses and limit the efficacy of tumor vaccines; however, it remains a challenge to selectively eliminate or inhibit T(reg) cells. In this study, the zinc-finger A20, a negative regulator of the Toll-like receptor and tumor necrosis factor receptor sign...

    journal_title：Nature medicine

    pub_type： 杂志文章

    doi：10.1038/nm1721

    authors： Song XT,Evel-Kabler K,Shen L,Rollins L,Huang XF,Chen SY

    更新日期：2008-03-01 00:00:00