Abstract：
:The idea that chemotherapy can be used in combination with immunotherapy may seem somewhat counterproductive, as it can theoretically eliminate the immune cells needed for antitumour immunity. However, much preclinical work has now demonstrated that in addition to direct cytotoxic effects on cancer cells, a proportion of DNA damaging agents may actually promote immunogenic cell death, alter the inflammatory milieu of the tumour microenvironment and/or stimulate neoantigen production, thereby activating an antitumour immune response. Some notable combinations have now moved forward into the clinic, showing promise in phase I-III trials, whereas others have proven toxic, and challenging to deliver. In this review, we discuss the emerging data of how DNA damaging agents can enhance the immunogenic properties of malignant cells, focussing especially on immunogenic cell death, and the expansion of neoantigen repertoires. We discuss how best to strategically combine DNA damaging therapeutics with immunotherapy, and the challenges of successfully delivering these combination regimens to patients. With an overwhelming number of chemotherapy/immunotherapy combination trials in process, clear hypothesis-driven trials are needed to refine the choice of combinations, and determine the timing and sequencing of agents in order to stimulate antitumour immunological memory and improve maintained durable response rates, with minimal toxicity.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Brown JS,Sundar R,Lopez Jdoi
10.1038/bjc.2017.376subject
Has Abstractpub_date
2018-02-06 00:00:00pages
312-324issue
3eissn
0007-0920issn
1532-1827pii
bjc2017376journal_volume
118pub_type
杂志文章,评审abstract：:The sera from patients with advanced cancer were tested for their specific inhibitory effects on the cytotoxicity of autologous lymphocytes on tumour cells in a microculture assay. By adding a standard volume of the sera to suspensions of well-washed lymphocytes the inhibitory effect was quantitated by comparison with...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1973.67
更新日期：1973-07-01 00:00:00
abstract：:Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci were detected at low frequencies (<20%) among 69 pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, 30 other lymphoproliferative disorders (LPD) and 44 non-LPD. The incidence of individual Chlamydiae was generally higher in MALT lymphoma tha...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603981
更新日期：2007-10-08 00:00:00
abstract：:Chemotherapy or radiotherapy often cause mucosal damage in the gut (gut mucositis) in cancer patients. As a step to investigate mechanisms underlying subsequent intestinal repair, we have examined the expression profiles of hepatocyte growth factor (HGF) and its receptor c-met, two molecules previously implicated in t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1054/bjoc.1999.1023
更新日期：2000-02-01 00:00:00
abstract：BACKGROUND:Dulanermin (rhApo2L/TRAIL) induces apoptosis by binding to death receptors DR4 and DR5, leading to caspase activation and subsequent cell death. A Phase1a trial evaluated the safety and tolerability of dulanermin in patients with advanced tumours. One aim was to develop and validate pharmacodynamic biomarker...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2011.456
更新日期：2011-12-06 00:00:00
abstract：:The evidence base for head and neck cancers is low with relatively few randomized controlled trials of the two main treatments, surgery and radiotherapy. The aim of the study was to investigate the patterns of surgery and radiotherapy treatment for head and neck cancers in three large areas of England and to investiga...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690695
更新日期：1999-09-01 00:00:00
abstract：:In the present study the putative chemopreventive effect of dietary fish oil (MaxEPA) on azaserine-induced pancreatic carcinogenesis in rats was investigated. Groups of rats were maintained on a semipurified low-fat (LF; 5 wt%) diet or on semipurified high-fat (HF; 25 wt%) diets containing 5 wt% linoleic acid (LA) and...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.7
更新日期：1996-01-01 00:00:00
abstract：:Periodate-treated, non-anticoagulant heparin-carrying polystyrene consists of about ten periodate-oxidized, alkaline-degraded low molecular weight-heparin chains linked to a polystyrene core and has a markedly lower anti-coagulant activity than heparin. In this study, we evaluated the effect of non-anticoagulant hepar...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600307
更新日期：2002-06-05 00:00:00
abstract：:Four-hundred-forty-five husbands of women with invasive cervical carcinoma, 165 of women with in situ cervical cancer, and 717 of control women (age range 19-82 years) were interviewed and a sample of exfoliated cells from the penis obtained in seven case-control studies conducted by the International Agency for Resea...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600194
更新日期：2002-03-04 00:00:00
abstract：BACKGROUND:Sindbis virus (SIN) infection causes no or only mild symptoms (fever, rash, and arthralgia) in humans. However, SIN has a strong cytopathic effect (CPE) on various cancer cells. This study focuses on the oncolytic activity of SIN AR399 on oral cancer cells compared with reovirus, a well-known oncolytic virus...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605209
更新日期：2009-08-18 00:00:00
abstract：BACKGROUND:Overexpression of ErbB2 receptor in breast cancer is associated with disease progression and poor prognosis. Trastuzumab, the only humanised anti-ErbB2 antibody currently used in breast cancer, has proven to be effective; however, a relevant problem for clinical practice is that a high fraction of breast can...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6605499
更新日期：2010-02-02 00:00:00
abstract：:To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the l...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1996.663
更新日期：1996-12-01 00:00:00
abstract：:Secular, socioeconomic and urban-rural gradients and geographical differences in beef and fat consumption within the United States of America are compared with corresponding data on colorectal cancer incidence and mortality rates. These results, together with the results of most previous epidemiological studies, appea...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1975.244
更新日期：1975-10-01 00:00:00
abstract：BACKGROUND:Antihypertensives may inhibit pancreatic carcinogenesis. We examined the association between use of these drugs and pancreatic cancer in patients with chronic pancreatitis. METHODS:We conducted a nationwide population-based cohort study of all chronic pancreatitis patients diagnosed in Denmark during 1996-2...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0562-y
更新日期：2019-10-01 00:00:00
abstract：:Recent investigations have increasingly focussed attention on the roles of intracellular vesicle trafficking in the regulation of epithelial polarity and transformation. Rab25, an epithelial-specific member of the Rab family of small GTPases, has been associated with several epithelial cancers. Whereas Rab25 overexpre...
