Antiviral cellular immunity in colorectal cancer patients

Kiewe, Philipp; Wojtke, Susanne; Thiel, Eckhard; Nagorsen, Dirk

doi:10.1016/j.humimm.2008.12.004

Cited by 4 publications

(3 citation statements)

References 20 publications

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“…These responses were lowest in those with haematological malignancies and breast carcinoma. It has been shown previously that patients with colorectal carcinomas did not have any significant reduction in CMV-and influenza-specific T-cell responses (Kiewe et al, 2009), assessed using MHC class I tetramers. However, as detection of antigen-specific cells by tetramers does not depend on T-cell function, it is not clear whether the antiviral T cells of these patients were functionally similar to healthy controls.…”

Section: Discussionmentioning

confidence: 90%

IE63-specific T-cell responses associate with control of subclinical varicella zoster virus reactivation in individuals with malignancies

et al. 2010

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BACKGROUND: Reactivation of the varicella zoster virus (VZV) is more common in patients with malignancies; however, the molecular and cellular mechanisms underlying this susceptibility are unclear. METHODS: Using ex vivo interferon-g ELISpot assays, we set out to analyse VZV-specific immune responses in a large cohort of patients with malignancies. RESULTS: We observed that patients with malignancies had impaired VZV-specific T-cell responses, particularly in those with haematological malignancies and breast carcinoma. Immediate-early protein 63 (IE63)-specific T-cell responses were significantly impaired in those with subclinical VZV re-activation. Malignancy is associated with reactivation of chronic persistent viruses such as varicella zoster virus (VZV) (Whiteside, 2006), causing significant morbidity and mortality (Wade, 2006). Herpes zoster is more common in patients with malignancies (Schmader, 2001;Sorensen et al, 2004) and may lead to severe disease with multi-dermatomal involvement and visceral dissemination, which can be lethal (Gallagher and Merigan, 1979;Onunu and Uhunmwangho, 2004;Hackanson et al, 2005;Graue et al, 2006). However, apart from clinically apparent VZV reactivation, subclinical reactivation has also been reported in both immunocompetent and immunosuppressed individuals (Schunemann et al, 1998;Quinlivan et al, 2007). Although the mechanisms underlying such reactivation are unclear, it is thought that cell-mediated immune responses are vital in controlling VZV replication (Malavige et al, , 2008b.VZV glycoproteins I and E, immediate-early protein 63 (IE63) and four specific CD4 þ T cells have been shown to circulate at persistently high frequencies in the peripheral blood of healthy seropositive donors without a history of reactivation (Jones et al, 2006Malavige et al, 2007Malavige et al, , 2008a. However, VZV-specific T-cell responses have been shown to be lower in elderly individuals and in patients with disease such as systemic lupus erythematosus (Miller, 1980;Levin et al, 2003;Park et al, 2004). As these groups of individuals are at a higher risk of herpes zoster, it seems that VZVspecific T cells are important in preventing virus reactivation. Some important studies conducted earlier have indeed shown that suppression of VZV-specific cellular immunity preceded the occurrence of herpes zoster (Arvin et al, 1978(Arvin et al, , 1980. However, with a more detailed understanding of VZV protein-specific responses, we can now study the mechanisms that are important in preventing virus reactivation. Therefore, we set out to analyse the overall VZV-specific immune responses and the immune responses to VZV IE63 and gE proteins, in a cohort of patients with malignancies to identify the associations with viral reactivation. MATERIALS AND METHODSFresh heparinised venous blood samples were obtained from 106 adult individuals with malignancies (before receiving chemotherapy) who were admitted to the Cancer Institute in Sri Lanka with a past history of primary VZV infection. Samples were also obt...

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Section: Discussionmentioning

confidence: 90%

IE63-specific T-cell responses associate with control of subclinical varicella zoster virus reactivation in individuals with malignancies

et al. 2010

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“…Recombinant adenovirus vaccines are compatible with conventional high-dose chemotherapy and that the combined treatment resulted in improved therapeutic outcomes relative to either agent individually [128]. Although a firm conclusion cannot be drawn on T-cell induction in cancer patients during vaccination therapy, results show that CRC patients retain their antiviral T cells, suggesting a potential susceptibility to immunotherapy [129]. Strategies have improved because of advances in the characterization of tumor-associated antigens, the development of improved vaccine delivery systems, and the combination of vaccines with cytokines and other immunostimulants to enhance immune responses [130].…”

Section: Combinatorial Approachmentioning

confidence: 99%

Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis

Mishra

Drummond²,

Quazi

et al. 2013

Critical Reviews in Oncology/Hematology

161

117

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Colorectal cancer is the leading cause of cancer-related mortality in the western world. It is also the third most common cancer diagnosed in both men and women in the United States with a recent estimate for new cases of colorectal cancer in the year 2012 being around 103,170. Various risk factors for colorectal cancer include life-style, diet, age, personal and family history, and racial and ethnic background. While a few cancers are certainly preventable but this does not hold true for colon cancer as it is often detected in its advanced stage and generally not diagnosed until symptoms become apparent. Despite the fact that several options are available for treating this cancer through surgery, chemotherapy, radiation therapy, immunotherapy, and nutritional-supplement therapy, but the success rates are not very encouraging when used alone where secondary complications appear in almost all these therapies. To maximize the therapeutic-effects in patients, combinatorial approaches are essential. In this review we have discussed the therapies previously and currently available to patients diagnosed with colorectal-cancer, focus on some recent developments in basic research that has shaded lights on new therapeutic-concepts utilizing macrophages/dendritic cells, natural killer cells, gene delivery, siRNA-, and microRNA-technology, and specific-targeting of tyrosine kinases that are either mutated or over-expressed in the cancerous cell to treat these cancer. Potential strategies are discussed where these concepts could be applied to the existing therapies under a comprehensive approach to enhance the therapeutic effects.

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“…Many investigators relate the immune dysfunction of cancer patients with both the inefficient anti-tumor response and a reduced efficacy of immunotherapy [19,20]. To this end, we have recently identified that patients with lung cancer present with a tenfold higher number of anti-tumor CTL as compared to the age-matched controls [13].…”

Section: Discussionmentioning

confidence: 99%

Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

Karanikas

Ζαμανάκου

Soukou

et al. 2010

J Exp Clin Cancer Res

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BackgroundThis study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence.MethodsPeripheral blood mononuclear cells from lung cancer patients, age-matched and younger healthy individuals were used to measure EBV-specific CTLs after in vitro amplification with the GLCTLVAML and RYSIFFDYM peptides followed by HLA-multimer staining.ResultsLung cancer patients and aged-matched controls had significantly lesser EBV-specific CTL than younger healthy individuals. Multimer positive populations from either group did not differ with respect to the percentage of multimer positive CTLs and the intensity of multimer binding.ConclusionsThis study provides evidence that patients with lung cancer exhibit an EBV-specific CTL response equivalent to that of age-matched healthy counterparts. These data warrant the examination of whether young individuals have a more robust anti-tumor response, as is the case with the anti-EBV response.

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Antiviral cellular immunity in colorectal cancer patients

Cited by 4 publications

References 20 publications

IE63-specific T-cell responses associate with control of subclinical varicella zoster virus reactivation in individuals with malignancies

IE63-specific T-cell responses associate with control of subclinical varicella zoster virus reactivation in individuals with malignancies

Prospective of colon cancer treatments and scope for combinatorial approach to enhanced cancer cell apoptosis

Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

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