Volume 23 Issue 2, February 2017

Immune-related adverse effects are understudied and not easily treatable risks of cancer immunotherapy. Concerted research efforts to understand the mechanisms of immunotherapy-triggered responses are crucial for developing better treatments.

A study in mouse models of allogeneic stem cell transplantation with donor-derived CD19 chimeric antigen receptor (CAR) T cells for the treatment of relapsed B cell malignancies indicates that T cell exhaustion might have a role in preventing allogeneic reactivity of CD19 CAR T cells.

In a recent study in mice, it is shown that circadian oscillations in genomic histone deactylase 3 (HDAC3) occupancy influence fuel switching and carbon flux in muscle to regulate glucose homeostasis and exercise performance.

μ opioid receptors (MORs) expressed on primary afferent nociceptor neurons are responsible for two maladaptive side-effects of chronic opioid use: opioid tolerance and opioid-induced hyperalgesia (pain). A combination therapy of opioid receptor agonism plus peripheral-restricted MOR antagonism abrogates these side-effects while preserving opioid analgesia in rodent models of peri-operative and chronic pain.

Differential expression of inflammasome gene modules and inflammasome-activating metabolites correlates with interleukin-1β expression, hypertension, arterial stiffness and longevity in older individuals.

Florian Klein and colleagues report that treating viremic HIV-1-infected individuals with the broadly neutralizing antibody 10-1074 reduced virus levels in blood, but antibody-resistant virus did emerge.

New vaccine approaches that safely elicit immunity are needed to protect against infectious disease. Erasmus et al. report their development of an insect-virus-based platform that they use to engineer a protective vaccine against chikungunya fever.

Loss of the metalloproteinase Adamts1 leads to aortic pathology in mice due to increased NOS2-dependent NO production. Decreased Adamts1 expression, associated with increased NOS2 expression, occurs in Marfan syndrome (MFS) mice and in MFS patients, and NOS2 inhibition prevents and reverses aortic pathology in MFS mice.

A pharmacological screen has identified the histone methyltransferase G9a as a target to reactivate imprinted genes in a mouse model of Prader–Willi Syndrome that improves growth and survival.

Genetic deletion of HDAC3, a circadian epigenome regulator, specifically in skeletal muscle alters amino acid metabolism, leading to increased muscle endurance but at the cost of whole-body insulin resistance.

Using a device implanted in KRAS-driven pancreatic tumors, authors demonstrate that cancer cells incorporate proteins in their microenvironment as a source of amino acids. This work provides a novel approach to study tumor metabolism that could be applied with therapeutic purposes.

Allogeneic chimeric antigen receptor (CAR) T cells are capable of inducing graft-versus-host disease (GVHD) in recipients, yet this is not commonly seen in the clinic. Marcel van den Brink, Michel Sadelain and colleagues show that alloreactive CAR T cells have reduced effector function due to signaling through the CAR and T cell receptor, resulting in reduced GVHD, while the graft-versus-leukemia effect is maintained by non-alloreactive CAR T cells.

The therapeutic response of acute myeloid leukemia to the nucleoside analog Ara-C is controlled by SAMHD1, an enzyme that hydrolyzes the active metabolite Ara-CTP.

The therapeutic response of acute myelogenous leukemia to the nucleoside analog ara-C is controlled by SAMHD1, an enzyme that hydrolyzes the activemetabolite ara-CTP.