Beyond immune checkpoint blockade: emerging immunological strategies.

The success of checkpoint inhibitors has accelerated the clinical implementation of a vast mosaic of single agents and combination immunotherapies. However, the lack of clinical translation for a number of immunotherapies as monotherapies or in combination with checkpoint inhibitors has clarified that new strategies must be employed to advance the field. The next chapter of immunotherapy should examine the immuno-oncology therapeutic failures, and consider the complexity of immune cell-cancer cell interactions to better design more effective anticancer drugs.

An aberrant STAT pathway is central to COVID-19.

COVID-19 is caused by SARS-CoV-2 infection and characterized by diverse clinical symptoms. Type I interferon (IFN-I) production is impaired and severe cases lead to ARDS and widespread coagulopathy. We propose that COVID-19 pathophysiology is initiated by SARS-CoV-2 gene products, the NSP1 and ORF6 proteins, leading to a catastrophic cascade of failures.

Author Correction: Fcmr regulates mononuclear phagocyte control of anti-tumor immunity.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Choline acetyltransferase-expressing T cells are required to control chronic viral infection.

Although widely studied as a neurotransmitter, T cell-derived acetylcholine (ACh) has recently been reported to play an important role in regulating immunity. However, the role of lymphocyte-derived ACh in viral infection is unknown. Here, we show that the enzyme choline acetyltransferase (ChAT), which catalyzes the rate-limiting step of ACh production, is robustly induced in both CD4 and CD8 T cells during lymphocytic choriomeningitis virus (LCMV) infection in an IL-21-dependent manner.

AhR controls redox homeostasis and shapes the tumor microenvironment in BRCA1-associated breast cancer.

Cancer cells have higher reactive oxygen species (ROS) than normal cells, due to genetic and metabolic alterations. An emerging scenario is that cancer cells increase ROS to activate protumorigenic signaling while activating antioxidant pathways to maintain redox homeostasis. Here we show that, in basal-like and BRCA1-related breast cancer (BC), ROS levels correlate with the expression and activity of the transcription factor aryl hydrocarbon receptor (AhR).

Early-life stress has sex-specific effects on immune function in adult song sparrows.

Multiple components of the immune system are modulated by environmental factors, including exposure to stressors. In particular, chronic stressors can impair development of the immune system, leading to alterations in immune function in adulthood. While these effects have been well established in mammals, less is known about how developmental stress modulates immunity in nonmammalian species.

Developmental stress, condition, and birdsong: a case study in song sparrows.

Sexual-selection theory posits that ornaments and displays can reflect a signaler's condition, which in turn is affected both by recent and developmental conditions. Moreover, developmental conditions can induce correlations between sexually selected and other traits if both types of traits exhibit developmental phenotypic plasticity in response to stressors. Thus, sexually selected traits may reflect recent and/or developmental characteristics of signalers.

Developmental timing of signals affects information content: song complexity but not consistency reflects innate immune strategy in male song sparrows.

In short-lived animals, innate immunity is an important component of fitness and quality. Although receivers cannot generally assess a signaler's immune function directly, sexually selected displays such as birdsong may reflect past or current condition. We investigated the degree to which song complexity and consistency, thought to reflect condition over different developmental timescales, predict multiple aspects of innate immunity in male song sparrows (Melospiza melodia).