Low density of CD3+, CD4+ and CD8+ cells is associated with increased risk of relapse in squamous cell cervical cancer

The purpose of this study was to investigate the prognostic value of the primary in situ cellular immune response in cervical squamous cell carcinoma. A study of 102 women treated for stage IB and IIA disease, between 1990 and 2000, was performed. Paraffin-embedded cervical tissue processed at the time of diagnosis was immunostained for CD3+ (T cells), CD4+ (T helper/regulatory T cells) and CD8+ (cytotoxic T cells) cells. Immune cell profile densities were estimated using stereology. Both intra- and peritumoural cell densities were estimated. Using Cox's proportional hazards regression modelling we found an increase in cell density to decrease the risk of relapse for all three cell types. The density of peritumoural CD3+ cells seems to have the strongest potential for predicting relapse. An increase in CD3+ cell density from 795 to 2043 cells per mm2 (25–75 percentile) reduced the hazard ratio to 0.27

CD1a-positive infiltrating-dendritic cell density and 5-year survival from human breast cancer

© Churchill LivingstoneInfiltrating CD1a+ dendritic cells (DCs) have been associated with increased survival in a number of human cancers. This study investigated DC infiltration within breast cancers and the association with survival. Classical established prognostic factors, of tumour size, lymph node status, histological grade, lympho-vascular invasion, the KI-67 (MIB-1) fraction and the Nottingham Prognostic Index (NPI) were also compared. A total of 48 breast cancer patients were followed from the time of surgery and CD1a density analysis for 5 years or until death. Our data set validated previous studies, which show a relationship between survival and the NPI (P<0.001), tumour size (P<0.01) and lymph node status (P<0.05). Although more patients were alive at the 5-year time point in the group with higher CD1a DC density than the lower CD1a DC group, this failed to reach statistical significance at the P=0.05 level. Analysis at 10 years postsurgery is required to investigate the association further.B.J.Coventry and J. Morto

Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

Lung cancer risk in painters: a meta-analysis

We conducted a meta-analysis to quantitatively compare the association between occupation as a painter and the incidence or mortality from lung cancer. PubMed and the reference lists of pertinent publications were searched and reviewed. For the meta-analysis, we used data from 47 independent cohort, record linkage, and case-control studies (from a total of 74 reports), including > 11,000 incident cases or deaths from lung cancer among painters. Three authors independently abstracted data and assessed study quality. The summary relative risk (meta-RR, random effects) for lung cancer in paint-ers was 1.35 [95% confidence interval (CI), 1.29-1.41; 47 studies] and 1.35 (95% CI, 1.21-1.51; 27 studies) after controlling for smoking. The relative risk was higher in never-smokers (meta-RR = 2.00; 95% CI, 1.09-3.67; 3studies) and persisted when restricted to studies that adjusted for other occupational exposures (meta-RR = 1.57; 95% CI, 1.21-2.04; 5 studies). These results support the conclusion that occupational exposures in painters are causally associated with the risk of lung cancer

Expression of a single, viral oncoprotein in skin epithelium is sufficient to recruit lymphocytes

Established cancers are frequently associated with a lymphocytic infiltrate that fails to clear the tumour mass. In contrast, the importance of recruited lymphocytes during premalignancy is less well understood. In a mouse model of premalignant skin epithelium, transgenic mice that express the human papillomavirus type 16 (HPV16) E7 oncoprotein under a keratin 14 promoter (K14E7 mice) display epidermal hyperplasia and have a predominant infiltrate of lymphocytes consisting of both CD4 and CD8 T cells. Activated, but not naïve T cells, were shown to preferentially traffic to hyperplastic skin with an increased frequency of proliferative CD8+ T cells and CD4+ T cells expressing CCR6 within the tissue. Disruption of the interaction between E7 protein and retinoblastoma tumour suppressor protein (pRb) led to reduced epithelial hyperplasia and T cell infiltrate. Finally, while K14E7 donor skin grafts are readily accepted onto syngeneic, non-transgenic recipients, these same skin grafts lacking skin-resident lymphocytes were rejected. Our data suggests that expression of a single oncoprotein in the epidermis is sufficient for lymphocyte trafficking (including immunosuppressive lymphocytes) to premalignant skin