TRL conceived the study, participated in the design and prepared the manuscript. PM performed immunohistochemical analysis of tumours microarrays and prepared the manuscript. MJP conceived the study, participated in the design and prepared the manuscript. All find more authors read and approved the final manuscript.”
“Background Colorectal cancer is estimated to cause 639,000 deaths world wide per year [1]. The prognosis following surgery depends on disease stage, and this also determines the need for additional treatment. However clinico-pathological stage characteristics alone provide imperfect prognostic information. For example, approximately 25% of patients with disease localised

to the primary site (UICC Stage I and II) relapse after surgery and may have benefited from adjuvant therapy Selleckchem GDC0449 [2], whereas 25% of patients with regional lymph node metastases (UICC Stage III) are cured by surgery alone [3]. Various ways to improve the prognostic accuracy of staging include increasing the number of lymph nodes analysed [4, 5], increasing the sensitivity of the tests used to detect lymph node metastases [6] and using microarray technology to analyse gene expression [7, 8]. However these methods do not take onto account potentially important host-related factors such as the immune response. The immune response

has long been associated CX-5461 ic50 with eradication of tumours [9]. More recently, it has become clear that T cells in the tumour are positively associated with good patient prognosis [10, 11] in colorectal cancer. CD4 or CD8+ T cells expressing IFNγ, or the IFNγ inducing transcription factor Tbet, are the cells most likely involved at the tumour site [12, 13]. In immune responses to infection, the effector CD4 and CD8 T cell populations are held in check by a third population of cells – regulatory T cells (Tregs). While there are numerous subtypes of T cells with regulatory function, the majority

of suppressive function is mediated by Foxp3+ CD4+ Tregs. As expected, low numbers of MEK inhibitor these Foxp3+ Tregs have been associated with improved patient outcome in breast and colorectal cancers [14–16]. However, some authors report an association between high numbers of Tregs and positive patient outcome [17, 18], although Salama et al found a negative association between patient outcome and high frequency of Tregs in the non-tumour associated tissue [18]. More recently, Chaput et al identified a population of CD8+Foxp3+ T cells in a cohort of colorectal cancer patients that had suppressive activity and were proposed to mediate tumour escape [19]. The immune response is initiated in the lymph nodes, and although analyses of T cell subsets in the lymph nodes of breast cancer patients have been performed [20], the effect of these T cell subsets on colorectal cancer patient outcome had not been explored.