- Inflammatory niche impedes therapy targeting MAPK
Drug tolerance brought about by reversible adaptive responses precedes the emergence of irreversible mutation-driven drug resistance and sustains tumor cells when at their most vulnerable. Young et al. delineate a signaling relay incorporating IL-1 and CXCR2 ligands emanating from melanoma-associated macrophages and fibroblasts, respectively, that confer tolerance to MAPK inhibitors.
- NLRP3 promotes pancreatic oncogenesis
Daley et al. show that NLRP3 signaling in macrophages drives their immune-suppressive phenotype in the pancreatic tumor microenvironment and potentiates tolerogenic T cell differentiation. Conversely, targeting NLRP3 protects against pancreatic oncogenesis and is associated with immunogenic reprograming within the tumor.
- Heterogeneity of phagocytic macrophages
Macrophages are important for tissue function, and adapt phenotypically to each tissue by factors produced locally. A-Gonzalez et al. now show that phagocytosis of unwanted cells additionally contributes to imprinting macrophage heterogeneity, thus promoting tissue homeostasis.
- TSLP-DC promote human Tfh differentiation
T follicular helper cells (Tfh) are implicated in various pathological conditions, but how they differentiate in Th2-skewed environments is unknown. Pattarini et al. delineate a pathway for human Tfh differentiation induced by TSLP through OX40L, relevant to atopic dermatitis.
- Splenic neutrophils eradicate S. pneumoniae
The spleen is integral for protection against encapsulated bacteria. Using intravital imaging, Deniset et al. demonstrate that resident neutrophil and macrophage populations in the spleen coordinate the rapid clearance of Streptococcus pneumoniae, ensuring sufficient time for subseqent protective antibody production.
- Genetic landscape of EATL
Enteropathy-associated T cell lymphoma (EATL) is the most common oncologic complication of celiac disease. Moffitt and colleagues identify novel EATL-defining mutations in SETD2, as well as clinically relevant mutations in the JAK-STAT pathway.
- Ultrasensitive detection of IFNα in human diseases
Rodero et al. report the direct quantification of IFNα protein in monogenic interferonopathies, autoimmunity, and infectious disease states, made possible by the combination of digital ELISA and high-affinity autoantibodies isolated from APECED patients, revealing differential levels and cellular sources dependent on underlying pathology.