A local human Vδ1 T cell population is associated with survival in nonsmall-cell lung cancer

Murine tissues harbor signature γδ T cell compartments with profound yet differential impacts on carcinogenesis. Conversely, human tissue-resident γδ cells are less well defined. In the present study, we show that human lung tissues harbor a resident Vδ1 γδ T cell population. Moreover, we demonstrate that Vδ1 T cells with resident memory and effector memory phenotypes were enriched in lung tumors compared with nontumor lung tissues. Intratumoral Vδ1 T cells possessed stem-like features and were skewed toward cytolysis and helper T cell type 1 function, akin to intratumoral natural killer and CD8+ T cells considered beneficial to the patient. Indeed, ongoing remission post-surgery was significantly associated with the numbers of CD45RA−CD27− effector memory Vδ1 T cells in tumors and, most strikingly, with the numbers of CD103+ tissue-resident Vδ1 T cells in nonmalignant lung tissues. Our findings offer basic insights into human body surface immunology that collectively support integrating Vδ1 T cell biology into immunotherapeutic strategies for nonsmall cell lung cancer

Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue

Objectives: To investigate the proliferative activity of the mammary gland epithelium and plasma levels of progesterone, estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) in premenopausal women treated with 10 and 20 mg of tamoxifen (TAM) for 22 days. Patients and methods: A randomized double-blind study was performed with 43 premenopausal women with a diagnosis of fibroadenoma of the breast. the patients were divided into three groups: A (n = 15, placebo); B (n = 15, TAM 10 mg/day) and C (n = 13, TAM 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Lumpectomy was performed on the 22nd day of therapy. Normal breast tissue samples were collected during surgery, immediately immersed in 10% buffered formalin, processed for routine histology and immunohistochemistry for proliferating cell nuclear antigen (PCNA) detection. Two peripheral blood samples were collected, both on the 22nd day of the menstrual cycle, in order to evaluate the hormone levels. PCNA expressing epithelial cells were quantified by using a digital program Kontron Image System KS-300 in 1000 cells (400 x). Results: the percentage of cells expressing PCNA was significantly higher in the group receiving placebo (group A, 50.3%) when compared to groups receiving TAM 10 or 20 mg/day (group B, 24.1%; and group C, 23.2%, respectively) (P < 0.001). Differences between groups B and C were not significant. Levels of progesterone, estradiol and SHBG were significantly higher in B and C groups compared to group A. Increasing concentrations of FSH (P < 0.0045) and lower levels of prolactin (P < 0.0055) were only found in the group receiving 20 mg/day of TAM (group C). Conclusions: A 22-day TAM therapy, either with 10 or 20 mg/day, significantly reduced the PCNA expression and therefore the proliferative activity of the normal human breast tissue. Increasing levels of estradiol, progesterone and SHBG were associated with TAM therapy at 10 or 20 mg/day. However, a significant change of the level of FSH and prolactin was reached only with a 20-mg/day dose. (C) 1999 International Federation of Gynecology and Obstetrics.Universidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilWeb of Scienc

The Maximum Lq-likelihood method: an application to extreme quantile estimation in finance

Estimating financial risk is a critical issue for banks and insurance companies.Recently, quantile estimation based on extreme value theory (EVT) has founda successful domain of application in such a context, outperforming other methods.Given a parametric model provided by EVT, a natural approach is maximumlikelihood estimation. Although the resulting estimator is asymptotically efficient,often the number of observations available to estimate the parameters of the EVTmodels is too small to make the large sample property trustworthy. In this paper,we study a new estimator of the parameters, the maximum Lq-likelihood estimator(MLqE), introduced by Ferrari and Yang (Estimation of tail probability via themaximum Lq-likelihood method, Technical Report 659, School of Statistics, Universityof Minnesota, 2007 http://www.stat.umn.edu/~dferrari/research/techrep659.pdf).We show that the MLqE outperforms the standard MLE, when estimating tail probabilitiesand quantiles of the generalized extreme value (GEV) and the generalizedPareto (GP) distributions. First, we assess the relative efficiency between the MLqEand the MLE for various sample sizes, using Monte Carlo simulations. Second, weanalyze the performance of the MLqE for extreme quantile estimation using realworldfinancial data. The MLqE is characterized by a distortion parameter q andextends the traditional log-likelihood maximization procedure. When q different from 1, thenew estimator approaches the traditional maximum likelihood estimator (MLE),recovering its desirable asymptotic properties; when q = 1 and the sample size ismoderate or small, the MLqE successfully trades bias for variance, resulting in anoverall gain in terms of accuracy (mean squared error)

An Application of Extreme Value Theory for Measuring Financial Risk

extreme value theory, generalized pareto distribution, generalized extreme value distribution, quantile estimation, risk measures, maximum likelihood estimation, profile likelihood confidence intervals,