Hepatocytes coordinate immune evasion in cancer via release of serum amyloid A proteins.

T cell infiltration into tumors is a favorable prognostic feature, but most solid tumors lack productive T cell responses. Mechanisms that coordinate T cell exclusion are incompletely understood. Here we identify hepatocyte activation via interleukin-6/STAT3 and secretion of serum amyloid A (SAA) proteins 1 and 2 as important regulators of T cell surveillance of extrahepatic tumors.

Multimodal immune phenotyping reveals microbial-T cell interactions that shape pancreatic cancer.

Microbes are an integral component of the tumor microenvironment. However, determinants of microbial presence remain ill-defined. Here, using spatial-profiling technologies, we show that bacterial and immune cell heterogeneity are spatially coupled.

Cancer immunotherapy via synergistic coactivation of myeloid receptors CD40 and Dectin-1.

Myeloid cells facilitate T cell immune evasion in cancer yet are pliable and have antitumor potential. Here, by cotargeting myeloid activation molecules, we leveraged the myeloid compartment as a therapeutic vulnerability in mouse models of pancreatic cancer. Myeloid cells in solid tumors expressed activation receptors including the pattern recognition receptor Dectin-1 and the TNF receptor superfamily member CD40.

First, do no harm: why anti-immigrant policies in the United States are a public health concern.

It can be argued that anti-immigrant policies, such as the 287(g) program, can have a direct impact on the health and well-being of the immigrant community in general, particularly undocumented immigrants in the United States. While there is yet to be a comprehensive and conclusive empirical assessment of this issue, what is known is that the immigrant community faces many stress factors and structural barriers that negatively impact health. We argue that it is urgent that public health responds to the unique experiences and challenges of the undocumented and wider immigrant community.

TNF blockade uncouples toxicity from antitumor efficacy induced with CD40 chemoimmunotherapy.

Agonist CD40 antibodies are under clinical development in combination with chemotherapy as an approach to prime for antitumor T cell immunity. However, treatment with anti-CD40 is commonly accompanied by both systemic cytokine release and liver transaminase elevations, which together account for the most common dose-limiting toxicities. Moreover, anti-CD40 treatment increases the potential for chemotherapy-induced hepatotoxicity.

Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.

Agonistic anti-CD40 monoclonal antibody (mAb) therapy in combination with chemotherapy (chemoimmunotherapy) shows promise for the treatment of pancreatic ductal adenocarcinoma (PDA). To gain insight into immunological mechanisms of response and resistance to chemoimmunotherapy, we analyzed blood samples from patients (n = 22) with advanced PDA treated with an anti-CD40 mAb (CP-870,893) in combination with gemcitabine. We found a stereotyped cellular response to chemoimmunotherapy characterized by transient B cell, CD56+CD11c+HLA-DR+CD141+ cell, and monocyte depletion and CD4+ T cell activation.

Risk and protective factors related to alcohol and drug use amongst American Indian youth: An application of the social development model.

The goal of this study is to assess the relevance of the Social Development Model (SDM) in predicting substance use across American Indian (AI) youth. We rely on self-reported data collected as part of the 2004 Arizona Youth Survey (AYS). The final sample included 2,912 AI students from 169 schools in 15 counties.

A study of firesetting and animal cruelty in children: family influences and adolescent outcomes.

Objective: To investigate relationships among family risk factors, childhood firesetting and animal cruelty, and adolescent delinquency.

Method: In 1990, mothers and children participating in a 10-year prospective study provided information about family risk factors and childhood problem behavior. Subsequent interviews with 86% of the sample in 1996 and 1998 and court record reviews in 2000 provided information about juvenile delinquency.

Sexual abuse, family violence, and female delinquency: findings from a longitudinal study.

The current study examines the effects of three forms of childhood victimization on self-reported delinquency and aggression in adolescent girls. These analyses are based on a longitudinal sample of 141 mother-daughter pairs participating in a study about marital violence and child development. When the children were school aged, mothers and children provided reports describing (a) child exposure to marital violence, (b) escalated physical abuse against the child, and (c) child sexual abuse.