Volume 23 Issue 12, December 2017

From policy advisors who resigned in protest to an agency trying to settle a patent dispute, many of the newsmakers in our 2017 Yearbook made notable decisions.

This past year included numerous research studies that broke the mold and elucidated new biology and drug targets. Here are some of the exciting papers from 2017 that moved biomedicine forward.

From a worldwide march in favor of science to an increased focus on diversity and gender equality in the workplace, 2017 was a year that was dominated by activism and social causes. Amidst these events, however, were concerns over unproven treatments and emergency funding.

In 2017, cancer drugs once again dominated the news, with many of these medications making headlines for being the first of their kind to gain approval. Beyond cancer, drugs for inflammatory diseases also received attention, for both their successes and their failures.

In an article published recently in Nature Medicine, the authors generate organoid models of liver neoplasia. In doing so, they highlight both the diversity of current organoid methodologies and their application to cancer modeling and therapeutics discovery.

Signals that govern immune cells in the heart remain poorly defined. A new report in mice shows that pathways involved in sensing viruses orchestrate monocyte and macrophage activation through recognition of DNA derived from dying cardiomyocytes following myocardial infarction.

In a recent study, Maciocia et al. develop a novel T cell receptor beta (TCRB) constant C1-chain-directed cellular immunotherapy for the treatment of T cell malignancies.

A new study shows that deleting uncoupling protein 1 activates Ca²⁺ cycling thermogenesis within beige fat, protecting mice against cold-induced hypothermia and dysglycemia following diet-induced obesity.

TGF-β induces expression of ADAM10, which results in greater shedding of ephrin-B2. This shedding promotes the chemotaxis and activation of myofibroblasts and thus the progression of organ fibrosis.

Pule and colleagues identify the TCR β-chain constant region as a new target for chimeric antigen receptor (CAR) T cells in treatment of T cell cancers while potentially preserving a healthy T cell repertoire. They demonstrate that anti-TCRB1 CAR T cells eliminate cancerous TCRB1⁺ T cells while sparing nearly one-third of normal TCRB2⁺ T cells.

Tumor organoids derived from the most common subtypes of primary liver cancer recapitulate the histologic and molecular features of the tissues of origin, even after long-term culture. These in vitro models, as well as those for colorectal cancer reported in Crespo et al. in a previous issue, are amenable for drug screening and allow the identification of therapeutic approaches with potential for cancer treatment.

Hosen et al. identify an active conformation of integrin beta-7 as a cancer-associated antigen in multiple myeloma, and engineer a CAR-T cell that shows efficacy against MM in a mouse model. These findings describe the first conformation-specific CAR-T cell and highlight the potential of conformational targets in cancer immunotherapy.

Asprosin, a recently identified secreted hormone from adipose tissue, acts centrally to promote food intake.

Calcium cycling induced by the SERCA2b–RyR2 pathway in beige fat cells allows for thermogenic activity independent of UCP1.

Screening reveals that obesity induces the expression of liver ectodysplasin A, which acts on the muscle to induce insulin resistance.

In humans, a full night of sleep deprivation causes attenuated and delayed neuronal responses that correlate with impaired cognitive performance.

The massive cell death that occurs during myocardial infarction releases self-DNA and triggers an interferon response in infiltrating leukocytes via a cGAS–STING–IRF3 pathway. Interference with this response—either by genetic disruption of the pathway or antibody blockade of the type I interferon receptor—is beneficial in mice subjected to myocardial infarction.

Genetic cell-lineage tracing studies in mice are crucial for delineating the contribution of stem and progenitor cells to different cell types, both in disease states and after regenerative therapy. He et al. have developed new genetic lineage-tracing systems that provide more definitive results than the commonly used Cre-based system and show that this new technology can resolve current controversies in the field, as demonstrated by lineage-tracing studies in the heart and liver.