Activity

on of the NSE network.

ICIs have strongly improved the outcome of NSCLC patients. However, primary and secondary resistance occur during treatment in most of the patients, with several of them developing fast progressions. Autoantibodies can be related with a dysfunctional immune system, although their association with immune-based anti-cancer therapies has never been investigated. Moreover, so far no reliable predictive factor is currently available to aid in treatment selection. CD137

T-cells are largely known to be the anti-tumor activated effector cells, but they have never been associated with the response to immunotherapies.

Forty-two patients with metastatic NSCLC receiving anti-PD-1 ICIs at Sant’Andrea Hospital and Policlinico Umberto I, from June 2016 to September 2018 were enrolled. Circulating levels of IgM-Rheumatoid Factor were evaluated at baseline and correlated with patients clinical response following the anti-PD-1 treatment. IgM-RF interaction and effect on T-cells in vivo and in vitro were investigated.

Iged NSCLC patients. The ability of IgM-RF to bind naïve and central memory T-cells and impair their migration could make account for the reduction of the tumor-reactive CD137

T-cells population that may cause a non-effectiveness of these T-cells targeting drugs.

AIRC, MIUR and Sapienza University of Rome.

AIRC, MIUR and Sapienza University of Rome.

Individuals with typical circadian rhythm sleep-wake disorders (CRSWDs) have a habitual sleep timing that is desynchronized from social time schedules. However, it is possible to willfully force synchronisation against circadian-driven sleepiness, which causes other sleep problems. This pathology is distinguishable from typical CRSWDs and is referred to here as latent CRSWD (LCRSWD). Conventional diagnostic methods for typical CRSWDs are insufficient for detecting LCRSWD because sufferers have an apparently normal habitual sleep timing.

We first evaluated the reliability of circadian phase estimation based on clock gene expression using hair follicles collected at three time points without sleep interruption. Next, to identify detection criteria for LCRSWD, we compared circadian and sleep parameters according to estimated circadian phases, at the group and individual level, between subjects with low and high Pittsburgh Sleep Quality Index (PSQI) scores. this website To validate the reliability of identified detection by JSPS, Japan.

This study was supported mainly by JSPS, Japan.

Combined immune checkpoint inhibitor (ICI) treatment targeting PD-1 and CTLA-4 was suggested to yield clinical benefit over chemotherapy in malignant pleural mesothelioma (MPM), whereas aPD-1 monotherapy failed to provide benefit in phase-III trials. Success of ICI depends on the presence and activation of tumor-specific T cells. Therefore, we investigated whether T-cell characteristics are underlying clinical efficacy of ICI treatment in MPM.

Comprehensive immune cell profiling was performed on screening and on treatment peripheral blood samples of mesothelioma patients treated with nivolumab (aPD-1) monotherapy (NCT02497508), or a combination of nivolumab and ipilimumab (aCTLA-4) (NCT03048474).

aPD-1/aCTLA-4 combination treatment induced a profound increase in proliferation and activation of T cells, which was not observed upon aPD-1 monotherapy. Moreover, patients that responded to combination treatment had low frequencies of naive CD8 T cells and high frequencies of effector memory CD8 T cells that re-expressed RA (TEMRA) at screening. The frequency of Granzyme-B and Interferon-γ producing TEMRAs was also higher in responding patients.

High proportions of TEMRAs and cytokine production by TEMRAs before treatment, was associated with a better clinical outcome. TEMRAs, which likely comprise tumor-specific T cells, tend to require blockage of both aPD-1 and aCTLA-4 to be reactivated. In conclusion, peripheral blood TEMRAs can play a key role in explaining and predicting clinical benefit upon aPD-1/aCTLA-4 combination treatment.

Bristol-Myers Squibb sponsored NivoMes and INITIATE clinical trials and provided study drugs. No external funding was applicable for the flow cytometric analyses of peripheral blood samples described in this manuscript.

Bristol-Myers Squibb sponsored NivoMes and INITIATE clinical trials and provided study drugs. No external funding was applicable for the flow cytometric analyses of peripheral blood samples described in this manuscript.

α4β7 is a gut-homing integrin heterodimer that can act as a non-essential binding molecule for HIV. A previous study in heterosexual African women found that individuals with higher proportions of α4β7 expressing CD4

T cells were more likely to become infected with HIV, as well as present with faster disease progression. It is unknown if this phenomenon is also observed in men who have sex with men (MSM) or people who inject drugs (PWID).

MSM and transgender women who seroconverted as part of the HVTN 505 HIV vaccine trial and PWID who seroconverted during the ALIVE cohort study were selected as cases and matched to HIV-uninfected controls from the same studies (11 and 13, respectively). Pre-seroconversion PBMC samples from cases and controls in both studies were examined by flow cytometry to measure levels of α4β7 expression on CD4

T cells. Multivariable conditional logistic regression was used to compare α4β7 expression levels between cases and controls. A Kaplan-Meier curve was used to examine the nstitutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.

This study was supported in part by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. The study was also supported by extramural grants from NIAID T32AI102623 (E.U.P.), and UM1AI069470.

Identifying which individuals will develop tuberculosis (TB) remains an unresolved problem due to few animal models and computational approaches that effectively address its heterogeneity. To meet these shortcomings, we show that Diversity Outbred (DO) mice reflect human-like genetic diversity and develop human-like lung granulomas when infected with Mycobacterium tuberculosis (M.tb) .

Following M.tb infection, a “supersusceptible” phenotype develops in approximately one-third of DO mice characterized by rapid morbidity and mortality within 8 weeks. These supersusceptible DO mice develop lung granulomas patterns akin to humans. This led us to utilize deep learning to identify supersusceptibility from hematoxylin & eosin (H&E) lung tissue sections utilizing only clinical outcomes (supersusceptible or not-supersusceptible) as labels.

The proposed machine learning model diagnosed supersusceptibility with high accuracy (91.50 ± 4.68%) compared to two expert pathologists using H&E stained lung sections (94.