journal_title：British journal of cancer
pub_type： 杂志文章,评审
doi：10.1038/sj.bjc.6605983
更新日期：2011-01-04 00:00:00
abstract：:Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604152
更新日期：2008-03-25 00:00:00
abstract：:Prostate cancer is the second leading cause of male death from malignant disease in Europe and in the USA. Failure to prevent or eliminate metastatic dissemination is a fundamental problem underlying the current inadequate treatment of prostate cancer, and novel therapeutic strategies are required if this disease is t...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1998.45
更新日期：1998-01-01 00:00:00
abstract：:Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1980.174
更新日期：1980-06-01 00:00:00
abstract：:Astrocytomas develop intense vascular proliferation, essential for tumour growth and invasiveness. Angiotensin II (ANGII) was initially described as a vasoconstrictor; recent studies have shown its participation in cellular proliferation, vascularisation, and apoptosis. We conducted a prospective study to evaluate the...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6604431
更新日期：2008-07-08 00:00:00
abstract：:Multidrug resistance (MDR) is the major confounding factor in adjuvant solid tumour chemotherapy. Increasing intracellular amounts of chemotherapeutics to circumvent MDR may be achieved by a novel delivery method, photochemical internalisation (PCI). PCI consists of the co-administration of drug and photosensitiser; u...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603895
更新日期：2007-08-20 00:00:00
abstract：BACKGROUND:Type 2 diabetes mellitus and high total cholesterol and triglycerides are known to be associated with increased colorectal cancer risk for the general population. These associations are unknown for people with a germline DNA mismatch repair gene mutation (Lynch syndrome), who are at high risk of colorectal c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/s41416-019-0580-9
更新日期：2019-11-01 00:00:00
abstract：:Women referred to a familial breast cancer clinic completed questionnaires before and after counselling and at annual follow-up to assess their risk estimate and psychological characteristics. The aims were to determine whether those who attended the clinic overestimated their risk or were highly anxious and whether c...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6690078
更新日期：1999-02-01 00:00:00
abstract：BACKGROUND:The role of telomerase reverse transcriptase (TERT) in gliomagenesis has been recently further strengthened by the frequent occurrence of TERT promoter mutations (TERTp-mut) in gliomas and evidence that the TERT SNP genetic rs2736100 influences glioma risk. TERTp-mut creates a binding site for Ets/TCF transc...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2014.538
更新日期：2014-11-11 00:00:00
abstract：BACKGROUND:Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). METHODS:The national registry-based case-con...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.2015.53
更新日期：2015-03-17 00:00:00
abstract：:Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test is currently of sufficient sensitivity or sp...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6603188
更新日期：2006-06-19 00:00:00
abstract：:The incidence of Kaposi's sarcoma (KS) in 1976-90 was assessed in Italy, taking advantage of a network of nine population-based cancer registries covering, at its maximum, approximately 5.6 million subjects. The first examined period (1976-84) substantially reflects the epidemiology of KS prior to the AIDS epidemic in...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1994.60
更新日期：1994-02-01 00:00:00
abstract：:Interleukin 6 (IL-6) and its soluble receptor (IL-6sR) can markedly stimulate aromatase activity in cultured fibroblasts derived from normal or malignant breast tissues. IL-6 acts by binding to a low-affinity membrane-spanning receptor (IL-6R), which must associate with a high-affinity receptor (gp130) for signal tran...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/sj.bjc.6600785
更新日期：2003-02-24 00:00:00
abstract：:The photodynamic effects of sulphonated aluminium phthalocyanine (SALPC) have been compared on cultured AR4-2J cells of a pancreatic carcinoma cell line and on exocrine cells of the normal phenotype freshly isolated from the rat pancreas; a multi-channel perifusion system was used for this kinetic study in vitro. Wher...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1990.157
更新日期：1990-05-01 00:00:00
abstract：:A correction to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：British journal of cancer
pub_type： 已发布勘误
doi：10.1038/s41416-019-0505-7
更新日期：2019-07-01 00:00:00
abstract：:Rhizoxin is a tubulin-binding anti-neoplastic agent which is active in a range of murine tumour models. The recommended schedule, of intravenous (i.v.) bolus administration at a dose of 2 mg m-2 every 3 weeks, has been assessed in three phase II trials of ovarian, renal and colorectal cancer. In general terms the drug...
journal_title：British journal of cancer
pub_type： 临床试验,杂志文章
doi：10.1038/bjc.1995.498
更新日期：1995-11-01 00:00:00
abstract：:Squamous cell carcinomas of the anus are rare neoplasias that account for about 3% of large bowel tumours. Infections with human papillomaviruses are frequently detected in these cancers, suggesting that pathogenic pathways in anal carcinomas and in carcinomas of the uterine cervix are similar. Little is known regardi...
journal_title：British journal of cancer
pub_type： 杂志文章
doi：10.1038/bjc.1997.547
更新日期：1997-01-01 00:00:00
