From mice to humans: Developments in cancer immunoediting

Cancer immunoediting explains the dual role by which the immune system can both suppress and/or promote tumor growth. Although cancer immunoediting was first demonstrated using mouse models of cancer, strong evidence that it occurs in human cancers is now accumulating. In particular, the importance of CD8+ T cells in cancer immunoediting has been shown, and more broadly in those tumors with an adaptive immune resistance phenotype. This Review describes the characteristics of the adaptive immune resistance tumor microenvironment and discusses data obtained in mouse and human settings. The role of other immune cells and factors influencing the effector function of tumor-specific CD8+ T cells is covered. We also discuss the temporal occurrence of cancer immunoediting in metastases and whether it differs from immunoediting in the primary tumor of origin

Tumour invasiveness, the local and systemic environment and the basis of staging systems in colorectal cancer

background: The present study aimed to examine the relationship between tumour invasiveness (T stage), the local and systemic environment and cancer-specific survival (CSS) of patients with primary operable colorectal cancer. methods: The tumour microenvironment was examined using measures of the inflammatory infiltrate (Klintrup-Makinen (KM) grade and Immunoscore), tumour stroma percentage (TSP) and tumour budding. The systemic inflammatory environment was examined using modified Glasgow Prognostic Score (mGPS) and neutrophil:lymphocyte ratio (NLR). A 5-year CSS was examined. results: A total of 331 patients were included. Increasing T stage was associated with colonic primary, N stage, poor differentiation, margin involvement and venous invasion (P<0.05). T stage was significantly associated with KM grade (P=0.001), Immunoscore (P=0.016), TSP (P=0.006), tumour budding (P<0.001), and elevated mGPS and NLR (both P<0.05). In patients with T3 cancer, N stage stratified survival from 88 to 64%, whereas Immunoscore and budding stratified survival from 100 to 70% and from 91 to 56%, respectively. The Glasgow Microenvironment Score, a score based on KM grade and TSP, stratified survival from 93 to 58%. conclusions: Although associated with increasing T stage, local and systemic tumour environment characteristics, and in particular Immunoscore, budding, TSP and mGPS, are stage-independent determinants of survival and may be utilised in the staging of patients with primary operable colorectal cancer

Resposta de biótipos de Borreria latifolia do Sudoeste do Paraná e Norte de Santa Catarina ao herbicida glyphosate.

A erva-quente (Borreria latifolia) tem sido uma das principais espécies selecionadas pelo herbicida glyphosate em lavoura de soja nos estados do Paraná e Santa Catarina. O objetivo deste trabalho foi avaliar a resposta de biótipos de ervaquente ao glyphosate. O experimento foi realizado em casa de vegetação, em delineamento experimental completamente casualizado, com quatro repetições. Os tratamentos constituíram-se de doses crescentes de glyphosate (0, 74, 163, 360, 792 e 1742 g e.a. ha-1), aplicadas sobre quatorze biótipos de erva-quente oriundos de lavouras de soja RR do Sudoeste do Paraná e Norte de Santa Catarina. Foram avaliados o controle e a massa da parte aérea seca (MPAS). Os resultados indicam variabilidade de resposta ao glyphosate entre os biótipos coletados. Os biótipos 277, 283 e 300 não foram controlados com dose acima da usualmente utilizada nas lavouras, evidenciando seleção pelo uso repetitivo de herbicida

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

General Gauge Mediation at the Weak Scale

We completely characterize General Gauge Mediation (GGM) at the weak scale by solving all IR constraints over the full parameter space. This is made possible through a combination of numerical and analytical methods, based on a set of algebraic relations among the IR soft masses derived from the GGM boundary conditions in the UV. We show how tensions between just a few constraints determine the boundaries of the parameter space: electroweak symmetry breaking (EWSB), the Higgs mass, slepton tachyons, and left-handed stop/sbottom tachyons. While these constraints allow the left-handed squarks to be arbitrarily light, they place strong lower bounds on all of the right-handed squarks. Meanwhile, light EW superpartners are generic throughout much of the parameter space. This is especially the case at lower messenger scales, where a positive threshold correction to $m_h$ coming from light Higgsinos and winos is essential in order to satisfy the Higgs mass constraint.Comment: 43 pages, 20 figures, mathematica package included in the sourc

Testing the theory of immune selection in cancers that break the rules of transplantation

Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance