The National Lung Matrix Trial is currently the largest stratified medicine study in lung cancer. Utilizing a next-generation sequencing screening platform and an adaptive umbrella trial design, we will explore the activity of multiple biomarker/targeted therapy options in order to expand the precision medicine opportunities for patients with non-small-cell lung cancer.

Both LL-37 and hBD-2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE.

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...